Pharmacology and Molecular Therapeutics Faculty & Staff
Pharmacology and Molecular Therapeutics
PHA Contact Info
Uniformed Services University of the Health Sciences
Department of Pharmacology and Molecular Therapeutics
4301 Jones Bridge Road
Bethesda, Maryland 20814-4799
Phone: (301) 295-3223
FAX: (301) 295-3220
PHA - Leadership
Regina M Day, Ph.D.
Name: Regina M Day, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Vice Chair
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Email:
Office Phone:
(301) 295-3236
Education
A.B. Smith College, Northampton, MA, USA
Ph.D. Tufts University, Boston, MA, USA
Ph.D. Tufts University, Boston, MA, USA
Biography
Introduction and overview:
My laboratory is dedicated to understanding normal tissue repair processes and how the repair process is altered in fibrotic remodeling. Normal tissue regeneration for wound healing is a critical focus of research for the military as well as for the medical field in general. The long term goal of my laboratory is to understand the mechanism of fibrotic repair and to identify therapeutic agents to prevent and/or treat this disease. The lung provides an excellent model system for investigation, since it is uniquely sensitive to chemicals and radiation that produce well-defined stages of injury, inflammation, attempted repair, and repair failure/remodeling. Lung fibrosis is a progressive disease with no treatments and poor prognosis. Our laboratory uses in vivo animal models and in vitro primary cell cultures to systematically elucidate the mechanisms of tissue regeneration and fibrotic remodeling at the molecular, biochemical, cellular, and tissue levels.
Radiation countermeasures for the lung and hematopoietic systems and radiation biology:
• Radiation countermeasures for both the hematopoietic and lung tissues. Radiation-induced lung injury is a late effect of radiation, whereas hematopoietic injuries are an acute radiation injury. Because of the Department of Defense’s interest in protection against both acute and delayed injuries, we were requested to develop a murine model for both the hematopoietic and pulmonary injuries, and to test radiation countermeasures in both systems. My laboratory developed an animal model system incorporating both hematopoietic and lung radiation injuries. We have determined the mechanism of action of captopril protection in both tissues, as a part of the requirement for radiation countermeasure development under the Animal Rule for the FDA. We are currently expanding our testing of captopril in the minipig model of radiation acute injuries.
• My laboratory developed a cell culture system for studying the molecular mechanisms of radiation-induced senescence in normal (non-transformed, non-immortalized) cells. Our research demonstrated for the first time that normal lung and skin cells primarily undergo accelerated senescence, and not apoptosis, in response to radiation. We identified an early cellular response to radiation is the induction of insulin-like growth factor 1 (IGF-1) and the activation of its receptor (IGF-1R). These novel and provocative observations prompted us to hypothesize that senescence is the precipitating state for radiation pathology.
Hepatocyte growth factor (HGF) signaling for tissue repair and suppression of fibrosis:
• My laboratory has identified novel signaling pathways for HGF-induced normal tissue repair mechanisms. HGF expression is required for normal tissue repair, and HGF can redirect repair away from fibrotic remodeling to induce normal tissue regrowth. To understand how HGF can accomplish this, my research team investigated signal transduction mechanisms for HGF suppression of apoptosis in epithelial and endothelial cells that is induced during fibrosis. We next investigated the mechanisms by which HGF expression is suppressed during fibrotic remodeling. We recently uncovered a novel mechanism by which miRNA regulates HGF mRNA half-life under fibrotic conditions. This research led to the identification of potential novel anti-fibrotic treatment strategies.
• My laboratory developed a synthetic peptide based on other proteins that bind the HGF receptor, MET. The structural complexity of the full length HGF structure has prevented its development as a pharmaceutical agent, and full length HGF has not been successfully produced in sufficient quantities for clinical use. A patent was submitted by the USU/HJF JOTT based on these findings. Our laboratory currently aims to improve the design of this protein, to improve stability and increase receptor affinity.
My laboratory is dedicated to understanding normal tissue repair processes and how the repair process is altered in fibrotic remodeling. Normal tissue regeneration for wound healing is a critical focus of research for the military as well as for the medical field in general. The long term goal of my laboratory is to understand the mechanism of fibrotic repair and to identify therapeutic agents to prevent and/or treat this disease. The lung provides an excellent model system for investigation, since it is uniquely sensitive to chemicals and radiation that produce well-defined stages of injury, inflammation, attempted repair, and repair failure/remodeling. Lung fibrosis is a progressive disease with no treatments and poor prognosis. Our laboratory uses in vivo animal models and in vitro primary cell cultures to systematically elucidate the mechanisms of tissue regeneration and fibrotic remodeling at the molecular, biochemical, cellular, and tissue levels.
Radiation countermeasures for the lung and hematopoietic systems and radiation biology:
• Radiation countermeasures for both the hematopoietic and lung tissues. Radiation-induced lung injury is a late effect of radiation, whereas hematopoietic injuries are an acute radiation injury. Because of the Department of Defense’s interest in protection against both acute and delayed injuries, we were requested to develop a murine model for both the hematopoietic and pulmonary injuries, and to test radiation countermeasures in both systems. My laboratory developed an animal model system incorporating both hematopoietic and lung radiation injuries. We have determined the mechanism of action of captopril protection in both tissues, as a part of the requirement for radiation countermeasure development under the Animal Rule for the FDA. We are currently expanding our testing of captopril in the minipig model of radiation acute injuries.
• My laboratory developed a cell culture system for studying the molecular mechanisms of radiation-induced senescence in normal (non-transformed, non-immortalized) cells. Our research demonstrated for the first time that normal lung and skin cells primarily undergo accelerated senescence, and not apoptosis, in response to radiation. We identified an early cellular response to radiation is the induction of insulin-like growth factor 1 (IGF-1) and the activation of its receptor (IGF-1R). These novel and provocative observations prompted us to hypothesize that senescence is the precipitating state for radiation pathology.
Hepatocyte growth factor (HGF) signaling for tissue repair and suppression of fibrosis:
• My laboratory has identified novel signaling pathways for HGF-induced normal tissue repair mechanisms. HGF expression is required for normal tissue repair, and HGF can redirect repair away from fibrotic remodeling to induce normal tissue regrowth. To understand how HGF can accomplish this, my research team investigated signal transduction mechanisms for HGF suppression of apoptosis in epithelial and endothelial cells that is induced during fibrosis. We next investigated the mechanisms by which HGF expression is suppressed during fibrotic remodeling. We recently uncovered a novel mechanism by which miRNA regulates HGF mRNA half-life under fibrotic conditions. This research led to the identification of potential novel anti-fibrotic treatment strategies.
• My laboratory developed a synthetic peptide based on other proteins that bind the HGF receptor, MET. The structural complexity of the full length HGF structure has prevented its development as a pharmaceutical agent, and full length HGF has not been successfully produced in sufficient quantities for clinical use. A patent was submitted by the USU/HJF JOTT based on these findings. Our laboratory currently aims to improve the design of this protein, to improve stability and increase receptor affinity.
Representative publications, projects, and/or deployments
- 12/2016 – present Vice Chair USUHS School of Medicine Department of Pharmacology and Molecular Therapeutics
- 7/2014- present Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 11/2014 Adjunct Professor Georgetown University School of Medicine Pulmonary, Critical Care, and Sleep Medicine
- 2/2010- 7/2014 Associate Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 7/2004-1/2010 Tenure Track Assistant Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 1/2004-6/2004 Research Assistant Professor Georgetown Univ. School of Medicine Pulmonary, Critical Care, and Sleep Medicine
- 8/1999-12/2004 Research Assistant Professor Tufts-New England Medical Ctr Pulmonary, Critical Care, and Sleep Medicine Div
- Postdoctoral Fellow NIH, NCI, Lab of Cellular, Molecular Biology
Bibliography
- Landauer, M.R., Harvey, A.J., Kaytor, M.D., Day, R.M. (2019) Mechanism and therapeutic window of a genistein nanosuspension to protect against hematopoietic-acute radiation syndrome. J. Radiat. Res. In press.
- McCart, E.A., Lee, Y.H., Jha, J., Mungunsukh, O., Rittase, W.B., Summers, T.A., Muir, J., Day R.M. (2019) Delayed captopril administration mitigates hematopoietic injury in a murine model of total body irradiation. Sci Reports, 9: 2198.
- Bylicky, M.A., Mueller, G.P., Day, R.M. (2019) Radiation resistance of normal human astrocytes: role of non-homologous end joining DNA repair activity. J Radiat Res. 60: 37-50.
- Corey, S.J., Jha, J., McCart, E.A., Rittase, W.B., George, J., Mattapallil, J.J., Mehta, H., Ognoon, M., Bylicky, M.A., Summers, T.A., Day, R.M. (2018) Captopril mitigates splenomegaly and myelofibrosis in the Gata1low murine model of myelofibrosis. J Cell Mol Med, 22: 4274-4282.
- Du, Y., Banas, R.A., McCart, E.A., George, J., Oakley, K., Han, Y., Landauer, M.R., Day, R.M. (2018) Effect of human amnion-derived multipotent progenitor cells on hematopoietic recovery after total body irradiation in C57BL/6 mice. Int J Radiat Res, 16:155-168.
- Zhao*, J., Day*, R.M., Jin, J-Y., Quint, L., Williams, H., Ferguson, C., Yan, L., King, M., Albsheer, A., Matuszak, M., Kong, S-M. (2017) Thoracic radiation-induced pleural effusion and risk factors in patients with lung cancer. Oncotarget, 8: 97623-32.
- McCart, E.A., Lombardini, E., Mog, S.R., Panganiban, R.A.M., Dickson, K.M., Mansur, R.A., Nagy, V., Kim, S-Y., Selwyn, R., Landauer, M.R., Darling, T.N., Day, R.M. (2017) Accelerated senescence in a murine model of radiation-induced skin injury. J Radiat Res, 58: 636-646.
- Brzezniak, C., Oronsky, B., Trepel, J., Summers, T.A. Jr., Cabrales, P., Lee, M.J., Day, R., Jha, S., Caroen, S, Zeman, K, Ferr,y L, Harmer, C, Oronsky, N, Lybeck, M, Lybeck, HE, Brown, JF, Reid, T.R., Carter, C.A. RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor. Case Rep Oncol. 2017;10:276-280.
- Mungunsukh, O., Lee, Y.H., Bottaro, D.P., Day, R.M. (2016) The hepatocyte growth factor isoform NK2 activates motogenesis and survival but not proliferation due to lack of Akt activation. Cell Signal, 28, 1114-23.
- Barshishat-Kupper, M., McCart E.A., Freedy, J.G., Tipton A.J., Nagy V., Kim, S.-Y., Landauer, M.R., Mueller G.P., Day R.M. (2015) Protein oxidation in the lungs of C57BL/6J mice following X-irradiation. Proteomes, 3, 249-265.
Irwin Lucki, Ph.D.
Name: Irwin Lucki, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Professor and Chair
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Neuropharmacology
Antidepressant drugs
Email:
Office Phone:
(301) 295-3248
Education
Education: 1972 B.A. University of Illinois, Psychology
1976 M.A. University of Iowa, Psychology
1979 Ph.D. University of Iowa, Biopsychology
Postgraduate Training:
1979-1981 Postdoctoral Research Fellow, Psychopharmacology Training Program, Department of Psychiatry, University of Pennsylvania
1976 M.A. University of Iowa, Psychology
1979 Ph.D. University of Iowa, Biopsychology
Postgraduate Training:
1979-1981 Postdoctoral Research Fellow, Psychopharmacology Training Program, Department of Psychiatry, University of Pennsylvania
Biography
Selected from 180 publications:
Cryan, J.F., Valentino, R.J. and Lucki, I. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neuroscience and Biobehavioral Reviews, 2005, 29:547-569.
Valentino, R.J., Lucki, I. and Van Bockstaele, E. Corticotropin-releasing factor in the dorsal raphe nucleus: Linking stress coping and addiction. Brain Research, 2010, 1314:29-37. PMC2819581
Ho, N., Sommers, M.S. and Lucki, I. Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression. Neuroscience and Biobehavioral Reviews, 2013, 37:1346-1362. PMC3788092
Browne, C.A. and Lucki, I. Mechanisms mediating the antidepressant-like Lucki, I. The spectrum of behaviors influenced by serotonin. Biological Psychiatry, 1998, 44:151-162.
Page, M.E., Cryan, J.F., Sullivan, A., Dalvi, A. and Lucki, I. Behavioral and neurochemical effects of EMD 68843: A combined selective inhibitor of serotonin reuptake and partial 5-HT1A receptor agonist. Journal of Pharmacology and Experimental Therapeutics, 2002, 302:1-8.
Carr, G.V. and Lucki, I. The role of serotonin receptor subtypes in treating depression: A review of animal studies. Psychopharmacology, 2011, 213:265-287. PMC3374933
Carr, G.V., Schechter, L.E. and Lucki, I. Antidepressant and anxiolytic effects of
selective 5-HT6 receptor agonists in rats. Psychopharmacology, 2011, 213:499-507. PMC2910165
effects of ketamine: Screening for fast-acting novel antidepressants. Frontiers in Neuropharmacology, 2013, 4:161, 1-18. PMC3873522.
Mayorga, A.J., Dalvi, A., Page, M.E., Zimov-Levinson, S., Hen R. and Lucki, I. Antidepressant-like behavioral effects in 5-HT1A and 5-HT1B receptor mutant mice. Journal of Pharmacology and Experimental Therapeutics, 2001, 298:1101-1107.
Cryan, J.F., O’Leary, O.F., Jin, S.-H., Friedland, J.C., Ouyang, M., Hirsch, B.R., Page, M.E., Dalvi, A., Thomas, S.A. and Lucki, I. Norepinephrine deficient mice lack responses to antidepressant drugs, including SSRIs. Proceedings of the National Academy of Sciences, 2004, 101:8186-8191.
O’Leary, O.F., Bechtholt, A.J., Crowley, J.J., Valentino, R.J. and Lucki, I. The role of noradrenergic tone in the dorsal raphe nucleus of the mouse in the acute behavioral effects of antidepressant drugs. European Neuropsychopharmacology, 2007, 17:215-226.
Balu, D.T., Turner, J.R., Brookshire, B.R., Hill, T.E., Blendy, J.A. and Lucki, I. Brain monoamines and responses to antidepressant drugs in MRL/MpJ versus C57BL/6J and mice. Neuropharmacology, 2013, 67:503-510. PMC437180
Cryan, J.F., Markou, A. and Lucki, I. Assessing antidepressant-like activity in laboratory animals: Recent developments and future needs. Trends in Pharmacological Sciences, 2002, 23(5): 238-245.
Crowley, J.J. and Lucki, I. Opportunities to discover genes regulating depression and antidepressant response from rodent behavioral genetics. Current Pharmaceutical Design, 11:157-169, 2005.
Bechtholt, A.J., Valentino, R.J. and Lucki, I. Overlapping and distinct brain regions associated
with the anxiolytic effects of chlordiazepoxide and chronic fluoxetine. Neuropsychopharmacology, 2008, 33:2117-2130.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Price, M. L., Curtis, A.L., Kirby, L.G., Valentino, R.J. and Lucki, I. Biphasic effects of corticotropin-releasing factor on brain serotonergic activity. Neuropsychopharmacology, 1998, 18:492-502.
Price, M.L. and Lucki, I. Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor. Journal of Neuroscience, 2001, 21:2833-2841.
Howard, O., Carr, G.V., Hill, T.E., Valentino, R.J. and Lucki, I. Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin. Psychopharmacology, 2008, 199:569-82. PMC2744742
Snyder, K.P., Hill-Smith, T.E., Lucki, I. and Valentino, R.J. Corticotropin-releasing factor in the rat dorsal raphe nucleus promotes different forms of behavioral flexibility depending on social stress history. Neuropsychopharmacology, 2015, 40:2517-25. PMCID in process.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Falcon, E., Maier, K., Robinson, S.A. and Lucki, I. Effects of buprenorphine on behavioral tests for antidepressant and anxiolytic drugs in mice. Psychopharmacology, 2015, 232:907-915. PMC4326609
Browne, C.A., van Nest, D. and Lucki, I. Antidepressant-like effects of buprenorphine in rats are strain dependent. Behavioural Brain Research, 2015, 278:385-392. PMC4382376
Falcon, E., Browne, C.A., Leon, R.M., Fleites, V.C., Sweeney, R., Kirby, L.G. and Lucki, I. Antidepressant-like effects of buprenorphine are mediated by kappa opioid receptors. Neuropsychopharmacology, 2016, 41(9):2344-2351. PMC4946065
A full bibliography of over 170 peer-reviewed publications is available at: http://www.ncbi.nlm.nih.gov/sites/myncbi/irwin.lucki.1/bibliography/45296221/public/?sort=date&direction=ascending.
Cryan, J.F., Valentino, R.J. and Lucki, I. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neuroscience and Biobehavioral Reviews, 2005, 29:547-569.
Valentino, R.J., Lucki, I. and Van Bockstaele, E. Corticotropin-releasing factor in the dorsal raphe nucleus: Linking stress coping and addiction. Brain Research, 2010, 1314:29-37. PMC2819581
Ho, N., Sommers, M.S. and Lucki, I. Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression. Neuroscience and Biobehavioral Reviews, 2013, 37:1346-1362. PMC3788092
Browne, C.A. and Lucki, I. Mechanisms mediating the antidepressant-like Lucki, I. The spectrum of behaviors influenced by serotonin. Biological Psychiatry, 1998, 44:151-162.
Page, M.E., Cryan, J.F., Sullivan, A., Dalvi, A. and Lucki, I. Behavioral and neurochemical effects of EMD 68843: A combined selective inhibitor of serotonin reuptake and partial 5-HT1A receptor agonist. Journal of Pharmacology and Experimental Therapeutics, 2002, 302:1-8.
Carr, G.V. and Lucki, I. The role of serotonin receptor subtypes in treating depression: A review of animal studies. Psychopharmacology, 2011, 213:265-287. PMC3374933
Carr, G.V., Schechter, L.E. and Lucki, I. Antidepressant and anxiolytic effects of
selective 5-HT6 receptor agonists in rats. Psychopharmacology, 2011, 213:499-507. PMC2910165
effects of ketamine: Screening for fast-acting novel antidepressants. Frontiers in Neuropharmacology, 2013, 4:161, 1-18. PMC3873522.
Mayorga, A.J., Dalvi, A., Page, M.E., Zimov-Levinson, S., Hen R. and Lucki, I. Antidepressant-like behavioral effects in 5-HT1A and 5-HT1B receptor mutant mice. Journal of Pharmacology and Experimental Therapeutics, 2001, 298:1101-1107.
Cryan, J.F., O’Leary, O.F., Jin, S.-H., Friedland, J.C., Ouyang, M., Hirsch, B.R., Page, M.E., Dalvi, A., Thomas, S.A. and Lucki, I. Norepinephrine deficient mice lack responses to antidepressant drugs, including SSRIs. Proceedings of the National Academy of Sciences, 2004, 101:8186-8191.
O’Leary, O.F., Bechtholt, A.J., Crowley, J.J., Valentino, R.J. and Lucki, I. The role of noradrenergic tone in the dorsal raphe nucleus of the mouse in the acute behavioral effects of antidepressant drugs. European Neuropsychopharmacology, 2007, 17:215-226.
Balu, D.T., Turner, J.R., Brookshire, B.R., Hill, T.E., Blendy, J.A. and Lucki, I. Brain monoamines and responses to antidepressant drugs in MRL/MpJ versus C57BL/6J and mice. Neuropharmacology, 2013, 67:503-510. PMC437180
Cryan, J.F., Markou, A. and Lucki, I. Assessing antidepressant-like activity in laboratory animals: Recent developments and future needs. Trends in Pharmacological Sciences, 2002, 23(5): 238-245.
Crowley, J.J. and Lucki, I. Opportunities to discover genes regulating depression and antidepressant response from rodent behavioral genetics. Current Pharmaceutical Design, 11:157-169, 2005.
Bechtholt, A.J., Valentino, R.J. and Lucki, I. Overlapping and distinct brain regions associated
with the anxiolytic effects of chlordiazepoxide and chronic fluoxetine. Neuropsychopharmacology, 2008, 33:2117-2130.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Price, M. L., Curtis, A.L., Kirby, L.G., Valentino, R.J. and Lucki, I. Biphasic effects of corticotropin-releasing factor on brain serotonergic activity. Neuropsychopharmacology, 1998, 18:492-502.
Price, M.L. and Lucki, I. Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor. Journal of Neuroscience, 2001, 21:2833-2841.
Howard, O., Carr, G.V., Hill, T.E., Valentino, R.J. and Lucki, I. Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin. Psychopharmacology, 2008, 199:569-82. PMC2744742
Snyder, K.P., Hill-Smith, T.E., Lucki, I. and Valentino, R.J. Corticotropin-releasing factor in the rat dorsal raphe nucleus promotes different forms of behavioral flexibility depending on social stress history. Neuropsychopharmacology, 2015, 40:2517-25. PMCID in process.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Falcon, E., Maier, K., Robinson, S.A. and Lucki, I. Effects of buprenorphine on behavioral tests for antidepressant and anxiolytic drugs in mice. Psychopharmacology, 2015, 232:907-915. PMC4326609
Browne, C.A., van Nest, D. and Lucki, I. Antidepressant-like effects of buprenorphine in rats are strain dependent. Behavioural Brain Research, 2015, 278:385-392. PMC4382376
Falcon, E., Browne, C.A., Leon, R.M., Fleites, V.C., Sweeney, R., Kirby, L.G. and Lucki, I. Antidepressant-like effects of buprenorphine are mediated by kappa opioid receptors. Neuropsychopharmacology, 2016, 41(9):2344-2351. PMC4946065
A full bibliography of over 170 peer-reviewed publications is available at: http://www.ncbi.nlm.nih.gov/sites/myncbi/irwin.lucki.1/bibliography/45296221/public/?sort=date&direction=ascending.
Representative publications, projects, and/or deployments
- 2007 - present, Principal Field Editor, Psychopharmacology
- 1995 - present, Editorial Advisory Board, Neuropsychopharmacology
- 2014 – present, Editorial Advisory Board, Neurobiology of Stress
- Buprenorphine for Depression and Anxiety.PI. NIMH, R01 MH92412, 2012-2018. Total direct costs = $1,250,000. The goal of this grant is to examine animal models supporting the development of buprenorphine for the clinical treatment of depression and anxiety.
- Kappa Receptor Antagonists as Rapid Acting Antidepressants. PI. NIMH, R01 MH105623, 2016-2020. Total direct costs = $1,000,000. The goal of this grant is to study animal models supporting the development of novel kappa receptor antagonists for the clinical treatment of mood disorders.
- Training Program in Neuropsychopharmacology. NIMH, T32 MH14654-34-38, 1978-2021. I was Training Program Director at the University of Pennsylvania 1992-2016.
- Regulation of Hippocampal Neurogenesis by Antidepressants. PI. NIMH, R01 MH86599, 2009-2015.
- Biology of Serotonin in Brain; Program Project Grant: Irwin Lucki, Ph.D., Program Director (1994-2007). NIMH, PO1-MH-48125.
- Regulation of Neurogenesis by Stress and Antidepressants. Program Director. National Cooperative Drug Discovery Group involving University of Pennsylvania and Wyeth Neuroscience. U01-MH 72832, 2005-2009.
Bibliography
- 2016- present Professor (with tenure) and Chair, Department of Pharmacology and Molecular Therapeutics, Uniformed University of the Health Sciences, Bethesda MD
- 2016-present Professor, Department of Psychiatry, Uniformed University of the Health Sciences, Bethesda MD
- 1996-2016 Professor of Psychology in Psychiatry (with tenure), Depts. of Psychiatry and Pharmacology, University of Pennsylvania, Philadelphia PA
- 1990-1996 Associate Professor of Psychology in Psychiatry (with tenure), Depts. of Psychiatry and Pharmacology, University of Pennsylvania, Philadelphia PA
- 1989-1990 Assistant Professor, Department of Pharmacology, University of Pennsylvania, Philadelphia PA
- 1984-1990 Assistant Professor of Psychology in Psychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia PA
- 1981-1984 Research Associate, Department of Psychiatry, University of Pennsylvania, Philadelphia PA
PHA - Neuropharmacology
Brian M. Cox, Ph.D.
Name: Brian M. Cox, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Professor of Pharmacology & Neuroscience
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Neuropharmacology - opiate drugs & substance use disorderds
Traumatic brain injury - mechanisms & biomarkers
Email:
Office Phone:
(301) 295-3260
Education
Ph.D. in Pharmacology, St. Mary's Hospital Medical School, University of London, London, United Kingdom, 1965
B.Sc. in Pharmacolopy, Chelsea College of Science & Technology, University of London, London, United Kingdom, 1962
B.Sc. in Pharmacolopy, Chelsea College of Science & Technology, University of London, London, United Kingdom, 1962
Biography
Dr. Cox is currently Professor of Pharmacology and Neuroscience at the Uniformed Services University (USU) in Bethesda MD. He received his initial training in pharmacology from Chelsea College of Science and Technology in London, UK, and received a Ph.D. in Pharmacology from St. Mary's Hospital Medical School, University of London, UK. After teaching pharmacology to pharmacy and science students at Chelsea College of Science and Technology of the University of London for eight years, he became a visiting scientist in the Department of Pharmacology at Stanford University, and was appointed Consulting Associate Professor of Pharmacology at Stanford in 1978. Concurrently, he served as Laboratory Research Group Director and then Associate Director for Research for the Addiction Research Foundation in Palo Alto, CA. In 1981, Dr. Cox moved to his current position at USU, where he served as chair of the Department of Pharmacology from 1995 until 2007. He currently also serves as an Assistant Dean for Graduate Education at USU.
For most of his career Dr. Cox's research has focused on characterizing the receptors utilized by opiate drugs and their endogenous ligands, and in defining potential physiological and pathophysiological roles for endogenous opioids and other neuropeptides. His lab is currently studying factors affecting peptide and receptor expression, and changes at the cellular level induced by drugs of abuse, severe stress, or neural injury. He now leads the Biomarkers Group of the USU/NIH Center for Neuroscience and Regenerative Medicine, evaluating neurochemical mechanisms underlying traumatic brain injury and potential biomarkers for TBI.
Dr. Cox has been a member of the American Society for Pharmacology and Experimental Therapeutics (ASPET) since 1976. He served as Secretary/Treasurer of (1997-2000), and was elected President of ASPET for 2009-2010. He chaired the ASPET Board of Publications Trustees from 2002-2007. He has served on the Editorial Boards of the Journal of Pharmacology and Experimental Therapeutics (1998 – present), Molecular Pharmacology (1981-1994), and Molecular Interventions (2000-2002). Dr. Cox was a member of the ASPET Scientific Program Committee from 1986-1990 and Chaired the Program Committee from 1990-1996. He served as ASPET’s representative to the Experimental Biology Program Committee from 1991-1994 and served on the Experimental Biology Board from 1996-1999 (as Chairman for 1998-1999). He is currently serving a second term as a member of the Board of Directors of the Federation of American Societies of Experimental Biology.
Dr. Cox was the ASPET representative to the International Advisory Committee for the 1998 International Union of Pharmacology (IUPHAR) Congress in Munich, Germany, and chaired the IUPHAR World Congress of Pharmacology Scientific Program Committee for the 2002 meeting, held in San Francisco, CA. He is also a member of the British Pharmacological Society, the Society for Neuroscience, the AAAS, the American Society for Neurochemistry, and the International Narcotics Research Conference (for which he served as President from 1994-1998).
For most of his career Dr. Cox's research has focused on characterizing the receptors utilized by opiate drugs and their endogenous ligands, and in defining potential physiological and pathophysiological roles for endogenous opioids and other neuropeptides. His lab is currently studying factors affecting peptide and receptor expression, and changes at the cellular level induced by drugs of abuse, severe stress, or neural injury. He now leads the Biomarkers Group of the USU/NIH Center for Neuroscience and Regenerative Medicine, evaluating neurochemical mechanisms underlying traumatic brain injury and potential biomarkers for TBI.
Dr. Cox has been a member of the American Society for Pharmacology and Experimental Therapeutics (ASPET) since 1976. He served as Secretary/Treasurer of (1997-2000), and was elected President of ASPET for 2009-2010. He chaired the ASPET Board of Publications Trustees from 2002-2007. He has served on the Editorial Boards of the Journal of Pharmacology and Experimental Therapeutics (1998 – present), Molecular Pharmacology (1981-1994), and Molecular Interventions (2000-2002). Dr. Cox was a member of the ASPET Scientific Program Committee from 1986-1990 and Chaired the Program Committee from 1990-1996. He served as ASPET’s representative to the Experimental Biology Program Committee from 1991-1994 and served on the Experimental Biology Board from 1996-1999 (as Chairman for 1998-1999). He is currently serving a second term as a member of the Board of Directors of the Federation of American Societies of Experimental Biology.
Dr. Cox was the ASPET representative to the International Advisory Committee for the 1998 International Union of Pharmacology (IUPHAR) Congress in Munich, Germany, and chaired the IUPHAR World Congress of Pharmacology Scientific Program Committee for the 2002 meeting, held in San Francisco, CA. He is also a member of the British Pharmacological Society, the Society for Neuroscience, the AAAS, the American Society for Neurochemistry, and the International Narcotics Research Conference (for which he served as President from 1994-1998).
Representative publications, projects, and/or deployments
- Assistant Dean for Graduate Education, Uniformed Services University, Bethesda MD 20814, since 2014
- Director, Biospecimen Repository, Center for Neuroscience & Regenerative Medicine, Uniformed Services University, Bethesda MD 20814, since 2009
- Professor of Pharmacology, Uniformed Services University, Bethesda MD 20814, since 1981
- Associate Director for Research, Addiction Research Foundation, Stanford, California, 94305, 1977-1981
- Consulting Associate Professor of Pharmacology, Stanford University, Stanford CA, 94305. 1978 - 1981
- Research Associate, Director, Laboratory Research Group, Addiction Research Foundation, Stanford, California, 94305, 1973-1977
- Lecturer (British System) in Pharmacology, Chelsea College, University of London, London, United Kingdom, 1965-1973
- Nicholas Research Fellow, St. Mary's Hospital Medical School, University of London, London, United Kingdom, 1962-1965
Bibliography
- Cox, B.M. and Weinstock, M. Quantitative studies of the antagonism by nalorphine of some of the actions of morphine-like analgesic drugs. Br. J. Pharmac. 22:289-300, 1964.
- Cox, B.M. and Osman, O.H. Inhibition of the development of tolerance to morphine in rats by drugs which inhibit ribonucleic acid or protein synthesis. Br. J. Pharmac. 38:157-170, 1970.
- Cox, B.M., Opheim, K., Teschemacher, H.-J. and Goldstein, A. A peptide-like substance from pituitary that acts like morphine. 2. Purification and properties. Life Sci. 16:1777-1782, 1975.
- Goldstein, A., Cox, B.M., Klee, W.A., and Nirenberg, M. Endorphin from pituitary inhibits cyclic AMP formation in homogenates of neuroblastoma X glioma hybrid cells. Nature 265:362-363, 1977.
- Whitnall, M.H., Gainer, H., Cox, B.M. and Molineaux, C.J. Dynorphin A(1-8) is contained within vasopressin neurosecretory vasicles in rat pituitary. Science 222:1137-1139, 1983.
- Faden, A.I., Molineaux, C.J., Rosenberger, J.G., Jacobs, T.P. and Cox, B.M. Endogenous opioid immunoreactivity in rat spinal cord following traumatic injury. Ann. Neurol. 17:386-390, 1985.
- Werling, L.L., Puttfarcken, P.S. and Cox, B.M. Multiple agonist-affinity states of opioid receptors: regulation of binding by guanyl nucleotides in guinea pig cortical, NG108-15, and 7315c cell membranes. Mol. Pharmacol. 33:423-431, 1988.
- Marti M, Mela F, Fantin M, Zucchini S, Brown JM, Witta J, Di Benedetto M, Buzas B, Reinscheid RK, Salvadori S, Guerrini R, Romualdi P, Candeletti S, Simonato M, Cox BM and Morari M. Blockade of nociceptin/orphanin FQ transmission attenuates symptoms and neurodegeneration associated with Parkinson’s disease. J. Neuroscience 25: 9591-9601, 2005.
- Authement ME, Kodangatil JN, Gouty S, Rusnak M, Symes AJ, Cox BM, Nugent F. Histone deacetylase inhibition rescues maternal deprivation-induced GABAergic metaplasticity through restoration of AKAP signaling. Neuron 86: 1240-1252, 2015.
- Authement M, Kassis H, Langlois L, Gouty S, Dacher M, Sheopard R, Cox BM & Nugent FS. Morphine-induced synaptic abnormalities in the VTA are reversed by HDAC inhibition. J. Neurophysiol. 116(3): 1093-1103, 2016.
Kari A. Johnson, PhD
Name: Kari A. Johnson, PhD
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Assistant Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Synaptic plasticity, action control, G protein-coupled receptors, alcohol use disorders
Email:
Office Phone:
(301) 295-3907
Education
B.A., Biology, Religious Studies, University of Pennsylvania, Philadelphia, PA
Ph.D., Pharmacology, Vanderbilt University, Nashville, TN
Postdoctoral Training, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD
Ph.D., Pharmacology, Vanderbilt University, Nashville, TN
Postdoctoral Training, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD
Biography
Research in the Johnson Laboratory focuses on physiological adaptations in basal ganglia circuits that occur following chronic alcohol exposure in mice, and how these adaptations relate to cognitive impairments caused by alcohol. We are particularly interested in roles of G protein-coupled receptors in modulating neurotransmission at relevant synapses and how these receptors modify behavior under both normal and pathological conditions.
Bibliography
Biosketch Link:
- Kupferschmidt DA, Augustin SM, Johnson KA, Lovinger DM (2019) Active zone proteins RIM1αβ are required for normal corticostriatal plasticity and action control. Journal of Neuroscience. Feb 20;39(8):1457-1470.
- Mateo Y, Johnson KA, Covey DP, Atwood BK, Wang HL, Zhang S, Gildish I, Cachope R, Bellocchio L, Guzmán M, Morales M, Cheer JF, Lovinger DM (2017) Endocannabinoid actions on cortical terminals orchestrate local modulation of dopamine release in the nucleus accumbens. Neuron. 96(5):1112-1126.
- Johnson KA, Mateo Y, Lovinger DM (2017) Metabotropic glutamate receptor 2 modulates thalamically-driven glutamate and dopamine release in the dorsal striatum. Neuropharmacology. 117:114-123.
- Johnson KA, Lovinger DM (2016) Presynaptic G protein-coupled receptors: Gatekeepers of addiction? Frontiers in Cellular Neuroscience. Nov 11;10:264.
- Yin S, Noetzel MJ, Johnson KA, Zamarano R, Gregory KJ, Conn PJ, Niswender CM (2014) Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS. Journal of Neuroscience. 34(1):79-94.
- Johnson KA*, Jones CK*, Tantawy MN, Bubser M, Marvanova M, Ansari MS, Baldwin RM, Conn PJ, Niswender CM (2013) The metabotropic glutamate receptor agonist (S)-3,4-DCPG reverses motor deficits in prolonged but not acute models of Parkinson’s disease. Neuropharmacology. 66:187-95. *These authors contributed equally to this work.
- Johnson KA, Niswender CM, Conn PJ, Xiang Z (2011) Activation of group II metabotropic glutamate receptors induces long-term depression of excitatory synaptic transmission in the substantia nigra pars reticulata. Neuroscience Letters. 504(2):102-6.
- Johnson KA, Conn PJ (2011) Metabotropic glutamate receptor-dopamine interactions in the basal ganglia motor circuit. Glutamate-dopamine interactions in the basal ganglia. Ed. Susan Jones. Boca Raton: CRC Press. pp. 1-29.
- Johnson KA, Conn PJ, Niswender CM (2009) Glutamate receptors as therapeutic targets for Parkinson’s disease. CNS and Neurological Disorders – Drug Targets. 8(6):475-91.
- Niswender CM*, Johnson KA*, Weaver CD, Jones CK, Xiang Z, Luo Q, Rodriguez AL, Marlo JE, de Paulis T, Thompson AD, Days EL, Nalywajko T, Austin CA, Williams MB, Ayala JE, Williams R, Lindsley CW, Conn PJ (2008) Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4. Molecular Pharmacology. 74(5):1345-58. *These authors contributed equally to this work.
Fereshteh S. Nugent, Ph.D.
Name: Fereshteh S. Nugent, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
USU faculty
Faculty Rank:
Associate Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Synaptic plasticity, Reward Pathway, Addiction Neuorpsychiatric Disorders
Novel Anidepressants
Email:
Office Phone:
(301) 295-3243
Department Website:
Education
Ph.D., Neurophysiology, Tarbiat Modarres University, Tehran, Iran, 2003
Postdoctoral, Neuroscience, Brown University
Postdoctoral, Neuroscience, Brown University
Biography
Synaptic Plasticity of the Reward Pathway
Since the discovery of synaptic plasticity as the cellular correlate of learning and memory, strong overlaps between neural and cellular substrates of learning, drug addiction and stress-related disorders have been recognized. Yet it remains a major challenge to identify the neural circuits and synaptic mechanisms contributing to abnormalities in dopamine signaling induced by addictive drugs and adverse early life experiences. The major focus of my laboratory is the elucidation of synaptic mechanisms underlying reward learning, drug addiction and neuropsychiatric disorders such as depression, with particular emphasis on the midbrain dopamine system originating from the ventral tegmental area (VTA) and its control by the lateral habenula (LHb). Research in our laboratory also explores effects of severe early life stress on synaptic transmission and plasticity of distinct VTA dopamine circuits to identify the neural circuits and molecular mechanisms contributing to abnormalities in dopamine signaling induced by adverse early life experiences. To achieve these goals, we use a combination of immunohistochemical, biochemical, epigenetic, electrophysiological and behavioral techniques. We expect that identifying novel epigenetic mechanisms in the regulation of synaptic plasticity and memory formation in midbrain dopamine circuits will point to new directions in pharmacotherapy for drug addiction and stress-related disorders.
Selected Publications
Authement M.E., L. L. D., Shepard R.D., Browne C.A., Lucki L., Kassis H., Nugent F.S., A role for corticotrophin releasing factor signaling in the lateral habenula and its modulation by early life stress, Science Signaling, 11(520) (2018), Featured as the cover story
Summary: http://stke.sciencemag.org/cgi/content/summary/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Abstract: http://stke.sciencemag.org/cgi/content/abstract/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Reprint: http://stke.sciencemag.org/cgi/reprint/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Full text: http://stke.sciencemag.org/cgi/content/full/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Langlois, L.D. and Nugent F.S. Opiates and plasticity in ventral tegmental area, Invited Review, ACS Chemical Neuroscience, 20;8(9):1830-1838 (2017)
Authement M.E., Kodangattil J.N.,Gouty,S., Rusnak, M., Symes A.J., Cox B.M., and Nugent F.S., Histone deacetylase inhibition rescues maternal deprivation-induced GABAergic metaplasticity through restoration of AKAP signaling, Neuron, 86: 1240–1252 (2015)
Kodangattil J.N., Dacher M.A., Authement, M.E. and Nugent F.S., Spike timing-dependent plasticity at GABAergic synapses in the Ventral tegmental area. Journal of Physiology, 591.19: 4699-710 (2013)
Dacher, M. A., Gouty, S., Dash, S., Cox, B.M., and Nugent, F.S., A-kinase anchoring protein-calcineurin signaling in long-term depression of GABAergic synapses, Journal of Neuroscience, 33:2650-60 (2013)
Nugent, F.S., Penick, E.C., Kauer, J.A., Opiates block long-term potentiation of GABAergic synapses. Nature, 466: 1086-1095 (2007)
Postdoctoral Fellows: Dr. Ludovic Langlois
Graduate Students: Ryan Shepard
Lab Alumni: Dr. Matthieu Dacher (Université Pierre et Marie Curie, France), Dr. Jayaraj N. Kodangattil, Dr. Haifa Kassis, Dr. Michael Authement (NIAAA) and Steven Dash
Since the discovery of synaptic plasticity as the cellular correlate of learning and memory, strong overlaps between neural and cellular substrates of learning, drug addiction and stress-related disorders have been recognized. Yet it remains a major challenge to identify the neural circuits and synaptic mechanisms contributing to abnormalities in dopamine signaling induced by addictive drugs and adverse early life experiences. The major focus of my laboratory is the elucidation of synaptic mechanisms underlying reward learning, drug addiction and neuropsychiatric disorders such as depression, with particular emphasis on the midbrain dopamine system originating from the ventral tegmental area (VTA) and its control by the lateral habenula (LHb). Research in our laboratory also explores effects of severe early life stress on synaptic transmission and plasticity of distinct VTA dopamine circuits to identify the neural circuits and molecular mechanisms contributing to abnormalities in dopamine signaling induced by adverse early life experiences. To achieve these goals, we use a combination of immunohistochemical, biochemical, epigenetic, electrophysiological and behavioral techniques. We expect that identifying novel epigenetic mechanisms in the regulation of synaptic plasticity and memory formation in midbrain dopamine circuits will point to new directions in pharmacotherapy for drug addiction and stress-related disorders.
Selected Publications
Authement M.E., L. L. D., Shepard R.D., Browne C.A., Lucki L., Kassis H., Nugent F.S., A role for corticotrophin releasing factor signaling in the lateral habenula and its modulation by early life stress, Science Signaling, 11(520) (2018), Featured as the cover story
Summary: http://stke.sciencemag.org/cgi/content/summary/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Abstract: http://stke.sciencemag.org/cgi/content/abstract/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Reprint: http://stke.sciencemag.org/cgi/reprint/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Full text: http://stke.sciencemag.org/cgi/content/full/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Langlois, L.D. and Nugent F.S. Opiates and plasticity in ventral tegmental area, Invited Review, ACS Chemical Neuroscience, 20;8(9):1830-1838 (2017)
Authement M.E., Kodangattil J.N.,Gouty,S., Rusnak, M., Symes A.J., Cox B.M., and Nugent F.S., Histone deacetylase inhibition rescues maternal deprivation-induced GABAergic metaplasticity through restoration of AKAP signaling, Neuron, 86: 1240–1252 (2015)
Kodangattil J.N., Dacher M.A., Authement, M.E. and Nugent F.S., Spike timing-dependent plasticity at GABAergic synapses in the Ventral tegmental area. Journal of Physiology, 591.19: 4699-710 (2013)
Dacher, M. A., Gouty, S., Dash, S., Cox, B.M., and Nugent, F.S., A-kinase anchoring protein-calcineurin signaling in long-term depression of GABAergic synapses, Journal of Neuroscience, 33:2650-60 (2013)
Nugent, F.S., Penick, E.C., Kauer, J.A., Opiates block long-term potentiation of GABAergic synapses. Nature, 466: 1086-1095 (2007)
Postdoctoral Fellows: Dr. Ludovic Langlois
Graduate Students: Ryan Shepard
Lab Alumni: Dr. Matthieu Dacher (Université Pierre et Marie Curie, France), Dr. Jayaraj N. Kodangattil, Dr. Haifa Kassis, Dr. Michael Authement (NIAAA) and Steven Dash
Ying-Hong Feng, M.D., Ph.D
Name: Ying-Hong Feng, M.D., Ph.D
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Dr.
Faculty Rank:
Associate Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Receptor structure-function & signaling; Epigenome editing & transcription regulation
Translational research in neurodegenerative diseases, mood disorder, cancer, diabetes, and cardiovascular diseases
Email:
Office Phone:
(301) 295-3232
Department Website:
Education
1978-1983, M.D., Wuhan University School of Medicine, Wuhan, China
1990-1994, Ph.D., Biochemistry, University of Oxford, Oxford, UK
1994-1997, Postdoctoral, Molecular Cardiology, Cleveland Clinic Foundation
1990-1994, Ph.D., Biochemistry, University of Oxford, Oxford, UK
1994-1997, Postdoctoral, Molecular Cardiology, Cleveland Clinic Foundation
Biography
Feng’s lab has three research programs. The first is about crosstalk signaling of receptors in the form of receptor dimerization in pathophysiology such as vascular inflammation, metabolism (type 2 diabetes), pain (silent myocardial ischemia), depression, immunosuppression, cancer progression, and etc. The second is about translational research on neurodegenerative diseases and cancer with focus on novel splicing variants, of critical genes that are known to play an important role in depression, neurodegeneration, neuroregeneration, exosome biology, tumorigenesis, and cancer progression. The last is to develop novel technologies for genome editing and epigenome editing.
Representative publications, projects, and/or deployments
- Feng YH, Li X, Zeng R, Gorodeski GI. Endogenously Expressed Truncated P2X7 Receptor Lacking the C-Terminus is Preferentially Upregulated in Epithelial Cancer Cells and Fails to Mediate Ligand-Induced Pore Formation and Apoptosis. Nucleosides Nucleotides Nucleic Acids. 25:1271-6 (2006)
- Feng YH, Li X, Zeng R, Gorodeski GI. Endogenously expressed truncated P2X7 receptor lacking the C-terminus is preferentially upregulated in epithelial cancer cells and fails to mediate ligand-induced pore formation and apoptosis. Nucleosides Nucleotides Nucleic Acids. 25(9-11):1271-6 (2006)
- Chen M, Wang T, Liao ZX, Pan XL, Feng YH, Wang H. Nicotine-induced prenatal overexposure to maternal glucocorticoid and intrauterine growth retardation in rat. Exp Toxicol Pathol. 59: 245-51 (2007)
- 30. Zhang X, Wang G, Dupre DJ, Feng Y, Robitaille M, Lazartigues E, Feng YH, Hebert TE, Wu G. Rab1 GTPase and dimerization in the cell surface expression of angiotensin II type 2 receptor. J Pharmacol Exp Ther. 330(1):109-17 (2009)
- 31. Guo J, Li ZC and Feng YH. Expression and activation of the reprogramming transcription factors. Biochem Biophys Res Commun. 390(4):1081-6 (2009)
- 32. Zhang J, Villacorta L, Chang L, Fan Z, Hamblin M, Zhu T, Chen CS, Cole MP, Schopfer FJ, Deng CX, Garcia-Barrio MT, Feng YH, Freeman BA, Chen YE. Nitrated oleic acid inhibits Angiotensin II-induced hypertension. Circ Res, 107(4):540-8 (2010)
- 34. Day RD, Lee YH, Han L, Kim YC, Feng YH. Angiotensin II activates AMPK for execution of apoptosis through energy-dependent and -independent mechanisms. Am J Physiol Lung Cell Mol Physiol, 301(5):L772-81 (2011)
- 35. Wang TT, Chen M, Liu L, Cheng H, Yan YE, Feng YH*, Wang H. Nicotine induces a single CpG methylation in the StAR promoter: a potential mechanism for reduced StAR expression and cortisol production. Toxicol and Applied Pharmacol. 257(3):328-37 (2011) *Co-senior author
- 37. Wang H, Yin H, Yan F, Sun M, Du L, Peng W, Li Q, Feng Y, Zhou Y. Folate-mediated mitochondrial targeting with doxorubicin-polyrotaxane nanoparticles overcomes multidrug resistance. Oncotarget. 6(5):2827-42 (2015).
- 38. Li K, Pang J, Cheng H, Wei-Peng Liu WP, Chen MK, Yun Luo Y, Di JM, Zhang H, Huang WT, Li LY, Shao CK, Feng YH*, Gao X. Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase. Oncotarget. 6(12):10030-44 (2015) *Co-senior author
Bibliography
- Feng YH, Saad Y and Karnik SS. Reversible Inactivation of AT2 Angiotensin II Receptor from Cysteine-Disulfide Bond Exchange. FEBS Letters 484, 133-138 (2000)
- Feng YH, Sun Y, and Douglas JG. G??-Independent Constitutive Association of Gs? with SHP-1 and Angiotensin II Receptor AT2 Is Essential in AT2-mediated Activation of SHP-1. Proc. Natl. Acad. Sci. USA 99:12049-12054 (2002)
- Wang Q, Li X, Wang L, Feng YH, Zeng R, Gorodeski GI. Anti-apoptotic effects of estrogen in normal and in cancer human cervical epithelial cells. Endocrinology 145:5568-79 (2004)
- Wang Q, Wang L, Feng YH, Li X, Zeng R, Gorodeski GI. P2X7-receptor-mediated apoptosis of human cervical epithelial cells. Am J Physiol Cell Physiol. 287:C1349-58 (2004)
- Wang L, Feng YH, Gorodeski GI. EGF facilitates epinephrine inhibition of P2X7-receptor pore formation by modulating 2-adrenoceptor internalization and recycling: a signaling network. Endocrinology 146:164-74 (2005)
- Feng YH, Zhou LY, Sun Y, and Douglas JG. Functional Diversity of AT2 Receptor Orthologues in Closely related Eutherian. Kidney Intl 67:1731-8 (2005)
- eng YH, Wang L, Wang Q, Li X, Zeng R, Gorodeski GI. ATP ligation stimulates GRK-3 - mediated phosphorylation and -arrestin-2- and dynamin-dependent internalization of the P2X7-receptor. Am J Physiol Cell Physiol. 288:C1342-56 (2005)
- Feng YH, Zhou L, Qiu R, and Robin Zeng. Single mutations at Asn295 and Leu305 in the cytoplasmic half of TM7 of the AT1 receptor induce promiscuous agonist specificity for angiotensin II fragments - A PSEUDO-CONSTITUTIVE ACTIVITY. Mol Pharmacol 68:347-55 (2005)
- Feng YH, Ding Y, Ren S, Xu C, Karnik SS. Unconventional homologous internalization of the AT1 receptor induced by G protein-independent signals. Hypertension 46:419-25 (2005)
- Feng YH, Li X, Wang L, Zhou L, Gorodeski GI. A truncated P2X7 receptor variant (P2X7-j) endogenously expressed in cervical cancer cells antagonizes the full-length P2X7 receptor through hetero-oligomerization. J Biol Chem. 281:17228-37 (2006)
Irwin Lucki, Ph.D.
Name: Irwin Lucki, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Professor and Chair
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Neuropharmacology
Antidepressant drugs
Email:
Office Phone:
(301) 295-3248
Education
Education: 1972 B.A. University of Illinois, Psychology
1976 M.A. University of Iowa, Psychology
1979 Ph.D. University of Iowa, Biopsychology
Postgraduate Training:
1979-1981 Postdoctoral Research Fellow, Psychopharmacology Training Program, Department of Psychiatry, University of Pennsylvania
1976 M.A. University of Iowa, Psychology
1979 Ph.D. University of Iowa, Biopsychology
Postgraduate Training:
1979-1981 Postdoctoral Research Fellow, Psychopharmacology Training Program, Department of Psychiatry, University of Pennsylvania
Biography
Selected from 180 publications:
Cryan, J.F., Valentino, R.J. and Lucki, I. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neuroscience and Biobehavioral Reviews, 2005, 29:547-569.
Valentino, R.J., Lucki, I. and Van Bockstaele, E. Corticotropin-releasing factor in the dorsal raphe nucleus: Linking stress coping and addiction. Brain Research, 2010, 1314:29-37. PMC2819581
Ho, N., Sommers, M.S. and Lucki, I. Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression. Neuroscience and Biobehavioral Reviews, 2013, 37:1346-1362. PMC3788092
Browne, C.A. and Lucki, I. Mechanisms mediating the antidepressant-like Lucki, I. The spectrum of behaviors influenced by serotonin. Biological Psychiatry, 1998, 44:151-162.
Page, M.E., Cryan, J.F., Sullivan, A., Dalvi, A. and Lucki, I. Behavioral and neurochemical effects of EMD 68843: A combined selective inhibitor of serotonin reuptake and partial 5-HT1A receptor agonist. Journal of Pharmacology and Experimental Therapeutics, 2002, 302:1-8.
Carr, G.V. and Lucki, I. The role of serotonin receptor subtypes in treating depression: A review of animal studies. Psychopharmacology, 2011, 213:265-287. PMC3374933
Carr, G.V., Schechter, L.E. and Lucki, I. Antidepressant and anxiolytic effects of
selective 5-HT6 receptor agonists in rats. Psychopharmacology, 2011, 213:499-507. PMC2910165
effects of ketamine: Screening for fast-acting novel antidepressants. Frontiers in Neuropharmacology, 2013, 4:161, 1-18. PMC3873522.
Mayorga, A.J., Dalvi, A., Page, M.E., Zimov-Levinson, S., Hen R. and Lucki, I. Antidepressant-like behavioral effects in 5-HT1A and 5-HT1B receptor mutant mice. Journal of Pharmacology and Experimental Therapeutics, 2001, 298:1101-1107.
Cryan, J.F., O’Leary, O.F., Jin, S.-H., Friedland, J.C., Ouyang, M., Hirsch, B.R., Page, M.E., Dalvi, A., Thomas, S.A. and Lucki, I. Norepinephrine deficient mice lack responses to antidepressant drugs, including SSRIs. Proceedings of the National Academy of Sciences, 2004, 101:8186-8191.
O’Leary, O.F., Bechtholt, A.J., Crowley, J.J., Valentino, R.J. and Lucki, I. The role of noradrenergic tone in the dorsal raphe nucleus of the mouse in the acute behavioral effects of antidepressant drugs. European Neuropsychopharmacology, 2007, 17:215-226.
Balu, D.T., Turner, J.R., Brookshire, B.R., Hill, T.E., Blendy, J.A. and Lucki, I. Brain monoamines and responses to antidepressant drugs in MRL/MpJ versus C57BL/6J and mice. Neuropharmacology, 2013, 67:503-510. PMC437180
Cryan, J.F., Markou, A. and Lucki, I. Assessing antidepressant-like activity in laboratory animals: Recent developments and future needs. Trends in Pharmacological Sciences, 2002, 23(5): 238-245.
Crowley, J.J. and Lucki, I. Opportunities to discover genes regulating depression and antidepressant response from rodent behavioral genetics. Current Pharmaceutical Design, 11:157-169, 2005.
Bechtholt, A.J., Valentino, R.J. and Lucki, I. Overlapping and distinct brain regions associated
with the anxiolytic effects of chlordiazepoxide and chronic fluoxetine. Neuropsychopharmacology, 2008, 33:2117-2130.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Price, M. L., Curtis, A.L., Kirby, L.G., Valentino, R.J. and Lucki, I. Biphasic effects of corticotropin-releasing factor on brain serotonergic activity. Neuropsychopharmacology, 1998, 18:492-502.
Price, M.L. and Lucki, I. Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor. Journal of Neuroscience, 2001, 21:2833-2841.
Howard, O., Carr, G.V., Hill, T.E., Valentino, R.J. and Lucki, I. Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin. Psychopharmacology, 2008, 199:569-82. PMC2744742
Snyder, K.P., Hill-Smith, T.E., Lucki, I. and Valentino, R.J. Corticotropin-releasing factor in the rat dorsal raphe nucleus promotes different forms of behavioral flexibility depending on social stress history. Neuropsychopharmacology, 2015, 40:2517-25. PMCID in process.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Falcon, E., Maier, K., Robinson, S.A. and Lucki, I. Effects of buprenorphine on behavioral tests for antidepressant and anxiolytic drugs in mice. Psychopharmacology, 2015, 232:907-915. PMC4326609
Browne, C.A., van Nest, D. and Lucki, I. Antidepressant-like effects of buprenorphine in rats are strain dependent. Behavioural Brain Research, 2015, 278:385-392. PMC4382376
Falcon, E., Browne, C.A., Leon, R.M., Fleites, V.C., Sweeney, R., Kirby, L.G. and Lucki, I. Antidepressant-like effects of buprenorphine are mediated by kappa opioid receptors. Neuropsychopharmacology, 2016, 41(9):2344-2351. PMC4946065
A full bibliography of over 170 peer-reviewed publications is available at: http://www.ncbi.nlm.nih.gov/sites/myncbi/irwin.lucki.1/bibliography/45296221/public/?sort=date&direction=ascending.
Cryan, J.F., Valentino, R.J. and Lucki, I. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neuroscience and Biobehavioral Reviews, 2005, 29:547-569.
Valentino, R.J., Lucki, I. and Van Bockstaele, E. Corticotropin-releasing factor in the dorsal raphe nucleus: Linking stress coping and addiction. Brain Research, 2010, 1314:29-37. PMC2819581
Ho, N., Sommers, M.S. and Lucki, I. Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression. Neuroscience and Biobehavioral Reviews, 2013, 37:1346-1362. PMC3788092
Browne, C.A. and Lucki, I. Mechanisms mediating the antidepressant-like Lucki, I. The spectrum of behaviors influenced by serotonin. Biological Psychiatry, 1998, 44:151-162.
Page, M.E., Cryan, J.F., Sullivan, A., Dalvi, A. and Lucki, I. Behavioral and neurochemical effects of EMD 68843: A combined selective inhibitor of serotonin reuptake and partial 5-HT1A receptor agonist. Journal of Pharmacology and Experimental Therapeutics, 2002, 302:1-8.
Carr, G.V. and Lucki, I. The role of serotonin receptor subtypes in treating depression: A review of animal studies. Psychopharmacology, 2011, 213:265-287. PMC3374933
Carr, G.V., Schechter, L.E. and Lucki, I. Antidepressant and anxiolytic effects of
selective 5-HT6 receptor agonists in rats. Psychopharmacology, 2011, 213:499-507. PMC2910165
effects of ketamine: Screening for fast-acting novel antidepressants. Frontiers in Neuropharmacology, 2013, 4:161, 1-18. PMC3873522.
Mayorga, A.J., Dalvi, A., Page, M.E., Zimov-Levinson, S., Hen R. and Lucki, I. Antidepressant-like behavioral effects in 5-HT1A and 5-HT1B receptor mutant mice. Journal of Pharmacology and Experimental Therapeutics, 2001, 298:1101-1107.
Cryan, J.F., O’Leary, O.F., Jin, S.-H., Friedland, J.C., Ouyang, M., Hirsch, B.R., Page, M.E., Dalvi, A., Thomas, S.A. and Lucki, I. Norepinephrine deficient mice lack responses to antidepressant drugs, including SSRIs. Proceedings of the National Academy of Sciences, 2004, 101:8186-8191.
O’Leary, O.F., Bechtholt, A.J., Crowley, J.J., Valentino, R.J. and Lucki, I. The role of noradrenergic tone in the dorsal raphe nucleus of the mouse in the acute behavioral effects of antidepressant drugs. European Neuropsychopharmacology, 2007, 17:215-226.
Balu, D.T., Turner, J.R., Brookshire, B.R., Hill, T.E., Blendy, J.A. and Lucki, I. Brain monoamines and responses to antidepressant drugs in MRL/MpJ versus C57BL/6J and mice. Neuropharmacology, 2013, 67:503-510. PMC437180
Cryan, J.F., Markou, A. and Lucki, I. Assessing antidepressant-like activity in laboratory animals: Recent developments and future needs. Trends in Pharmacological Sciences, 2002, 23(5): 238-245.
Crowley, J.J. and Lucki, I. Opportunities to discover genes regulating depression and antidepressant response from rodent behavioral genetics. Current Pharmaceutical Design, 11:157-169, 2005.
Bechtholt, A.J., Valentino, R.J. and Lucki, I. Overlapping and distinct brain regions associated
with the anxiolytic effects of chlordiazepoxide and chronic fluoxetine. Neuropsychopharmacology, 2008, 33:2117-2130.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Price, M. L., Curtis, A.L., Kirby, L.G., Valentino, R.J. and Lucki, I. Biphasic effects of corticotropin-releasing factor on brain serotonergic activity. Neuropsychopharmacology, 1998, 18:492-502.
Price, M.L. and Lucki, I. Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor. Journal of Neuroscience, 2001, 21:2833-2841.
Howard, O., Carr, G.V., Hill, T.E., Valentino, R.J. and Lucki, I. Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin. Psychopharmacology, 2008, 199:569-82. PMC2744742
Snyder, K.P., Hill-Smith, T.E., Lucki, I. and Valentino, R.J. Corticotropin-releasing factor in the rat dorsal raphe nucleus promotes different forms of behavioral flexibility depending on social stress history. Neuropsychopharmacology, 2015, 40:2517-25. PMCID in process.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Falcon, E., Maier, K., Robinson, S.A. and Lucki, I. Effects of buprenorphine on behavioral tests for antidepressant and anxiolytic drugs in mice. Psychopharmacology, 2015, 232:907-915. PMC4326609
Browne, C.A., van Nest, D. and Lucki, I. Antidepressant-like effects of buprenorphine in rats are strain dependent. Behavioural Brain Research, 2015, 278:385-392. PMC4382376
Falcon, E., Browne, C.A., Leon, R.M., Fleites, V.C., Sweeney, R., Kirby, L.G. and Lucki, I. Antidepressant-like effects of buprenorphine are mediated by kappa opioid receptors. Neuropsychopharmacology, 2016, 41(9):2344-2351. PMC4946065
A full bibliography of over 170 peer-reviewed publications is available at: http://www.ncbi.nlm.nih.gov/sites/myncbi/irwin.lucki.1/bibliography/45296221/public/?sort=date&direction=ascending.
Representative publications, projects, and/or deployments
- 2007 - present, Principal Field Editor, Psychopharmacology
- 1995 - present, Editorial Advisory Board, Neuropsychopharmacology
- 2014 – present, Editorial Advisory Board, Neurobiology of Stress
- Buprenorphine for Depression and Anxiety.PI. NIMH, R01 MH92412, 2012-2018. Total direct costs = $1,250,000. The goal of this grant is to examine animal models supporting the development of buprenorphine for the clinical treatment of depression and anxiety.
- Kappa Receptor Antagonists as Rapid Acting Antidepressants. PI. NIMH, R01 MH105623, 2016-2020. Total direct costs = $1,000,000. The goal of this grant is to study animal models supporting the development of novel kappa receptor antagonists for the clinical treatment of mood disorders.
- Training Program in Neuropsychopharmacology. NIMH, T32 MH14654-34-38, 1978-2021. I was Training Program Director at the University of Pennsylvania 1992-2016.
- Regulation of Hippocampal Neurogenesis by Antidepressants. PI. NIMH, R01 MH86599, 2009-2015.
- Biology of Serotonin in Brain; Program Project Grant: Irwin Lucki, Ph.D., Program Director (1994-2007). NIMH, PO1-MH-48125.
- Regulation of Neurogenesis by Stress and Antidepressants. Program Director. National Cooperative Drug Discovery Group involving University of Pennsylvania and Wyeth Neuroscience. U01-MH 72832, 2005-2009.
Bibliography
- 2016- present Professor (with tenure) and Chair, Department of Pharmacology and Molecular Therapeutics, Uniformed University of the Health Sciences, Bethesda MD
- 2016-present Professor, Department of Psychiatry, Uniformed University of the Health Sciences, Bethesda MD
- 1996-2016 Professor of Psychology in Psychiatry (with tenure), Depts. of Psychiatry and Pharmacology, University of Pennsylvania, Philadelphia PA
- 1990-1996 Associate Professor of Psychology in Psychiatry (with tenure), Depts. of Psychiatry and Pharmacology, University of Pennsylvania, Philadelphia PA
- 1989-1990 Assistant Professor, Department of Pharmacology, University of Pennsylvania, Philadelphia PA
- 1984-1990 Assistant Professor of Psychology in Psychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia PA
- 1981-1984 Research Associate, Department of Psychiatry, University of Pennsylvania, Philadelphia PA
Aviva J Symes, Ph.D.
Name: Aviva J Symes, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Traumatic brain injury
Role of renin angiotensin system in the brain after injury
Email:
Office Phone:
(301) 295-3234
Education
B.Sc.(Hons). Biochemistry, University of Manchester, UK
Ph.D. Biochemistry/Molecular Biology, University College London, UK
Post-doctoral training: Massachusetts General Hospital/ Harvard Medical School, Boston.
Ph.D. Biochemistry/Molecular Biology, University College London, UK
Post-doctoral training: Massachusetts General Hospital/ Harvard Medical School, Boston.
Biography
RESEARCH INTERESTS:
My lab aims to understand the mechanisms through which the brain responds to traumatic injury and more specifically to delineate the pathways through which detrimental neuroinflammatory cascades can be altered to enhance recovery after injury. The initial lesion can produce significant tissue damage and breakdown of the blood brain barrier. These immediate effects lead to activation of many secondary cascades involving interplay between endogenous surviving neurons and glia, and infiltrating cells and molecules from the bloodstream. Injury therefore leads to acute neuroinflammatory cascades, and also to more chronic inflammatory effects. Indeed, activated microglia have been documented in postmortem brains many years after the initial insult. Our lab focuses on understanding the molecular signaling cascades that occur after injury in addition to testing potential therapeutics to enhance recovery from injury. We currently utilize several different rodent models of traumatic brain injury (TBI), with assays ranging from behavioral through molecular to understand the complex interactions that occur after injury, and to determine how manipulations may impact on functional recovery. We also utilize primary cell cultures to tease apart the molecular signaling pathways that contribute to inflammation after injury.
Angiotensin receptor blockers as potential therapeutics for TBI
Angiotensin receptor blockers (ARBs) are widely used FDA-approved anti-hypertension drugs with a favorable side effect profile that have been used as a mechanism for reducing the amount of TGF-β signaling in several different organ systems. In the CNS, ARBs have also been shown to be neuroprotective, anti-inflammatory and protective of the cerebral blood flow (CBF). The brain possesses its own renin angiotensin system, with many different components of the system expressed in the different cell types in the brain. However, in addition to acting as antagonists at the Angiotensin II receptor 1 (AT1R) some ARBs also possess potent PPARγ agonist activity that enhances their anti-inflammatory action. We have demonstrated that the ARB candesartan, lessens inflammation, reduces lesion volume, limits glial reactivity, increases neuronal survival and improves motor and cognitive recovery up to 28 days after injury. These beneficial effects are seen when low-dose candesartan is administered up to 6 hours after injury, a clinically acceptable therapeutic window. Our data suggest that both AT1 receptor antagonism and PPARγ agonism contribute to the efficacy of ARB treatment after TBI and it is this multimodal action by a single drug that makes it a strong candidate for TBI clinical trials. We are pursuing translational studies for candesartan for brain injury in addition to investigating the consequences of TBI on the endogenous renin-angiotensin system in the brain.
TGF-β signaling after injury
TGF-β is an injury induced cytokine that has complex roles in the central nervous system. After brain injury TGF-β can promote astrogliosis and enhance the deposition of molecules inhibitory to regeneration in the glial scar. Yet TGF-β is also neuroprotective indicating the sometimes conflicting roles of this cytokine. We have shown that after a penetrating brain injury mice that lack expression of the TGF-β signaling molecule Smad3, form a glial scar more quickly, with a smaller scar, than wild type mice. However, we also found that Smad3 null mice have more pronounced neuronal loss after injury. Thus, global interference with TGF-β signaling is not a desirable therapeutic option. Further, TGF-β is anti-inflammatory in some contexts – so chronic repression of TGF-β signaling pathways may enhance inflammation. In primary microglial cultures we have shown that inflammatory pathways downregulate TGF-β receptor expression, allowing for prolonged enhancement of the inflammatory activated state.
My lab aims to understand the mechanisms through which the brain responds to traumatic injury and more specifically to delineate the pathways through which detrimental neuroinflammatory cascades can be altered to enhance recovery after injury. The initial lesion can produce significant tissue damage and breakdown of the blood brain barrier. These immediate effects lead to activation of many secondary cascades involving interplay between endogenous surviving neurons and glia, and infiltrating cells and molecules from the bloodstream. Injury therefore leads to acute neuroinflammatory cascades, and also to more chronic inflammatory effects. Indeed, activated microglia have been documented in postmortem brains many years after the initial insult. Our lab focuses on understanding the molecular signaling cascades that occur after injury in addition to testing potential therapeutics to enhance recovery from injury. We currently utilize several different rodent models of traumatic brain injury (TBI), with assays ranging from behavioral through molecular to understand the complex interactions that occur after injury, and to determine how manipulations may impact on functional recovery. We also utilize primary cell cultures to tease apart the molecular signaling pathways that contribute to inflammation after injury.
Angiotensin receptor blockers as potential therapeutics for TBI
Angiotensin receptor blockers (ARBs) are widely used FDA-approved anti-hypertension drugs with a favorable side effect profile that have been used as a mechanism for reducing the amount of TGF-β signaling in several different organ systems. In the CNS, ARBs have also been shown to be neuroprotective, anti-inflammatory and protective of the cerebral blood flow (CBF). The brain possesses its own renin angiotensin system, with many different components of the system expressed in the different cell types in the brain. However, in addition to acting as antagonists at the Angiotensin II receptor 1 (AT1R) some ARBs also possess potent PPARγ agonist activity that enhances their anti-inflammatory action. We have demonstrated that the ARB candesartan, lessens inflammation, reduces lesion volume, limits glial reactivity, increases neuronal survival and improves motor and cognitive recovery up to 28 days after injury. These beneficial effects are seen when low-dose candesartan is administered up to 6 hours after injury, a clinically acceptable therapeutic window. Our data suggest that both AT1 receptor antagonism and PPARγ agonism contribute to the efficacy of ARB treatment after TBI and it is this multimodal action by a single drug that makes it a strong candidate for TBI clinical trials. We are pursuing translational studies for candesartan for brain injury in addition to investigating the consequences of TBI on the endogenous renin-angiotensin system in the brain.
TGF-β signaling after injury
TGF-β is an injury induced cytokine that has complex roles in the central nervous system. After brain injury TGF-β can promote astrogliosis and enhance the deposition of molecules inhibitory to regeneration in the glial scar. Yet TGF-β is also neuroprotective indicating the sometimes conflicting roles of this cytokine. We have shown that after a penetrating brain injury mice that lack expression of the TGF-β signaling molecule Smad3, form a glial scar more quickly, with a smaller scar, than wild type mice. However, we also found that Smad3 null mice have more pronounced neuronal loss after injury. Thus, global interference with TGF-β signaling is not a desirable therapeutic option. Further, TGF-β is anti-inflammatory in some contexts – so chronic repression of TGF-β signaling pathways may enhance inflammation. In primary microglial cultures we have shown that inflammatory pathways downregulate TGF-β receptor expression, allowing for prolonged enhancement of the inflammatory activated state.
Bibliography
Biosketch Link:
- Bone morphogenetic protein-2-mediated pain and inflammation in a rat model of posterolateral arthrodesis. Mitchell K, Shah JP, Dalgard CL, Tsytsikova LV, Tipton AC, Dmitriev AE, Symes AJ. BMC neuroscience. 2016; 17(1):80. PubMed [journal]PMID: 27905881 PMCID: PMC5134101
- Neurorestoration after traumatic brain injury through angiotensin II receptor blockage. Villapol S, Balarezo MG, Affram K, Saavedra JM, Symes AJ. Brain : a journal of neurology. 2015; 138(Pt 11):3299-315. PubMed [journal]PMID: 26115674 PMCID: PMC4731413
- Runx1 promotes proliferation and neuronal differentiation in adult mouse neurosphere cultures. Logan TT, Rusnak M, Symes AJ. Stem cell research. 2015; 15(3):554-564. PubMed [journal]PMID: 26473321
- Hepatic expression of serum amyloid A1 is induced by traumatic brain injury and modulated by telmisartan. Villapol S, Kryndushkin D, Balarezo MG, Campbell AM, Saavedra JM, Shewmaker FP, Symes AJ. The American journal of pathology. 2015; 185(10):2641-52. PubMed [journal]PMID: 26435412 PMCID: PMC4607758
- . Temporal patterns of cortical proliferation of glial cell populations after traumatic brain injury in mice. Susarla BT, Villapol S, Yi JH, Geller HM, Symes AJ. ASN neuro. 2014; 6(3):159-70. PubMed [journal]PMID: 24670035 PMCID: PMC4013687
- LPS antagonism of TGF-β signaling results in prolonged survival and activation of rat primary microglia. Mitchell K, Shah JP, Tsytsikova LV, Campbell AM, Affram K, Symes AJ. Journal of neurochemistry. 2014; 129(1):155-68. PubMed [journal]PMID: 24251648
- Temporal dynamics of cerebral blood flow, cortical damage, apoptosis, astrocyte-vasculature interaction and astrogliosis in the pericontusional region after traumatic brain injury. Villapol S, Byrnes KR, Symes AJ. Frontiers in neurology. 2014; 5:82. PubMed [journal]PMID: 24926283 PMCID: PMC4044679
- Smad3 deficiency increases cortical and hippocampal neuronal loss following traumatic brain injury. Villapol S, Wang Y, Adams M, Symes AJ. Experimental neurology. 2013; 250:353-65. PubMed [journal]PMID: 24120438
- TGF-β superfamily gene expression and induction of the Runx1 transcription factor in adult neurogenic regions after brain injury. Logan TT, Villapol S, Symes AJ. PloS one. 2013; 8(3):e59250. PubMed [journal]PMID: 23555640 PMCID: PMC3605457
- Candesartan, an angiotensin II AT₁-receptor blocker and PPAR-γ agonist, reduces lesion volume and improves motor and memory function after traumatic brain injury in mice. Villapol S, Yaszemski AK, Logan TT, Sánchez-Lemus E, Saavedra JM, Symes AJ. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2012; 37(13):2817-29. PubMed [journal]PMID: 22892395 PMCID: PMC3499714
PHA - Cellular & Molecular Pharmacology
Regina M Day, Ph.D.
Name: Regina M Day, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Vice Chair
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Email:
Office Phone:
(301) 295-3236
Education
A.B. Smith College, Northampton, MA, USA
Ph.D. Tufts University, Boston, MA, USA
Ph.D. Tufts University, Boston, MA, USA
Biography
Introduction and overview:
My laboratory is dedicated to understanding normal tissue repair processes and how the repair process is altered in fibrotic remodeling. Normal tissue regeneration for wound healing is a critical focus of research for the military as well as for the medical field in general. The long term goal of my laboratory is to understand the mechanism of fibrotic repair and to identify therapeutic agents to prevent and/or treat this disease. The lung provides an excellent model system for investigation, since it is uniquely sensitive to chemicals and radiation that produce well-defined stages of injury, inflammation, attempted repair, and repair failure/remodeling. Lung fibrosis is a progressive disease with no treatments and poor prognosis. Our laboratory uses in vivo animal models and in vitro primary cell cultures to systematically elucidate the mechanisms of tissue regeneration and fibrotic remodeling at the molecular, biochemical, cellular, and tissue levels.
Radiation countermeasures for the lung and hematopoietic systems and radiation biology:
• Radiation countermeasures for both the hematopoietic and lung tissues. Radiation-induced lung injury is a late effect of radiation, whereas hematopoietic injuries are an acute radiation injury. Because of the Department of Defense’s interest in protection against both acute and delayed injuries, we were requested to develop a murine model for both the hematopoietic and pulmonary injuries, and to test radiation countermeasures in both systems. My laboratory developed an animal model system incorporating both hematopoietic and lung radiation injuries. We have determined the mechanism of action of captopril protection in both tissues, as a part of the requirement for radiation countermeasure development under the Animal Rule for the FDA. We are currently expanding our testing of captopril in the minipig model of radiation acute injuries.
• My laboratory developed a cell culture system for studying the molecular mechanisms of radiation-induced senescence in normal (non-transformed, non-immortalized) cells. Our research demonstrated for the first time that normal lung and skin cells primarily undergo accelerated senescence, and not apoptosis, in response to radiation. We identified an early cellular response to radiation is the induction of insulin-like growth factor 1 (IGF-1) and the activation of its receptor (IGF-1R). These novel and provocative observations prompted us to hypothesize that senescence is the precipitating state for radiation pathology.
Hepatocyte growth factor (HGF) signaling for tissue repair and suppression of fibrosis:
• My laboratory has identified novel signaling pathways for HGF-induced normal tissue repair mechanisms. HGF expression is required for normal tissue repair, and HGF can redirect repair away from fibrotic remodeling to induce normal tissue regrowth. To understand how HGF can accomplish this, my research team investigated signal transduction mechanisms for HGF suppression of apoptosis in epithelial and endothelial cells that is induced during fibrosis. We next investigated the mechanisms by which HGF expression is suppressed during fibrotic remodeling. We recently uncovered a novel mechanism by which miRNA regulates HGF mRNA half-life under fibrotic conditions. This research led to the identification of potential novel anti-fibrotic treatment strategies.
• My laboratory developed a synthetic peptide based on other proteins that bind the HGF receptor, MET. The structural complexity of the full length HGF structure has prevented its development as a pharmaceutical agent, and full length HGF has not been successfully produced in sufficient quantities for clinical use. A patent was submitted by the USU/HJF JOTT based on these findings. Our laboratory currently aims to improve the design of this protein, to improve stability and increase receptor affinity.
My laboratory is dedicated to understanding normal tissue repair processes and how the repair process is altered in fibrotic remodeling. Normal tissue regeneration for wound healing is a critical focus of research for the military as well as for the medical field in general. The long term goal of my laboratory is to understand the mechanism of fibrotic repair and to identify therapeutic agents to prevent and/or treat this disease. The lung provides an excellent model system for investigation, since it is uniquely sensitive to chemicals and radiation that produce well-defined stages of injury, inflammation, attempted repair, and repair failure/remodeling. Lung fibrosis is a progressive disease with no treatments and poor prognosis. Our laboratory uses in vivo animal models and in vitro primary cell cultures to systematically elucidate the mechanisms of tissue regeneration and fibrotic remodeling at the molecular, biochemical, cellular, and tissue levels.
Radiation countermeasures for the lung and hematopoietic systems and radiation biology:
• Radiation countermeasures for both the hematopoietic and lung tissues. Radiation-induced lung injury is a late effect of radiation, whereas hematopoietic injuries are an acute radiation injury. Because of the Department of Defense’s interest in protection against both acute and delayed injuries, we were requested to develop a murine model for both the hematopoietic and pulmonary injuries, and to test radiation countermeasures in both systems. My laboratory developed an animal model system incorporating both hematopoietic and lung radiation injuries. We have determined the mechanism of action of captopril protection in both tissues, as a part of the requirement for radiation countermeasure development under the Animal Rule for the FDA. We are currently expanding our testing of captopril in the minipig model of radiation acute injuries.
• My laboratory developed a cell culture system for studying the molecular mechanisms of radiation-induced senescence in normal (non-transformed, non-immortalized) cells. Our research demonstrated for the first time that normal lung and skin cells primarily undergo accelerated senescence, and not apoptosis, in response to radiation. We identified an early cellular response to radiation is the induction of insulin-like growth factor 1 (IGF-1) and the activation of its receptor (IGF-1R). These novel and provocative observations prompted us to hypothesize that senescence is the precipitating state for radiation pathology.
Hepatocyte growth factor (HGF) signaling for tissue repair and suppression of fibrosis:
• My laboratory has identified novel signaling pathways for HGF-induced normal tissue repair mechanisms. HGF expression is required for normal tissue repair, and HGF can redirect repair away from fibrotic remodeling to induce normal tissue regrowth. To understand how HGF can accomplish this, my research team investigated signal transduction mechanisms for HGF suppression of apoptosis in epithelial and endothelial cells that is induced during fibrosis. We next investigated the mechanisms by which HGF expression is suppressed during fibrotic remodeling. We recently uncovered a novel mechanism by which miRNA regulates HGF mRNA half-life under fibrotic conditions. This research led to the identification of potential novel anti-fibrotic treatment strategies.
• My laboratory developed a synthetic peptide based on other proteins that bind the HGF receptor, MET. The structural complexity of the full length HGF structure has prevented its development as a pharmaceutical agent, and full length HGF has not been successfully produced in sufficient quantities for clinical use. A patent was submitted by the USU/HJF JOTT based on these findings. Our laboratory currently aims to improve the design of this protein, to improve stability and increase receptor affinity.
Representative publications, projects, and/or deployments
- 12/2016 – present Vice Chair USUHS School of Medicine Department of Pharmacology and Molecular Therapeutics
- 7/2014- present Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 11/2014 Adjunct Professor Georgetown University School of Medicine Pulmonary, Critical Care, and Sleep Medicine
- 2/2010- 7/2014 Associate Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 7/2004-1/2010 Tenure Track Assistant Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 1/2004-6/2004 Research Assistant Professor Georgetown Univ. School of Medicine Pulmonary, Critical Care, and Sleep Medicine
- 8/1999-12/2004 Research Assistant Professor Tufts-New England Medical Ctr Pulmonary, Critical Care, and Sleep Medicine Div
- Postdoctoral Fellow NIH, NCI, Lab of Cellular, Molecular Biology
Bibliography
- Landauer, M.R., Harvey, A.J., Kaytor, M.D., Day, R.M. (2019) Mechanism and therapeutic window of a genistein nanosuspension to protect against hematopoietic-acute radiation syndrome. J. Radiat. Res. In press.
- McCart, E.A., Lee, Y.H., Jha, J., Mungunsukh, O., Rittase, W.B., Summers, T.A., Muir, J., Day R.M. (2019) Delayed captopril administration mitigates hematopoietic injury in a murine model of total body irradiation. Sci Reports, 9: 2198.
- Bylicky, M.A., Mueller, G.P., Day, R.M. (2019) Radiation resistance of normal human astrocytes: role of non-homologous end joining DNA repair activity. J Radiat Res. 60: 37-50.
- Corey, S.J., Jha, J., McCart, E.A., Rittase, W.B., George, J., Mattapallil, J.J., Mehta, H., Ognoon, M., Bylicky, M.A., Summers, T.A., Day, R.M. (2018) Captopril mitigates splenomegaly and myelofibrosis in the Gata1low murine model of myelofibrosis. J Cell Mol Med, 22: 4274-4282.
- Du, Y., Banas, R.A., McCart, E.A., George, J., Oakley, K., Han, Y., Landauer, M.R., Day, R.M. (2018) Effect of human amnion-derived multipotent progenitor cells on hematopoietic recovery after total body irradiation in C57BL/6 mice. Int J Radiat Res, 16:155-168.
- Zhao*, J., Day*, R.M., Jin, J-Y., Quint, L., Williams, H., Ferguson, C., Yan, L., King, M., Albsheer, A., Matuszak, M., Kong, S-M. (2017) Thoracic radiation-induced pleural effusion and risk factors in patients with lung cancer. Oncotarget, 8: 97623-32.
- McCart, E.A., Lombardini, E., Mog, S.R., Panganiban, R.A.M., Dickson, K.M., Mansur, R.A., Nagy, V., Kim, S-Y., Selwyn, R., Landauer, M.R., Darling, T.N., Day, R.M. (2017) Accelerated senescence in a murine model of radiation-induced skin injury. J Radiat Res, 58: 636-646.
- Brzezniak, C., Oronsky, B., Trepel, J., Summers, T.A. Jr., Cabrales, P., Lee, M.J., Day, R., Jha, S., Caroen, S, Zeman, K, Ferr,y L, Harmer, C, Oronsky, N, Lybeck, M, Lybeck, HE, Brown, JF, Reid, T.R., Carter, C.A. RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor. Case Rep Oncol. 2017;10:276-280.
- Mungunsukh, O., Lee, Y.H., Bottaro, D.P., Day, R.M. (2016) The hepatocyte growth factor isoform NK2 activates motogenesis and survival but not proliferation due to lack of Akt activation. Cell Signal, 28, 1114-23.
- Barshishat-Kupper, M., McCart E.A., Freedy, J.G., Tipton A.J., Nagy V., Kim, S.-Y., Landauer, M.R., Mueller G.P., Day R.M. (2015) Protein oxidation in the lungs of C57BL/6J mice following X-irradiation. Proteomes, 3, 249-265.
Ying-Hong Feng, M.D., Ph.D
Name: Ying-Hong Feng, M.D., Ph.D
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Dr.
Faculty Rank:
Associate Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Receptor structure-function & signaling; Epigenome editing & transcription regulation
Translational research in neurodegenerative diseases, mood disorder, cancer, diabetes, and cardiovascular diseases
Email:
Office Phone:
(301) 295-3232
Department Website:
Education
1978-1983, M.D., Wuhan University School of Medicine, Wuhan, China
1990-1994, Ph.D., Biochemistry, University of Oxford, Oxford, UK
1994-1997, Postdoctoral, Molecular Cardiology, Cleveland Clinic Foundation
1990-1994, Ph.D., Biochemistry, University of Oxford, Oxford, UK
1994-1997, Postdoctoral, Molecular Cardiology, Cleveland Clinic Foundation
Biography
Feng’s lab has three research programs. The first is about crosstalk signaling of receptors in the form of receptor dimerization in pathophysiology such as vascular inflammation, metabolism (type 2 diabetes), pain (silent myocardial ischemia), depression, immunosuppression, cancer progression, and etc. The second is about translational research on neurodegenerative diseases and cancer with focus on novel splicing variants, of critical genes that are known to play an important role in depression, neurodegeneration, neuroregeneration, exosome biology, tumorigenesis, and cancer progression. The last is to develop novel technologies for genome editing and epigenome editing.
Representative publications, projects, and/or deployments
- Feng YH, Li X, Zeng R, Gorodeski GI. Endogenously Expressed Truncated P2X7 Receptor Lacking the C-Terminus is Preferentially Upregulated in Epithelial Cancer Cells and Fails to Mediate Ligand-Induced Pore Formation and Apoptosis. Nucleosides Nucleotides Nucleic Acids. 25:1271-6 (2006)
- Feng YH, Li X, Zeng R, Gorodeski GI. Endogenously expressed truncated P2X7 receptor lacking the C-terminus is preferentially upregulated in epithelial cancer cells and fails to mediate ligand-induced pore formation and apoptosis. Nucleosides Nucleotides Nucleic Acids. 25(9-11):1271-6 (2006)
- Chen M, Wang T, Liao ZX, Pan XL, Feng YH, Wang H. Nicotine-induced prenatal overexposure to maternal glucocorticoid and intrauterine growth retardation in rat. Exp Toxicol Pathol. 59: 245-51 (2007)
- 30. Zhang X, Wang G, Dupre DJ, Feng Y, Robitaille M, Lazartigues E, Feng YH, Hebert TE, Wu G. Rab1 GTPase and dimerization in the cell surface expression of angiotensin II type 2 receptor. J Pharmacol Exp Ther. 330(1):109-17 (2009)
- 31. Guo J, Li ZC and Feng YH. Expression and activation of the reprogramming transcription factors. Biochem Biophys Res Commun. 390(4):1081-6 (2009)
- 32. Zhang J, Villacorta L, Chang L, Fan Z, Hamblin M, Zhu T, Chen CS, Cole MP, Schopfer FJ, Deng CX, Garcia-Barrio MT, Feng YH, Freeman BA, Chen YE. Nitrated oleic acid inhibits Angiotensin II-induced hypertension. Circ Res, 107(4):540-8 (2010)
- 34. Day RD, Lee YH, Han L, Kim YC, Feng YH. Angiotensin II activates AMPK for execution of apoptosis through energy-dependent and -independent mechanisms. Am J Physiol Lung Cell Mol Physiol, 301(5):L772-81 (2011)
- 35. Wang TT, Chen M, Liu L, Cheng H, Yan YE, Feng YH*, Wang H. Nicotine induces a single CpG methylation in the StAR promoter: a potential mechanism for reduced StAR expression and cortisol production. Toxicol and Applied Pharmacol. 257(3):328-37 (2011) *Co-senior author
- 37. Wang H, Yin H, Yan F, Sun M, Du L, Peng W, Li Q, Feng Y, Zhou Y. Folate-mediated mitochondrial targeting with doxorubicin-polyrotaxane nanoparticles overcomes multidrug resistance. Oncotarget. 6(5):2827-42 (2015).
- 38. Li K, Pang J, Cheng H, Wei-Peng Liu WP, Chen MK, Yun Luo Y, Di JM, Zhang H, Huang WT, Li LY, Shao CK, Feng YH*, Gao X. Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase. Oncotarget. 6(12):10030-44 (2015) *Co-senior author
Bibliography
- Feng YH, Saad Y and Karnik SS. Reversible Inactivation of AT2 Angiotensin II Receptor from Cysteine-Disulfide Bond Exchange. FEBS Letters 484, 133-138 (2000)
- Feng YH, Sun Y, and Douglas JG. G??-Independent Constitutive Association of Gs? with SHP-1 and Angiotensin II Receptor AT2 Is Essential in AT2-mediated Activation of SHP-1. Proc. Natl. Acad. Sci. USA 99:12049-12054 (2002)
- Wang Q, Li X, Wang L, Feng YH, Zeng R, Gorodeski GI. Anti-apoptotic effects of estrogen in normal and in cancer human cervical epithelial cells. Endocrinology 145:5568-79 (2004)
- Wang Q, Wang L, Feng YH, Li X, Zeng R, Gorodeski GI. P2X7-receptor-mediated apoptosis of human cervical epithelial cells. Am J Physiol Cell Physiol. 287:C1349-58 (2004)
- Wang L, Feng YH, Gorodeski GI. EGF facilitates epinephrine inhibition of P2X7-receptor pore formation by modulating 2-adrenoceptor internalization and recycling: a signaling network. Endocrinology 146:164-74 (2005)
- Feng YH, Zhou LY, Sun Y, and Douglas JG. Functional Diversity of AT2 Receptor Orthologues in Closely related Eutherian. Kidney Intl 67:1731-8 (2005)
- eng YH, Wang L, Wang Q, Li X, Zeng R, Gorodeski GI. ATP ligation stimulates GRK-3 - mediated phosphorylation and -arrestin-2- and dynamin-dependent internalization of the P2X7-receptor. Am J Physiol Cell Physiol. 288:C1342-56 (2005)
- Feng YH, Zhou L, Qiu R, and Robin Zeng. Single mutations at Asn295 and Leu305 in the cytoplasmic half of TM7 of the AT1 receptor induce promiscuous agonist specificity for angiotensin II fragments - A PSEUDO-CONSTITUTIVE ACTIVITY. Mol Pharmacol 68:347-55 (2005)
- Feng YH, Ding Y, Ren S, Xu C, Karnik SS. Unconventional homologous internalization of the AT1 receptor induced by G protein-independent signals. Hypertension 46:419-25 (2005)
- Feng YH, Li X, Wang L, Zhou L, Gorodeski GI. A truncated P2X7 receptor variant (P2X7-j) endogenously expressed in cervical cancer cells antagonizes the full-length P2X7 receptor through hetero-oligomerization. J Biol Chem. 281:17228-37 (2006)
Sergey Iordanskiy, Ph.D.
Name: Sergey Iordanskiy, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Assistant Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Molecular biology of retroviruses & retroelements; Effect of radiation-induced cellular stress on virus latency, replication and cellular response; Exosomes in intercellular communication and cytopathogenesis.
Lentiviral vectors for delivery and expression of genome editing tools; Coinfection of HIV and human blood parasites.
Email:
Office Phone:
(301) 295-0580
Department Website:
Education
B.S & M.S., Biochemistry, Moscow State University of Education, Moscow, Russia
Ph.D., Cellular Biology, Moscow State University of Education & Ivanovsky Research Institute of Virology, Russian Academy of Medical Sciences
Postdoctoral Training, Molecular Biology of AIDS, Picower Institute for Medical Research, Manhasset, NY
Postdoctoral Training, Molecular Virology, George Washington University, Washington, DC
Ph.D., Cellular Biology, Moscow State University of Education & Ivanovsky Research Institute of Virology, Russian Academy of Medical Sciences
Postdoctoral Training, Molecular Biology of AIDS, Picower Institute for Medical Research, Manhasset, NY
Postdoctoral Training, Molecular Virology, George Washington University, Washington, DC
Biography
RESEARCH DESCRIPTION:
My laboratory studies the molecular mechanisms of innate immune response to radiation-induced stress and involvement of the endogenous retroviruses and retroelements in this response. Even mild radiation doses may induce prolonged or chronic inflammation that disrupts organ functions. This is an important factor of secondary radiation-related disorders, such as vascular abnormalities, neuronal damage, autoimmune diseases and radiation-related cancer. We consider molecular patterns associated with viral infections, such as viral RNAs and proteins as the essential factors that modulate and exacerbate radiation-induced inflammation.
Ongoing Projects:
Radiation-induced cellular stress and human endogenous retroviruses
Human endogenous retroviruses (HERVs) constitute 8.3% of our genome. Most of integrated HERV genomes are silenced. However, detection of high levels of HERV-K mRNA, proteins, and even viral particles in a wide range of embryonic cells and cancers suggests that some HERVs may play an essential role in cell differentiation and cancer development. Recent studies revealed transcriptional activation of some retroviral genomes in various cancers and immune cells after exposure to radiation doses. We investigate the effect of gamma radiation on the expression of human endogenous retroviruses and their impact on inflammatory response in various types of immune cells. We found that promoters of certain HERV genomes become permanently activated after the single doses of radiation. Retroviral RNA, as well as some viral proteins, particularly Env (envelope protein), affect innate immune response and can enhance radiation-induced inflammation via the activation of critical pathways. Our ultimate goal is to elucidate the retrovirus-related mechanisms that enhance radiation-induced inflammation and indirect pathogenic effect of radiation on unexposed cells. Our long term goal is to reduce the inflammatory response to ionizing radiation using reprogramming cytokine profile of radiation-activated cells from pro- to anti-inflammatory phenotype via the modulation of expression of endogenous retroelements.
Exosomes in cytopathogenesis and intercellular communications within context of radiation-induced stress.
Initially small extracellular vesicles, exosomes, were thought to be a mechanism for discarding unwanted cellular material. However, in recent years, numerous evidence has indicated the role of exosomes in intercellular communication and the progression of various pathologies, including cancer and multiple neurodegenerative disorders. Exosomes are cell-derived vesicles that are present in all biological fluids and are capable of carrying RNAs and proteins which can be exchanged from cell-to-cell. Existing data indicate that exosomes and their cargo play crucial roles in communicating of radiation-induced and bystander cells with the result related to DNA damage and cell pathogenesis. We recently demonstrated multiple pathogenic effects of exosomes from the cells containing integrated retroviral genomes, such as human T lymphotropic virus 1 (HTLV-1) and HIV-1 on naïve cells. These effects were enhanced by the exposure of producing cells to ionizing radiation. Current research in our laboratory is focused on the analysis of host-cellular and viral cargo in the exosomes released from the radiation-exposed cells. We also investigate how non radiation-exposed cells respond to exosome-mediated effect of radiation in the context of radiotherapy and environmental radiation. Potential outcomes include understanding of the functions of exosome-packaged noncoding RNAs and mRNA, viral and host proteins in recipient cells and their pathogenic impact that is related to radiation. Identification of exosome-incorporated biomarkers of radiation doses is also part of this study.
Collaborative Projects
Our laboratory is involved in collaborative projects with George Washington University (Paul Brindley Lab) and Massachusetts Institute of Technology (Kevin Esvelt Lab). These studies are related to coinfection of HIV and human blood fluke Schistosoma mansoni and S. hematobium and the use of HIV-based lentiviral vectors for delivery of gene editing tools within the context of Gene Drive strategy.
My laboratory studies the molecular mechanisms of innate immune response to radiation-induced stress and involvement of the endogenous retroviruses and retroelements in this response. Even mild radiation doses may induce prolonged or chronic inflammation that disrupts organ functions. This is an important factor of secondary radiation-related disorders, such as vascular abnormalities, neuronal damage, autoimmune diseases and radiation-related cancer. We consider molecular patterns associated with viral infections, such as viral RNAs and proteins as the essential factors that modulate and exacerbate radiation-induced inflammation.
Ongoing Projects:
Radiation-induced cellular stress and human endogenous retroviruses
Human endogenous retroviruses (HERVs) constitute 8.3% of our genome. Most of integrated HERV genomes are silenced. However, detection of high levels of HERV-K mRNA, proteins, and even viral particles in a wide range of embryonic cells and cancers suggests that some HERVs may play an essential role in cell differentiation and cancer development. Recent studies revealed transcriptional activation of some retroviral genomes in various cancers and immune cells after exposure to radiation doses. We investigate the effect of gamma radiation on the expression of human endogenous retroviruses and their impact on inflammatory response in various types of immune cells. We found that promoters of certain HERV genomes become permanently activated after the single doses of radiation. Retroviral RNA, as well as some viral proteins, particularly Env (envelope protein), affect innate immune response and can enhance radiation-induced inflammation via the activation of critical pathways. Our ultimate goal is to elucidate the retrovirus-related mechanisms that enhance radiation-induced inflammation and indirect pathogenic effect of radiation on unexposed cells. Our long term goal is to reduce the inflammatory response to ionizing radiation using reprogramming cytokine profile of radiation-activated cells from pro- to anti-inflammatory phenotype via the modulation of expression of endogenous retroelements.
Exosomes in cytopathogenesis and intercellular communications within context of radiation-induced stress.
Initially small extracellular vesicles, exosomes, were thought to be a mechanism for discarding unwanted cellular material. However, in recent years, numerous evidence has indicated the role of exosomes in intercellular communication and the progression of various pathologies, including cancer and multiple neurodegenerative disorders. Exosomes are cell-derived vesicles that are present in all biological fluids and are capable of carrying RNAs and proteins which can be exchanged from cell-to-cell. Existing data indicate that exosomes and their cargo play crucial roles in communicating of radiation-induced and bystander cells with the result related to DNA damage and cell pathogenesis. We recently demonstrated multiple pathogenic effects of exosomes from the cells containing integrated retroviral genomes, such as human T lymphotropic virus 1 (HTLV-1) and HIV-1 on naïve cells. These effects were enhanced by the exposure of producing cells to ionizing radiation. Current research in our laboratory is focused on the analysis of host-cellular and viral cargo in the exosomes released from the radiation-exposed cells. We also investigate how non radiation-exposed cells respond to exosome-mediated effect of radiation in the context of radiotherapy and environmental radiation. Potential outcomes include understanding of the functions of exosome-packaged noncoding RNAs and mRNA, viral and host proteins in recipient cells and their pathogenic impact that is related to radiation. Identification of exosome-incorporated biomarkers of radiation doses is also part of this study.
Collaborative Projects
Our laboratory is involved in collaborative projects with George Washington University (Paul Brindley Lab) and Massachusetts Institute of Technology (Kevin Esvelt Lab). These studies are related to coinfection of HIV and human blood fluke Schistosoma mansoni and S. hematobium and the use of HIV-based lentiviral vectors for delivery of gene editing tools within the context of Gene Drive strategy.
Representative publications, projects, and/or deployments
- Barclay RA, Schwab A, DeMarino C, Akpamagbo Y, Lepene B, Kassaye S, Iordanskiy S and F. Kashanchi. Exosomes from uninfected cells activate transcription of latent HIV-1. J Biol Chem. 2017 292(28):11682-11701; PMID: 28536264
- Akpamagbo YA, DeMarino C, Pleet ML, Schwab A, Rodriguez M, Barclay RA, Sampey G, Iordanskiy S, El-Hage N and F Kashanchi. HIV-1 Transcription Inhibitors Increase the Synthesis of Viral Non-Coding RNA that Contribute to Latency. Curr Pharm Des. 2017; 23(28):4133-4144. PMID: 28641535.
- Pleet ML, Mathiesen A, DeMarino C, Akpamagbo YA, Barclay RA, Schwab A, Iordanskiy S, Sampey GC, Lepene B, Nekhai S, Aman MJ and F Kashanchi. Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction. Front Microbiol. 2018; 9:692.. PMID: 29696006.
Bibliography
Biosketch Link:
- Suttiprapa S, Rinaldi G, Tsai IJ, Mann VH, Dubrovsky L, Yan HB, Holroyd N, Huckvale T, Durrant C, Protasio AV, Pushkarsky T, Iordanskiy S, Berriman M, Bukrinsky MI and PJ Brindley, HIV-1 Integrates Widely throughout the Genome of the Human Blood Fluke Schistosoma mansoni. PLoS Pathog. 2016 Oct 20;12(10):e1005931.
- Santos S, Obukhov Y, Nekhai S, Pushkarsky T, Brichacek B, Bukrinsky M and S Iordanskiy. Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells, Virology. 2016 Oct;497:11-22.
- Iordanskiy S and F Kashanchi, Potential of radiation-induced cellular stress for reactivation of latent HIV-1 and killing of infected cells. AIDS Res Hum Retroviruses. 2016 32(2):120-124.
- Sampey G, Saifuddin M, Schwab A, Barclay R, Punya S, Chung M-Y, Hakami RM, Asad Zadeh M, Lepene B, Klase ZA, El-Hage N, Young M, Iordanskiy S and F Kashanchi, Exosomes from HIV-1 infected cells stimulate production of pro-inflammatory cytokines through TAR RNA. J Biol Chem. 2016 291(3):1251-1266.
- Iordanskiy S, Van Duyne R, Sampey GC, Woodson CM, Fry K, Saifuddin M, Guo J, Wu Y, Romerio F and F Kashanchi, Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells. Virology 2015, 485:1–15.
- Guendel I, Iordanskiy S, Van Duyne R, Kehn-Hall K, Saifuddin M, Das R, Jaworski E, Sampey G, Senina S, Shultz L, Narayanan A, Chen H, Lepene B, Zeng C, and F. Kashanchi, Novel neuroprotective GSK-3β inhibitor restricts Tat-mediated HIV-1 replication. J Virol 2014, 88(2): 1189-1208
- Narayanan A, Iordanskiy S, Das R, Van Duyne R, Santos S, Jaworski E, Guendel I, Sampey G, Gerhart E, Iglesias-Ussel M, Popratiloff A, Hakami R, Kehn-Hall K, Young M, Subra C, Gilbert C, Bailey C, Romerio F and F. Kashanchi, Exosomes derived from HIV-1 infected cells contain TAR RNA. J Biol Chem. 2013 288(27): 20014-20033.
- Santos S, Obukhov Y, Nekhai S, Bukrinsky M and S Iordanskiy, Virus-producing cells determine the host protein profiles of HIV-1 virion cores. Retrovirology. 2012, 9:65.
- Iordanskiy S, Berro R, Altieri M, Kashanchi F. and M. Bukrinsky, Intracytoplasmic maturation of the human immunodeficiency virus type 1 reverse transcription complexes determines their capacity to integrate into chromatin. Retrovirology 2006. 3: 4
- Iordanskiy S, Zhao Y, DiMarzio P, Agostini I, Dubrovsky L, and M. Bukrinsky, Heat-shock protein 70 exerts opposing effects on Vpr-dependent and Vpr-independent HIV-1 replication in macrophages. Blood. 2004. 104: 1867-1872.
Robert L Kortum, M.D., Ph.D.
Name: Robert L Kortum, M.D., Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Assistant Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Cancer Cell Signaling
Ras
Email:
Office Phone:
(301) 295-3249
Department Website:
Education
Ph.D. - University of Nebraska Medical School, 2004
M.D. - University of Nebraska Medical School, 2006
M.D. - University of Nebraska Medical School, 2006
Bibliography
Biosketch Link:
Frank Shewmaker, Ph.D.
Name: Frank Shewmaker, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Assistant Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Molecular and Cell Biology Graduate Program
Email:
Office Phone:
(301) 295-3527
Education
B.S., Biochemistry, Auburn University
Ph.D., Biochemistry, Tulane University
Post-Doctoral Training, Laboratory of Biochemistry & Genetics, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health (NIH)
Ph.D., Biochemistry, Tulane University
Post-Doctoral Training, Laboratory of Biochemistry & Genetics, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health (NIH)
Bibliography
Biosketch Link:
Andrew L Snow, Ph.D.
Name: Andrew L Snow, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Associate Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
human immunology, lymphocyte signaling & apoptosis, primary immune disorders
Email:
Office Phone:
(301) 295-3267
Education
B.S., Biology, Visual Arts, Duke University
Ph.D., Immunology, Stanford University School of Medicine
Postdoctoral Training, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH
Ph.D., Immunology, Stanford University School of Medicine
Postdoctoral Training, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH
Biography
RESEARCH INTERESTS
The major emphasis of my laboratory is to elucidate how aberrations in lymphocyte signaling contribute to deranged immune homeostasis in novel lymphoproliferative disorders and primary immunodeficiencies. Our research focuses on identifying novel molecular regulators of lymphocyte apoptosis and differentiation in humans, with the ultimate goal of informing new therapeutic approaches for controlling immune responses by manipulating cell death sensitivity.
ONGOING PROJECTS
1. Signal regulation and physiological relevance of specific T cell apoptosis pathways
The regulation and eventual contraction of activated T cells during an immune response is critical for maintaining equilibrium in the immune system and preventing unwanted damage to host tissues. Normally, specific apoptosis programs induced by T cell receptor (TCR) restimulation or cytokine withdrawal work to cull the majority of activated effector T cells, leaving a small pool of memory T cells behind to protect against subsequent infections (Fig 1). We now appreciate that genetic defects in lymphocyte apoptosis directly contribute to excess lymphoproliferation in humans. For example, T cells from patients with X-linked lymphoproliferative disease (XLP-1) display a profound defect in T cell receptor restimulation-induced cell death (RICD; also known as activation-induced cell death), a critical self-regulatory apoptosis program that constrains effector T cell expansion. Our lab has defined several biochemical mechanisms by which signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), which is lost or mutated in XLP patients, facilitates RICD. Most recently, we led an international collaborative effort demonstrating that inhibition of diacylglycerol kinase alpha (DGKa), a modulatory enzyme with elevated activity in SAP-deficient T cells, presents a viable therapeutic approach for treating EBV-induced fulminant mononucleosis in XLP-1 patients, via restoration of RICD. Collectively, this work underscores the physiological relevance of RICD in preventing excessive T cell accumulation, severe immunopathology and mortality in XLP patients infected with EBV. We continue to investigate how RICD sensitivity is “tuned” via SAP-dependent signals.
We are also investigating novel links between metabolic programming and apoptosis sensitivity in human T cells. Our recent work indicates that while excessive anabolic metabolism (i.e. glycolysis) leaves effector T cells more susceptible to RICD, catabolic metabolism (i.e. autophagy) can protect T cells derived from distinct memory compartments from death induced by cytokine withdrawal. We have delineated specific molecular mechanisms responsible for these changes in cell death sensitivity, and continue to investigate how specific metabolic programs affect T cell viability. Our work illuminates how metabolic changes govern T cell survival, and may explain why certain memory T cells give rise to a larger, more robust effector response (via reduced cell death) that better protects the host when challenged with a pathogen or tumor.
2. Novel immunological disorders linked to mutations in CARD11
We discovered that gain-of-function (GOF) mutations in the CARD11 gene cause a rare congenital B cell lymphoproliferative disorder called B cell Expansion with NF-kB and T cell Anergy (BENTA) disease. My laboratory has taken a leading role in the genetic diagnosis and phenotypic characterization of an expanding cohort of BENTA patients (Fig 2). CARD11 encodes a scaffolding protein that links antigen receptor signaling to NF-kB activation in lymphocytes. Unlike the wild-type protein, CARD11 GOF mutants spontaneously oligomerize and drive constitutive activation of NF-kB, contributing to increased proliferation and enhanced survival of both immature and naïve patient B cells. Surprisingly, BENTA patients also exhibit hallmarks of immunodeficiency, including B cell differentiation defects, selective antibody deficiency, and opportunistic viral infections (e.g. molluscum contagiousum, chronic EBV) that reflect impaired T cell responses. Our latest findings pinpoint intrinsic molecular defects in plasma cell differentiation and antibody secretion in activated BENTA patient B cells, despite profound apoptosis resistance that likely explains excessive B cell expansion.
In collaboration with Dr. Joshua Milner (NIH) and others, we are also investigating loss-of-function (LOF) CARD11 mutations in atopic patients with severe eczema. We recently described 4 families with distinct, hypomorphic CARD11 mutations that dominantly interfere with WT CARD11 signaling, resulting in impaired NF-kB and mTORC1 signaling. Extensive structure-function studies of the CARD11 molecule continue in my lab, drawing from an expanding list of natural mutations in human patients. Using cell transfection systems, murine models and primary patient lymphocytes, my lab also continues to investigate how both GOF and LOF CARD11 mutations perturb signaling, differentiation and function of B and T cells.
The major emphasis of my laboratory is to elucidate how aberrations in lymphocyte signaling contribute to deranged immune homeostasis in novel lymphoproliferative disorders and primary immunodeficiencies. Our research focuses on identifying novel molecular regulators of lymphocyte apoptosis and differentiation in humans, with the ultimate goal of informing new therapeutic approaches for controlling immune responses by manipulating cell death sensitivity.
ONGOING PROJECTS
1. Signal regulation and physiological relevance of specific T cell apoptosis pathways
The regulation and eventual contraction of activated T cells during an immune response is critical for maintaining equilibrium in the immune system and preventing unwanted damage to host tissues. Normally, specific apoptosis programs induced by T cell receptor (TCR) restimulation or cytokine withdrawal work to cull the majority of activated effector T cells, leaving a small pool of memory T cells behind to protect against subsequent infections (Fig 1). We now appreciate that genetic defects in lymphocyte apoptosis directly contribute to excess lymphoproliferation in humans. For example, T cells from patients with X-linked lymphoproliferative disease (XLP-1) display a profound defect in T cell receptor restimulation-induced cell death (RICD; also known as activation-induced cell death), a critical self-regulatory apoptosis program that constrains effector T cell expansion. Our lab has defined several biochemical mechanisms by which signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), which is lost or mutated in XLP patients, facilitates RICD. Most recently, we led an international collaborative effort demonstrating that inhibition of diacylglycerol kinase alpha (DGKa), a modulatory enzyme with elevated activity in SAP-deficient T cells, presents a viable therapeutic approach for treating EBV-induced fulminant mononucleosis in XLP-1 patients, via restoration of RICD. Collectively, this work underscores the physiological relevance of RICD in preventing excessive T cell accumulation, severe immunopathology and mortality in XLP patients infected with EBV. We continue to investigate how RICD sensitivity is “tuned” via SAP-dependent signals.
We are also investigating novel links between metabolic programming and apoptosis sensitivity in human T cells. Our recent work indicates that while excessive anabolic metabolism (i.e. glycolysis) leaves effector T cells more susceptible to RICD, catabolic metabolism (i.e. autophagy) can protect T cells derived from distinct memory compartments from death induced by cytokine withdrawal. We have delineated specific molecular mechanisms responsible for these changes in cell death sensitivity, and continue to investigate how specific metabolic programs affect T cell viability. Our work illuminates how metabolic changes govern T cell survival, and may explain why certain memory T cells give rise to a larger, more robust effector response (via reduced cell death) that better protects the host when challenged with a pathogen or tumor.
2. Novel immunological disorders linked to mutations in CARD11
We discovered that gain-of-function (GOF) mutations in the CARD11 gene cause a rare congenital B cell lymphoproliferative disorder called B cell Expansion with NF-kB and T cell Anergy (BENTA) disease. My laboratory has taken a leading role in the genetic diagnosis and phenotypic characterization of an expanding cohort of BENTA patients (Fig 2). CARD11 encodes a scaffolding protein that links antigen receptor signaling to NF-kB activation in lymphocytes. Unlike the wild-type protein, CARD11 GOF mutants spontaneously oligomerize and drive constitutive activation of NF-kB, contributing to increased proliferation and enhanced survival of both immature and naïve patient B cells. Surprisingly, BENTA patients also exhibit hallmarks of immunodeficiency, including B cell differentiation defects, selective antibody deficiency, and opportunistic viral infections (e.g. molluscum contagiousum, chronic EBV) that reflect impaired T cell responses. Our latest findings pinpoint intrinsic molecular defects in plasma cell differentiation and antibody secretion in activated BENTA patient B cells, despite profound apoptosis resistance that likely explains excessive B cell expansion.
In collaboration with Dr. Joshua Milner (NIH) and others, we are also investigating loss-of-function (LOF) CARD11 mutations in atopic patients with severe eczema. We recently described 4 families with distinct, hypomorphic CARD11 mutations that dominantly interfere with WT CARD11 signaling, resulting in impaired NF-kB and mTORC1 signaling. Extensive structure-function studies of the CARD11 molecule continue in my lab, drawing from an expanding list of natural mutations in human patients. Using cell transfection systems, murine models and primary patient lymphocytes, my lab also continues to investigate how both GOF and LOF CARD11 mutations perturb signaling, differentiation and function of B and T cells.
Bibliography
Biosketch Link:
- Voss K, Larsen SE, Snow AL. 2017. Metabolic reprogramming and apoptosis sensitivity: defining the contours of a T cell response. Cancer Letters 408:190-96.
- Arjunaraja S, Nosé BD, Sukumar G, Lott NM, Dalgard CL, Snow AL. 2017. Intrinsic Plasma Cell Differentiation Defects in BENTA Patient B Cells. Frontiers in Immunology 8: 913.
- Larsen SE, Voss K, Laing ED, Snow AL. 2017. Differential cytokine withdrawal-induced death sensitivity of effector T cells derived from distinct human CD8+ memory subsets. Cell Death Discovery 3:17031.
- Ma CA, Stinson JR, Zhang Y, Abbott JK, Weinreich MA, Hauk PJ, Reynolds PR, Lyons JJ, Nelson CG, Ruffo E, Dorjbal B, Glauzy S, Stoddard J, Niemela J, Rosenzweig SD, McElwee JJ, DiMaggio T, Stone KD, Palma A, Oleastro M, Prieto E, Bernasconi A, Dubra G, Danielian S, Zaiat J, Marti M, Kim B, Cooper MA, Romberg N, Meffre E, Gelfand EW*, Snow AL*, Milner JD*. 2017. “Germline hypomorphic CARD11 mutations in severe atopic disease.” Nature Genetics 49:1192-1201.
- Larsen SE, Bilenkin A, Snow AL. 2017. Sensitivity to restimulation-induced cell death is linked to glycolytic metabolism in human T cells. Journal of Immunology 198: 147-55.
- Ruffo E, Malacarne V, Larsen SE, Das R, Patrussi L, Wulfing C, Biskup C, Schwartzberg PL, Baldari TC, Rubio I, Nichols KE*, Snow AL*, Baldanzi G*, Graziani A*. 2016. Inhibition of diacylglycerol kinase alpha restores TCR-induced diacylglycerol signaling and restimulation-induced cell death in XLP-1 T lymphocytes. Science Translational Medicine 8: 321ra7.
- Brohl AS, Stinson JR, Su HC, Badgett T, Jennings CD, Sukumar G, Sindiri S, Wang W, Moir S, Dalgard CL, Moscow JA, Khan J, Snow AL. 2015. Germline CARD11 mutation in a patient with severe congenital B cell lymphocytosis. Journal of Clinical Immunology, 35: 32-46. ePub Oct 2014.
- Katz G, Krummey SM, Larsen SE, Stinson JR, Snow AL. 2014. SAP facilitates recruitment and activation of LCK at NTB-A receptors during restimulation-induced cell death. Journal of Immunology 192: 4202-9.
- Snow AL, Xiao W, Chaigne-Delalande B, Pittaluga S, Stinson JR, Matthews HF, Lu W, Zheng L, Schmitz R, Jhavar S, Kuchen S, Lamborn IT, Jing H, Raffeld M, Su HC, Staudt LM, Lenardo MJ. 2012. Congenital B cell lymphocytosis explained by novel germline CARD11 mutations. Journal of Experimental Medicine 209: 2247-61.
- Snow AL, Marsh RA, Krummey SM, Roehrs P, Young LR, Zhang K, van Hoff J, Dhar D, Nichols KE, Filipovich AH, Su HC, Bleesing JJ, Lenardo MJ. 2009. Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency. Journal of Clinical Investigation 119: 2976-2989.
PHA - Radioprotectants
Regina M Day, Ph.D.
Name: Regina M Day, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Vice Chair
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Email:
Office Phone:
(301) 295-3236
Education
A.B. Smith College, Northampton, MA, USA
Ph.D. Tufts University, Boston, MA, USA
Ph.D. Tufts University, Boston, MA, USA
Biography
Introduction and overview:
My laboratory is dedicated to understanding normal tissue repair processes and how the repair process is altered in fibrotic remodeling. Normal tissue regeneration for wound healing is a critical focus of research for the military as well as for the medical field in general. The long term goal of my laboratory is to understand the mechanism of fibrotic repair and to identify therapeutic agents to prevent and/or treat this disease. The lung provides an excellent model system for investigation, since it is uniquely sensitive to chemicals and radiation that produce well-defined stages of injury, inflammation, attempted repair, and repair failure/remodeling. Lung fibrosis is a progressive disease with no treatments and poor prognosis. Our laboratory uses in vivo animal models and in vitro primary cell cultures to systematically elucidate the mechanisms of tissue regeneration and fibrotic remodeling at the molecular, biochemical, cellular, and tissue levels.
Radiation countermeasures for the lung and hematopoietic systems and radiation biology:
• Radiation countermeasures for both the hematopoietic and lung tissues. Radiation-induced lung injury is a late effect of radiation, whereas hematopoietic injuries are an acute radiation injury. Because of the Department of Defense’s interest in protection against both acute and delayed injuries, we were requested to develop a murine model for both the hematopoietic and pulmonary injuries, and to test radiation countermeasures in both systems. My laboratory developed an animal model system incorporating both hematopoietic and lung radiation injuries. We have determined the mechanism of action of captopril protection in both tissues, as a part of the requirement for radiation countermeasure development under the Animal Rule for the FDA. We are currently expanding our testing of captopril in the minipig model of radiation acute injuries.
• My laboratory developed a cell culture system for studying the molecular mechanisms of radiation-induced senescence in normal (non-transformed, non-immortalized) cells. Our research demonstrated for the first time that normal lung and skin cells primarily undergo accelerated senescence, and not apoptosis, in response to radiation. We identified an early cellular response to radiation is the induction of insulin-like growth factor 1 (IGF-1) and the activation of its receptor (IGF-1R). These novel and provocative observations prompted us to hypothesize that senescence is the precipitating state for radiation pathology.
Hepatocyte growth factor (HGF) signaling for tissue repair and suppression of fibrosis:
• My laboratory has identified novel signaling pathways for HGF-induced normal tissue repair mechanisms. HGF expression is required for normal tissue repair, and HGF can redirect repair away from fibrotic remodeling to induce normal tissue regrowth. To understand how HGF can accomplish this, my research team investigated signal transduction mechanisms for HGF suppression of apoptosis in epithelial and endothelial cells that is induced during fibrosis. We next investigated the mechanisms by which HGF expression is suppressed during fibrotic remodeling. We recently uncovered a novel mechanism by which miRNA regulates HGF mRNA half-life under fibrotic conditions. This research led to the identification of potential novel anti-fibrotic treatment strategies.
• My laboratory developed a synthetic peptide based on other proteins that bind the HGF receptor, MET. The structural complexity of the full length HGF structure has prevented its development as a pharmaceutical agent, and full length HGF has not been successfully produced in sufficient quantities for clinical use. A patent was submitted by the USU/HJF JOTT based on these findings. Our laboratory currently aims to improve the design of this protein, to improve stability and increase receptor affinity.
My laboratory is dedicated to understanding normal tissue repair processes and how the repair process is altered in fibrotic remodeling. Normal tissue regeneration for wound healing is a critical focus of research for the military as well as for the medical field in general. The long term goal of my laboratory is to understand the mechanism of fibrotic repair and to identify therapeutic agents to prevent and/or treat this disease. The lung provides an excellent model system for investigation, since it is uniquely sensitive to chemicals and radiation that produce well-defined stages of injury, inflammation, attempted repair, and repair failure/remodeling. Lung fibrosis is a progressive disease with no treatments and poor prognosis. Our laboratory uses in vivo animal models and in vitro primary cell cultures to systematically elucidate the mechanisms of tissue regeneration and fibrotic remodeling at the molecular, biochemical, cellular, and tissue levels.
Radiation countermeasures for the lung and hematopoietic systems and radiation biology:
• Radiation countermeasures for both the hematopoietic and lung tissues. Radiation-induced lung injury is a late effect of radiation, whereas hematopoietic injuries are an acute radiation injury. Because of the Department of Defense’s interest in protection against both acute and delayed injuries, we were requested to develop a murine model for both the hematopoietic and pulmonary injuries, and to test radiation countermeasures in both systems. My laboratory developed an animal model system incorporating both hematopoietic and lung radiation injuries. We have determined the mechanism of action of captopril protection in both tissues, as a part of the requirement for radiation countermeasure development under the Animal Rule for the FDA. We are currently expanding our testing of captopril in the minipig model of radiation acute injuries.
• My laboratory developed a cell culture system for studying the molecular mechanisms of radiation-induced senescence in normal (non-transformed, non-immortalized) cells. Our research demonstrated for the first time that normal lung and skin cells primarily undergo accelerated senescence, and not apoptosis, in response to radiation. We identified an early cellular response to radiation is the induction of insulin-like growth factor 1 (IGF-1) and the activation of its receptor (IGF-1R). These novel and provocative observations prompted us to hypothesize that senescence is the precipitating state for radiation pathology.
Hepatocyte growth factor (HGF) signaling for tissue repair and suppression of fibrosis:
• My laboratory has identified novel signaling pathways for HGF-induced normal tissue repair mechanisms. HGF expression is required for normal tissue repair, and HGF can redirect repair away from fibrotic remodeling to induce normal tissue regrowth. To understand how HGF can accomplish this, my research team investigated signal transduction mechanisms for HGF suppression of apoptosis in epithelial and endothelial cells that is induced during fibrosis. We next investigated the mechanisms by which HGF expression is suppressed during fibrotic remodeling. We recently uncovered a novel mechanism by which miRNA regulates HGF mRNA half-life under fibrotic conditions. This research led to the identification of potential novel anti-fibrotic treatment strategies.
• My laboratory developed a synthetic peptide based on other proteins that bind the HGF receptor, MET. The structural complexity of the full length HGF structure has prevented its development as a pharmaceutical agent, and full length HGF has not been successfully produced in sufficient quantities for clinical use. A patent was submitted by the USU/HJF JOTT based on these findings. Our laboratory currently aims to improve the design of this protein, to improve stability and increase receptor affinity.
Representative publications, projects, and/or deployments
- 12/2016 – present Vice Chair USUHS School of Medicine Department of Pharmacology and Molecular Therapeutics
- 7/2014- present Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 11/2014 Adjunct Professor Georgetown University School of Medicine Pulmonary, Critical Care, and Sleep Medicine
- 2/2010- 7/2014 Associate Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 7/2004-1/2010 Tenure Track Assistant Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 1/2004-6/2004 Research Assistant Professor Georgetown Univ. School of Medicine Pulmonary, Critical Care, and Sleep Medicine
- 8/1999-12/2004 Research Assistant Professor Tufts-New England Medical Ctr Pulmonary, Critical Care, and Sleep Medicine Div
- Postdoctoral Fellow NIH, NCI, Lab of Cellular, Molecular Biology
Bibliography
- Landauer, M.R., Harvey, A.J., Kaytor, M.D., Day, R.M. (2019) Mechanism and therapeutic window of a genistein nanosuspension to protect against hematopoietic-acute radiation syndrome. J. Radiat. Res. In press.
- McCart, E.A., Lee, Y.H., Jha, J., Mungunsukh, O., Rittase, W.B., Summers, T.A., Muir, J., Day R.M. (2019) Delayed captopril administration mitigates hematopoietic injury in a murine model of total body irradiation. Sci Reports, 9: 2198.
- Bylicky, M.A., Mueller, G.P., Day, R.M. (2019) Radiation resistance of normal human astrocytes: role of non-homologous end joining DNA repair activity. J Radiat Res. 60: 37-50.
- Corey, S.J., Jha, J., McCart, E.A., Rittase, W.B., George, J., Mattapallil, J.J., Mehta, H., Ognoon, M., Bylicky, M.A., Summers, T.A., Day, R.M. (2018) Captopril mitigates splenomegaly and myelofibrosis in the Gata1low murine model of myelofibrosis. J Cell Mol Med, 22: 4274-4282.
- Du, Y., Banas, R.A., McCart, E.A., George, J., Oakley, K., Han, Y., Landauer, M.R., Day, R.M. (2018) Effect of human amnion-derived multipotent progenitor cells on hematopoietic recovery after total body irradiation in C57BL/6 mice. Int J Radiat Res, 16:155-168.
- Zhao*, J., Day*, R.M., Jin, J-Y., Quint, L., Williams, H., Ferguson, C., Yan, L., King, M., Albsheer, A., Matuszak, M., Kong, S-M. (2017) Thoracic radiation-induced pleural effusion and risk factors in patients with lung cancer. Oncotarget, 8: 97623-32.
- McCart, E.A., Lombardini, E., Mog, S.R., Panganiban, R.A.M., Dickson, K.M., Mansur, R.A., Nagy, V., Kim, S-Y., Selwyn, R., Landauer, M.R., Darling, T.N., Day, R.M. (2017) Accelerated senescence in a murine model of radiation-induced skin injury. J Radiat Res, 58: 636-646.
- Brzezniak, C., Oronsky, B., Trepel, J., Summers, T.A. Jr., Cabrales, P., Lee, M.J., Day, R., Jha, S., Caroen, S, Zeman, K, Ferr,y L, Harmer, C, Oronsky, N, Lybeck, M, Lybeck, HE, Brown, JF, Reid, T.R., Carter, C.A. RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor. Case Rep Oncol. 2017;10:276-280.
- Mungunsukh, O., Lee, Y.H., Bottaro, D.P., Day, R.M. (2016) The hepatocyte growth factor isoform NK2 activates motogenesis and survival but not proliferation due to lack of Akt activation. Cell Signal, 28, 1114-23.
- Barshishat-Kupper, M., McCart E.A., Freedy, J.G., Tipton A.J., Nagy V., Kim, S.-Y., Landauer, M.R., Mueller G.P., Day R.M. (2015) Protein oxidation in the lungs of C57BL/6J mice following X-irradiation. Proteomes, 3, 249-265.
Sergey Iordanskiy, Ph.D.
Name: Sergey Iordanskiy, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Assistant Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Molecular biology of retroviruses & retroelements; Effect of radiation-induced cellular stress on virus latency, replication and cellular response; Exosomes in intercellular communication and cytopathogenesis.
Lentiviral vectors for delivery and expression of genome editing tools; Coinfection of HIV and human blood parasites.
Email:
Office Phone:
(301) 295-0580
Department Website:
Education
B.S & M.S., Biochemistry, Moscow State University of Education, Moscow, Russia
Ph.D., Cellular Biology, Moscow State University of Education & Ivanovsky Research Institute of Virology, Russian Academy of Medical Sciences
Postdoctoral Training, Molecular Biology of AIDS, Picower Institute for Medical Research, Manhasset, NY
Postdoctoral Training, Molecular Virology, George Washington University, Washington, DC
Ph.D., Cellular Biology, Moscow State University of Education & Ivanovsky Research Institute of Virology, Russian Academy of Medical Sciences
Postdoctoral Training, Molecular Biology of AIDS, Picower Institute for Medical Research, Manhasset, NY
Postdoctoral Training, Molecular Virology, George Washington University, Washington, DC
Biography
RESEARCH DESCRIPTION:
My laboratory studies the molecular mechanisms of innate immune response to radiation-induced stress and involvement of the endogenous retroviruses and retroelements in this response. Even mild radiation doses may induce prolonged or chronic inflammation that disrupts organ functions. This is an important factor of secondary radiation-related disorders, such as vascular abnormalities, neuronal damage, autoimmune diseases and radiation-related cancer. We consider molecular patterns associated with viral infections, such as viral RNAs and proteins as the essential factors that modulate and exacerbate radiation-induced inflammation.
Ongoing Projects:
Radiation-induced cellular stress and human endogenous retroviruses
Human endogenous retroviruses (HERVs) constitute 8.3% of our genome. Most of integrated HERV genomes are silenced. However, detection of high levels of HERV-K mRNA, proteins, and even viral particles in a wide range of embryonic cells and cancers suggests that some HERVs may play an essential role in cell differentiation and cancer development. Recent studies revealed transcriptional activation of some retroviral genomes in various cancers and immune cells after exposure to radiation doses. We investigate the effect of gamma radiation on the expression of human endogenous retroviruses and their impact on inflammatory response in various types of immune cells. We found that promoters of certain HERV genomes become permanently activated after the single doses of radiation. Retroviral RNA, as well as some viral proteins, particularly Env (envelope protein), affect innate immune response and can enhance radiation-induced inflammation via the activation of critical pathways. Our ultimate goal is to elucidate the retrovirus-related mechanisms that enhance radiation-induced inflammation and indirect pathogenic effect of radiation on unexposed cells. Our long term goal is to reduce the inflammatory response to ionizing radiation using reprogramming cytokine profile of radiation-activated cells from pro- to anti-inflammatory phenotype via the modulation of expression of endogenous retroelements.
Exosomes in cytopathogenesis and intercellular communications within context of radiation-induced stress.
Initially small extracellular vesicles, exosomes, were thought to be a mechanism for discarding unwanted cellular material. However, in recent years, numerous evidence has indicated the role of exosomes in intercellular communication and the progression of various pathologies, including cancer and multiple neurodegenerative disorders. Exosomes are cell-derived vesicles that are present in all biological fluids and are capable of carrying RNAs and proteins which can be exchanged from cell-to-cell. Existing data indicate that exosomes and their cargo play crucial roles in communicating of radiation-induced and bystander cells with the result related to DNA damage and cell pathogenesis. We recently demonstrated multiple pathogenic effects of exosomes from the cells containing integrated retroviral genomes, such as human T lymphotropic virus 1 (HTLV-1) and HIV-1 on naïve cells. These effects were enhanced by the exposure of producing cells to ionizing radiation. Current research in our laboratory is focused on the analysis of host-cellular and viral cargo in the exosomes released from the radiation-exposed cells. We also investigate how non radiation-exposed cells respond to exosome-mediated effect of radiation in the context of radiotherapy and environmental radiation. Potential outcomes include understanding of the functions of exosome-packaged noncoding RNAs and mRNA, viral and host proteins in recipient cells and their pathogenic impact that is related to radiation. Identification of exosome-incorporated biomarkers of radiation doses is also part of this study.
Collaborative Projects
Our laboratory is involved in collaborative projects with George Washington University (Paul Brindley Lab) and Massachusetts Institute of Technology (Kevin Esvelt Lab). These studies are related to coinfection of HIV and human blood fluke Schistosoma mansoni and S. hematobium and the use of HIV-based lentiviral vectors for delivery of gene editing tools within the context of Gene Drive strategy.
My laboratory studies the molecular mechanisms of innate immune response to radiation-induced stress and involvement of the endogenous retroviruses and retroelements in this response. Even mild radiation doses may induce prolonged or chronic inflammation that disrupts organ functions. This is an important factor of secondary radiation-related disorders, such as vascular abnormalities, neuronal damage, autoimmune diseases and radiation-related cancer. We consider molecular patterns associated with viral infections, such as viral RNAs and proteins as the essential factors that modulate and exacerbate radiation-induced inflammation.
Ongoing Projects:
Radiation-induced cellular stress and human endogenous retroviruses
Human endogenous retroviruses (HERVs) constitute 8.3% of our genome. Most of integrated HERV genomes are silenced. However, detection of high levels of HERV-K mRNA, proteins, and even viral particles in a wide range of embryonic cells and cancers suggests that some HERVs may play an essential role in cell differentiation and cancer development. Recent studies revealed transcriptional activation of some retroviral genomes in various cancers and immune cells after exposure to radiation doses. We investigate the effect of gamma radiation on the expression of human endogenous retroviruses and their impact on inflammatory response in various types of immune cells. We found that promoters of certain HERV genomes become permanently activated after the single doses of radiation. Retroviral RNA, as well as some viral proteins, particularly Env (envelope protein), affect innate immune response and can enhance radiation-induced inflammation via the activation of critical pathways. Our ultimate goal is to elucidate the retrovirus-related mechanisms that enhance radiation-induced inflammation and indirect pathogenic effect of radiation on unexposed cells. Our long term goal is to reduce the inflammatory response to ionizing radiation using reprogramming cytokine profile of radiation-activated cells from pro- to anti-inflammatory phenotype via the modulation of expression of endogenous retroelements.
Exosomes in cytopathogenesis and intercellular communications within context of radiation-induced stress.
Initially small extracellular vesicles, exosomes, were thought to be a mechanism for discarding unwanted cellular material. However, in recent years, numerous evidence has indicated the role of exosomes in intercellular communication and the progression of various pathologies, including cancer and multiple neurodegenerative disorders. Exosomes are cell-derived vesicles that are present in all biological fluids and are capable of carrying RNAs and proteins which can be exchanged from cell-to-cell. Existing data indicate that exosomes and their cargo play crucial roles in communicating of radiation-induced and bystander cells with the result related to DNA damage and cell pathogenesis. We recently demonstrated multiple pathogenic effects of exosomes from the cells containing integrated retroviral genomes, such as human T lymphotropic virus 1 (HTLV-1) and HIV-1 on naïve cells. These effects were enhanced by the exposure of producing cells to ionizing radiation. Current research in our laboratory is focused on the analysis of host-cellular and viral cargo in the exosomes released from the radiation-exposed cells. We also investigate how non radiation-exposed cells respond to exosome-mediated effect of radiation in the context of radiotherapy and environmental radiation. Potential outcomes include understanding of the functions of exosome-packaged noncoding RNAs and mRNA, viral and host proteins in recipient cells and their pathogenic impact that is related to radiation. Identification of exosome-incorporated biomarkers of radiation doses is also part of this study.
Collaborative Projects
Our laboratory is involved in collaborative projects with George Washington University (Paul Brindley Lab) and Massachusetts Institute of Technology (Kevin Esvelt Lab). These studies are related to coinfection of HIV and human blood fluke Schistosoma mansoni and S. hematobium and the use of HIV-based lentiviral vectors for delivery of gene editing tools within the context of Gene Drive strategy.
Representative publications, projects, and/or deployments
- Barclay RA, Schwab A, DeMarino C, Akpamagbo Y, Lepene B, Kassaye S, Iordanskiy S and F. Kashanchi. Exosomes from uninfected cells activate transcription of latent HIV-1. J Biol Chem. 2017 292(28):11682-11701; PMID: 28536264
- Akpamagbo YA, DeMarino C, Pleet ML, Schwab A, Rodriguez M, Barclay RA, Sampey G, Iordanskiy S, El-Hage N and F Kashanchi. HIV-1 Transcription Inhibitors Increase the Synthesis of Viral Non-Coding RNA that Contribute to Latency. Curr Pharm Des. 2017; 23(28):4133-4144. PMID: 28641535.
- Pleet ML, Mathiesen A, DeMarino C, Akpamagbo YA, Barclay RA, Schwab A, Iordanskiy S, Sampey GC, Lepene B, Nekhai S, Aman MJ and F Kashanchi. Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction. Front Microbiol. 2018; 9:692.. PMID: 29696006.
Bibliography
Biosketch Link:
- Suttiprapa S, Rinaldi G, Tsai IJ, Mann VH, Dubrovsky L, Yan HB, Holroyd N, Huckvale T, Durrant C, Protasio AV, Pushkarsky T, Iordanskiy S, Berriman M, Bukrinsky MI and PJ Brindley, HIV-1 Integrates Widely throughout the Genome of the Human Blood Fluke Schistosoma mansoni. PLoS Pathog. 2016 Oct 20;12(10):e1005931.
- Santos S, Obukhov Y, Nekhai S, Pushkarsky T, Brichacek B, Bukrinsky M and S Iordanskiy. Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells, Virology. 2016 Oct;497:11-22.
- Iordanskiy S and F Kashanchi, Potential of radiation-induced cellular stress for reactivation of latent HIV-1 and killing of infected cells. AIDS Res Hum Retroviruses. 2016 32(2):120-124.
- Sampey G, Saifuddin M, Schwab A, Barclay R, Punya S, Chung M-Y, Hakami RM, Asad Zadeh M, Lepene B, Klase ZA, El-Hage N, Young M, Iordanskiy S and F Kashanchi, Exosomes from HIV-1 infected cells stimulate production of pro-inflammatory cytokines through TAR RNA. J Biol Chem. 2016 291(3):1251-1266.
- Iordanskiy S, Van Duyne R, Sampey GC, Woodson CM, Fry K, Saifuddin M, Guo J, Wu Y, Romerio F and F Kashanchi, Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells. Virology 2015, 485:1–15.
- Guendel I, Iordanskiy S, Van Duyne R, Kehn-Hall K, Saifuddin M, Das R, Jaworski E, Sampey G, Senina S, Shultz L, Narayanan A, Chen H, Lepene B, Zeng C, and F. Kashanchi, Novel neuroprotective GSK-3β inhibitor restricts Tat-mediated HIV-1 replication. J Virol 2014, 88(2): 1189-1208
- Narayanan A, Iordanskiy S, Das R, Van Duyne R, Santos S, Jaworski E, Guendel I, Sampey G, Gerhart E, Iglesias-Ussel M, Popratiloff A, Hakami R, Kehn-Hall K, Young M, Subra C, Gilbert C, Bailey C, Romerio F and F. Kashanchi, Exosomes derived from HIV-1 infected cells contain TAR RNA. J Biol Chem. 2013 288(27): 20014-20033.
- Santos S, Obukhov Y, Nekhai S, Bukrinsky M and S Iordanskiy, Virus-producing cells determine the host protein profiles of HIV-1 virion cores. Retrovirology. 2012, 9:65.
- Iordanskiy S, Berro R, Altieri M, Kashanchi F. and M. Bukrinsky, Intracytoplasmic maturation of the human immunodeficiency virus type 1 reverse transcription complexes determines their capacity to integrate into chromatin. Retrovirology 2006. 3: 4
- Iordanskiy S, Zhao Y, DiMarzio P, Agostini I, Dubrovsky L, and M. Bukrinsky, Heat-shock protein 70 exerts opposing effects on Vpr-dependent and Vpr-independent HIV-1 replication in macrophages. Blood. 2004. 104: 1867-1872.
Juliann G. Kiang, M.A., Ph.D.
Name: Juliann G. Kiang, M.A., Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Adjunct Professor
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Molecular mechanism underlying Radiation and drug development for radiation combined injury
Polytrauma Injury
Email:
Office Phone:
(301) 295-1076
Department Website:
Education
Postdoctoral, University of California, Berkeley, CA 1984-1988
Ph.D. University of California, Berkeley, CA, 1983
M.A. University of Nebraska, Omaha, NE, 1977
B.S. FuJen Catholic University, Taipei, Taiwan, ROC, 1975
Ph.D. University of California, Berkeley, CA, 1983
M.A. University of Nebraska, Omaha, NE, 1977
B.S. FuJen Catholic University, Taipei, Taiwan, ROC, 1975
Biography
Dr. Juliann Kiang is a principal investigator at Armed Forces Radiobiology Research Institute (AFRRI). She is Adjunct Professor in Department of Pharmacology and Molecular Therapeutics and in Department of Medicine, School of Medicine, Uniformed Services University of the Health Sciences (USU).
Dr. Kiang serves in editorial boards of several scientific journals, NIH and VA study sections, and USU committees. She worked in Water Reed Army Institute of Research from 1989 to 2006 before joining AFRRI.
Dr. Kiang is involved in studies showing corticotrophin-releasing factor and heat shock proteins are capable of protecting against edema/inflammation and hypoxia injury, respectively. She demonstrates that overexpression of inducible form of heat shock protein 70 kDa induced by sublethal heat stress, chemical stimulation, or the gene transfer produces thermotolerance and cross-tolerance that may be related to an inhibition of changes in intracellular calcium concentrations and expression of stress-related genes and proteins such as inducible nitric oxide synthase and p38-MAPK. She has found 17-DMAG, mesenchymal stem cells, G-CSF, ghrelin, or ciprofloxacin that can make cells endure much better under circumstances of low oxygen, a way to treat heat stroke, ischemia, hemorrhage, cancer, heart attack, stroke, or ionizing radiation injury.
Dr. Kiang had made four major contributions in her research career (journal references to work are noted).
Dr. Kiang is the first to demonstrate that treatment with corticotrophin-releasing factor (CRF) inhibits neurogenic and thermally-induced protein extravasation in rats (9-14). She also found that urotensin I and sauvagine (members of the CRF superfamily) possess the same properties as CRF but with greater potency (15). She holds a patent resulting from this work. She has provided evidence that CRF and its analogs increase intracellular Ca2+ concentrations in vitro (33, 36, 50), which are correlated with capacity of these neuropeptides to inhibit thermally-induced edema (50). CRF exerts its action on CRF type 2 receptors to activate enzymes such as tyrosine kinases, phospholipase 1 and 2 to lead to a result of increases in intracellular Ca2+ concentrations (56). A patent is resulted.
Dr. Kiang’s second major contribution is that she performed extensive research to establish the effect of heat shock on components of signal transduction pathways, such as H+, Ca2+, Na+, cAMP, inositol 1,4,5-trisphosphate, and heat shock proteins in cultured cells. Her findings in this area are wide-ranging and have extended knowledge in the heat shock field (18, 19, 22, 25, 29, 40-42, 44, 46-48, 51-55, 57, 58, 60-62). Her findings provide insight to unfold the mechanisms of tolerance and cross-tolerance (64, 67). Heat shock protein 70 kDa plays a very important role in cell survival – a fine-line before occurrence of apoptosis.
Dr. Kiang’s third major contribution is that she has shown heat shock protein 70 kDa (HSP-70i) can protect the rat ileum from the ischemia/reperfusion injury (37, 66), ricin injury (47), during ileitis (57), and the mouse jejunum, lung, heart, and kidney from the hemorrhagic shock (70). She has also shown that down-regulation of inducible nitric oxide synthase inhibits the activity of caspase-3, an apoptotic protease, and overexpression of HSP-70i prevents ATP loss resulted from hemorrhage (78, 87, 91, 99, 104) or radiation-injury (106-108, 110-114). The work has resulted in a provisional patent.
Dr. Kiang’s fourth major contribution is that she has characterized radiation combined injury (110, 111, 115, 120) shown that ciprofloxacin (122, 126-128, 134), ghrelin (130, 146), and bone marrow mesenchymal stem cells (132, 140) can combat radiation injury combined with skin-wound injury. The research work is ongoing. Meanwhile, she established a new combined injury model of radiation with hemorrhage (135, 138, 142, 145) that brought her the 2016 AFRRI Research Award.
Bubliography
Peer-reviewed publications (149)
1. Kiang JG, Dewey WL, and Wei ET. Tolerance to morphine bradycardia in the rat. J. Pharmacol Exp. Ther. 226:187 192, 1983.
2. Kiang JG and Wei ET. Inhibition of an opiate-induced vagal reflex in rats by naloxone, SMS 201 995 and ICI 154, 129. Regulatory Peptides 6:255 262, 1983.
3. Dashwood MR, Kiang JG, and Wei ET. An etorphine-evoked reflex in rats is inhibited by naloxone, N-methylnaloxone, and SMS 201 995. Arch. Int. Pharmacodyn. Ther. 266:77 82, 1983.
4. Kiang JG and Wei ET. Sensitivity to morphine-evoked bradycardia in rats is modified by dynorphin (1 13), (Leu)enkephalin and (Met)enkephalin. J. Pharmacol. Exp. Ther. 229:469 473, 1984.
5. Kiang JG and Wei ET. Peripheral opioid receptors influencing heart rate in rats: evidence for endogenous tolerance. Regulatory Peptides 8:297 303, 1984.
6. Tang J, Webber RJ, Chang D, Chang JK, Kiang JG, and Wei ET. Depressor and natriuretic activities of several atrial peptides. Regulatory Peptides 9:543 549, 1984.
7. Wei ET and Kiang JG. Peripheral opioid receptors influencing heart rate in rats. In: Opioid Peptides in the Periphery. (Eds, F. Fraioli, A. Isidori and M. Mazzetti) Developments in Neuroscience 18:95 101, 1984, Amsterdam, Elsevier.
8. Kiang JG and Wei ET. CRF-evoked bradycardia in urethane-anesthetized rats is blocked by naloxone. Peptides 6:409 413, 1985.
9. Kiang JG and Wei ET. CRF: an inhibitor of neurogenic plasma extravasation produced by saphenous nerve stimulation. Eur. J. Pharmacol. 114:111 112, 1985.
10. Wei ET, Kiang JG, Buchan P, and Smith T. Corticotropin-releasing factor (CRF) inhibits neurogenic plasma extravasation in the rat paw. J. Pharmacol. Exp. Ther. 238:783 787, 1986.
11. Kiang JG and Wei ET. Corticotropin-releasing factor (CRF) inhibits thermal injury. J. Pharmacol. Exp. Ther. 243:517- 520, 1987.
12. Wei ET and Kiang JG. Inhibition of protein exudation from the trachea by corticotropin-releasing factor. Eur. J. Pharmacol. 140:63-67, 1987.
13. Wei ET, Kiang JG, and Tien JQ. Anti-inflammatory activity of corticotropin-releasing factor: I. Efficacy studies. Proc. West. Pharmacol. Soc. 30:59 62, 1987.
14. Kiang JG, Poree L, and Wei ET. Anti-inflammatory activity of corticotropin-releasing factor: II. Mechanisms of action. Proc. West. Pharmacol. Soc. 30:63 65, 1987.
15. Wei ET and Kiang JG. Peptides of the corticoliberin superfamily attenuate thermal and neurogenic inflammation in rat paw skin. Eur. J. Pharmacol. 168:81 86, 1989.
16. Kiang JG and Colden-Stanfield M. Morphine induces an intracellular alkalinization in bovine aortic endothelial cells (BAECs), In: International Narcotic Research Conference (INRC) '89. (Eds. R. Quirion, K. Jhamandas and C. Gianoulakis) Alan Liss Press, N.Y., Prog. Clin. Biol. Res. 328:137 140, 1989.
17. Wei ET, Wong JC, and Kiang JG. Decreased inflammatory responsiveness of hypophysectomized rats to heat is reversed by a CRF antagonist. Regulatory Peptides 27:317 323, 1990.
18. Kiang JG, McKinney LC, and Gallin EK. Heat induces an intracellular acidification in human A 431 cells: role of Na+/H+ exchanger and metabolism. Am. J. Physiol., 259(Cell Physiol. 28):C727-C737, 1990.
19. Kiang JG, Wu YY, and Lin M. Hyperthermia elevates cAMP levels in human epidermoid A 431 cells. Biochem. J. 276:683 689, 1991.
20. Kiang JG. Effect of intracellular pH on cytosolic free [Ca2+]i in A-431 cells. Eur. J. Pharmacol. 207(Molecular Pharmacol. Section):287-296, 1991.
21. Lin W-W, Kiang JG, and Chuang D-M. Pharmacological characterization of endothelin-stimulated phosphoinositides breakdown and cytosolic Ca2+ rise in C6 rat glioma cells. J. Neurosci., 12:1077 1085, 1992.
22. Kiang JG, Koenig ML, and Smallridge RC. Heat shock increases cytosolic free Ca2+ concentration via the Na+/Ca2+ exchange in human epidermoid A 431 cells. Am. J. Physiol. 263(Cell Physiol. 32):C30-38, 1992.
23. Smallridge RC, Gist ID, and Kiang JG. Na+-H+ antiport and monensin effects on cytosolic pH and iodide transport in FRTL 5 rat thyroid cells. Am. J. Physiol. 262(Endocrinol. Metab.) 25:E834-E839, 1992.
24. Smallridge RC, Kiang JG, Gist ID, Fein HG, and Galloway R. U 72133 inhibits TRH-induced activities in GH3 cells. Endocrinol. 131:1883 1888, 1992.
25. Kiang JG and McClain DE. Effect of heat shock, Ca2+, and cAMP on inositol 1,4,5-trisphosphate in human epidermoid A 431 cells. Am. J. Physiol. 264 (Cell Physiol. 33):C1561-C1569, 1993.
26. Aloj SM, Liguoro D, Kiang JG, and Smallridge RC. Purinergic (P2) receptor -operated calcium entry into rat thyroid cells. Biophy. Biochim. Res. Comm. 195:1-7, 1993.
27. Kiang JG. Corticotropin-releasing factor increases cytosolic free calcium via receptor-mediated Ca2+ channels. Eur. J. Pharmacol. (Molecular Pharmacol. Section) 267:135-142, 1994.
28. Kiang JG and Smallridge RC. Sodium cyanide increases cytosolic free calcium: Evidence of activation of the reversed mode of Na+/Ca2+ exchanger and Ca2+ mobilization from inositol trisphosphate-insensitive pools. Toxicol. Appl. Pharmacol., 127:173-181, 1994.
29. Kiang JG, Carr FE, Burns MR, and McClain DE. HSP-72 synthesis is promoted by increase in [Ca2+]i or activation of G proteins but not pHi or cAMP. Am. J. Physiol. 267 (Cell Physiol. 36):C104-C114, 1994.
30. Tang T, Kiang JG, and Cox BM. Opioids acting through delta-receptors increase the intracellular free calcium concentration in the dorsal root ganglion neuroblastoma hybrid ND8-47 cells. J. Pharmacol. Exptl. Ther., 270:40-46, 1994.
31. Wang X, Kiang JG, and Smallridge RC. U-73122 inhibits increases in inositol trisphosphates and cytosolic free [Ca2+] induced by TSH in FRTL-5 cells. Bioph. Biochim. Acta, 1223:101-106, 1994.
32. Poola I and Kiang JG. The estrogen inducible transferrin receptor-like membrane glycoprotein is related to stress regulated proteins. J. Biol. Chem. 269:1-8, 1994.
33. Kiang JG, Wang XD, and McClain DE. Corticotropin-releasing factor increases protein kinase C activity by elevating isoforms and at the membrane. Chin J. Physiol. 37:105-110, 1994.
34. Wang XD, Kiang JG, and Smallridge RC. Identification of protein kinase C and its multiple isoforms in Frtl-5 thyroid cells. Thyroid 5:137-140, 1995.
35. Tang T, Kiang JG, Cote T, and Cox BM. Opioid-induced increase [Ca2+]i in ND8-47 neuroblastoma X DRG hybrid cells is mediated through G protein-coupled delta opioid receptors and desensitized by chronic exposure to opioid. J. Neurochem. 65:1612-1621, 1995.
36. Kiang JG. Mystixin-7 and Mystixin-11 increase [Ca2+]i and inositol trisphosphates in human A-431 cells. Eur. J. Pharmacol. (Mol. Pharmacol. Section) 291:107-113, 1995.
37. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Heat shock protein 72 kD induction protects rat intestinal mucosa from ischemia/reperfusion injury. Gastroenterol. 109:505-515, 1995.
38. Tang T, Kiang JG, Cote T, and Cox BM. Antisense oligodeoxynucleotide to Gái2 protein á-subunit sequence inhibits an opioid-induced increase in intracellular free calcium in ND8-47 neuroblastoma x DRG hybrid cells. Mol. Pharmacol. 48:189-193, 1995.
39. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Rapid assay of HSF1 and HSF2 gene expression by reverse transcriptase PCR. Mol. Cell Biochem. 158: 48-51, 1996.
40. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Increases in HSF1 translocation and synthesis in human epidermoid A-431 cells: role of protein kinase C and [Ca2+]i. J. Investig. Med. 44:144-153, 1996.
41. Kiang JG, Ding XZ, and McClain DE. Thermotolerance attenuates heat-induced increases in [Ca2+]i and HSP-72 synthesis but not heat-induced intracellular acidification in human A-431 cells. J. Investig. Med. 44:189-192, 1996.
42. Kiang JG, Wang XD, Ding XZ, Gist I, and Smallridge RC. Heat shock inhibits the hypoxia-induced effects on iodide uptake and signal transduction and enhances cell survival in rat thyroid FRTL-5 cells. Thyroid, 6:475-483, 1996.
43. Wang XD, Kiang JG, Atwa MA, and Smallridge RC. Evidence for the involvement of protein kinase C isoforms in á-1 adrenergic activation of phospholipase A2 in Frtl-5 thyroid cells, J. Investig. Med. 44:566-574, 1996.
44. Kiang JG and Koenig ML. Characterization of intracellular calcium pools in thermotolerant and their desensitization in thermotolerant cells. J. Investig. Med. 44:352-361, 1996.
45. Kiang JG and Tsokos GC. Signal transduction and heat shock protein expression. J. Biomed. Sci. 3:379-388, 1996.
46. Ding XZ, Tsokos GC, Smallridge RC, and Kiang JG. Heat shock gene expression in HSP-70 and HSF1 gene-transfected human epidermoid A-431 cells. Mol. Cell. Biochem. 167:145-152, 1997.
47. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Induction of the heat shock response limits tissue injury during acute inflammation of the rat ileum. Critical Care Medicine 25:309-317, 1997.
48. Ding XZ, Tsokos GC, and Kiang JG. Heat shock factor 1 protein in heat shock factor 1 gene-transfected human epidermoid A-431 cells requires phosphorylation prior to inducing heat shock protein-70 production. J. Clin. Investig. 99:136-143, 1997.
49. Liossis S-N, Ding XZ, Kiang JG, and Tsokos GC. Overexpression of HSP70 offers thermoprotection but enhances the TCR/CD3- and Fas-induced apoptotic death in Jurkat T-cells. J. Immunol. 158:5668-5675, 1997.
50. Kiang JG. Corticotropin-releasing factor-like peptides increase cytosolic free calcium in human epidermoid A-431 cells. Eur. J. Pharmacol. (Molecular Pharmacology Section), 329:237-244, 1997.
51. Kiang JG, Gist ID, and Tsokos GC. 17-Estradiol-induced increases in glucose-regulated proteins protect human breast cancer T47-D cells from thermal injury. Chin. J. Physiol. 40:213-219, 1997.
52. Kiang JG, Ding XZ, and McClain DE. Overexpression of HSP-70 attenuates increases in [Ca2+]i and protects human epidermoid A-431 cells after chemical hypoxia. Toxicol. Appl. Pharmacol. 149:185-194, 1998.
53. Ding XZ, Tsokos GC, and Kiang JG. Overexpression of HSP-70 inhibits the phosphorylation of HSF1 by activating protein phosphatase and inhibiting protein kinase C activity. FASEB. J. 12:451-459, 1998.
54. Kiang JG, Gist ID, and Tsokos GC. Cytoprotection and regulation of heat shock proteins induced by heat shock in human breast cancer T47-D cells: role of [Ca2+]i and protein kinases. FASEB J. 12: 1571-1579, 1998.
55. Kiang JG and Tsokos GC. Heat shock protein 70 kD family: Molecular Biology, Biochemistry, and Physiology. Pharmacol.Ther. 80:183-201, 1998.
56. Kiang JG, Ding XZ, Gist ID, and Tsokos GC. Corticotropin-releasing factor increases phosphotyrosine of phospholipase C- at tyrosine residues via its receptor 2 in human epidermoid A-431 cells. Eur. J. Pharmacol. 363:203-210, 1998.
57. Goldhill JM, Stojadinovic A, KiangJG, Smallridge RC, and Shea-Donohue T. Hyperthermia prevents functional, histological and biochemical abnormalities induced during ileitis. Neurogastroenterol. Mot. 11:69-76, 1999.
58. Kiang JG, Gist ID, and Tsokos GC. Biochemical requirement of heat shock protein 72 kD expression in human breast cancer MCF-7 cells. Mol. Cell. Biochem.199: 179-188, 1999.
59. Wang XD, Kiang JG, Scheibel LW, and Smallridge RC. Phospholipase C activation by Na+/Ca2+ exchange is essential for monensin-induced Ca2+ influx and arachidonic release in FRTL-5 thyroid cells. J. Investig. Med., 47:388-396, 1999.
60. Kiang JG and McClain DE. N-nitro-L-arginine decreases resting cytosolic [Ca2+] and enhances heat stress-induced increase in cytosolic [Ca2+] in human colon carcinoma T84 cells. Chin. J. Physiol. 42: 153-160, 1999.
61. Smallridge RC, Gist ID, Tsokos GC, and Kiang JG. Characterization of distinct heat shock and thapsigargin-induced cytoprotective proteins in FRTL-5 cells. Thyroid, 9: 1041-1047, 1999.
62. Kiang JG, Gist ID, and Tsokos GC. Heat shock induces expression of heat shock protein 72 kD and 90 kD in human breast cancer MDA-231 cells. Mol. Cell. Biochem. 204: 169-178, 2000.
63. Kiang JC and Lu PY. Biological effects of qigong and an overview of research design and methodology. Proceedings: The Science and Spirituality of Healing, 1: 99-121, 2000.
64. Kiang JG, Kiang SC, Juang Y-T, and Tsokos GC. Nω-nitro-L-arginine inhibits the inducible heat shock protein 70 kDa via Ca2+, PKC, and PKA. Am. J. Physiol. 282:G415-G423, 2002.
65. Kiang JG, Marotta D, Wirkus M, Wirkus M, and Jonas WB. External bioenergy increases intracellular free calcium concentrations and reduces cellular response to heat stress. J. Investig. Med., 50: 38-45, 2002.
66. Fleming SD, Starnes BW, Kiang JG, Stojadinovic A, Tsokos GC, and Shea-Donohue T. Heat stress protection against mesenteric ischemia/reperfusion-induced alteration in intestinal mucosa in rats. J. Appl. Physiol. 92:2600-2607, 2002.
67. Kiang JG. Genistein inhibits herbimycin A-induced inducible heat shock protein 70 kDa. Mol Cell Biochem, 245:191-199, 2003.
68. Kiang JG, McClain DE, Warke VG, Krishnan S, and Tsokos GC. Constitutive NO synthase regulates the Na+/Ca2+ exchanger in human Jurkat T cells: role of [Ca2+]i and tyrosine phosphorylation. J. Cellular Biochem., 89:1030-1043, 2003.
69. Kiang JG, Warke VG, and Tsokos GC. NaCN-induced chemical hypoxia is associated with altered gene expression. Mol Cell Biochem 254:211-216, 2003.
70. Kiang JG, Bowman DP, Wu BW, Hampton N, Kiang AG, Zhao B, Juang Y-T, Atkins JL, and Tsokos GC. Geldanmaycin inhibits hemorrhage-induced increases in caspase-3 activity, KLF6, and iNOS expression in unresuscitated organs of mice: Role of inducible HSP-70. J Appl Phsiol 97:564-569, 2004.
71. Kiang JG, Bowman PD, Zhao B, Atkins JL, and Tsokos GC. Heat shock protein-70 inducers and iNOS inhibitors as therapeutics to ameliorate hemorrhagic shock. NATO-HFM-109-P28:1-11, 2004.
72. Fleming SD, Kiang JG, and Tsokos GC. Targeting complement in treatment of ischemia/reperfusion-induced injury. NATO-HFM-109-P24:1-13, 2004.
73. Bowman PD, Zhao B, Bynum JA, Sondeen JL, Kiang JG, Dubick MA, and Atkins JL. Application of gene expression analysis with microarrays and proteinomics to the problem of hemorrhagic shock and resuscitation. NATO-HFM-109-P29:1-15, 2004.
74. Kiang JG. Inducible heat shock protein 70 kD and inducible nitric oxide synthase in hemorrhage/resuscitation-induced injury. Cell Res 14:450-459, 2004.
75. Kiang JG, Ives JH, and Jonas WB. External bioenergy-induced increases in intracellular free calcium concentrations are mediated by the Na+/Ca2+ exchanger and L-type calcium channel. Mol Cell Biochem 271:51-59, 2005.
76. Kiang JG. Lu X, Tabaku LS, Bentley TB, Atkins JL, and Tsokos GC. Resuscitation with lactated Ringers solution limits the expression of molecular events associated with lung injury after hemorrhage. J Appl Physiol 98:550-556, 2005.
77. Krishnan S, Kiang JG, Fisher CU, Nambiar MP, Nguyen HT, Kyttaris VC, Chowdhury B, Rus V, Tsokos GC. Increased caspase-3 expression and activity contributes to reduced CD3 expression in Systemic Lupus Erythematosus T cells. J Immunol 175:3417-3423, 2005.
78. Kiang JG, Bowman DP, Lu X, Li Yansong, Ding XZ, Zhao B, Juang YT, Atkins JL, Tsokos GC. Geldanmaycin treatment prevents hemorrhage-induced ATP loss in mouse organs by overexpressing HSP-70 and activating pyruvate dehydrogenase. Am J Physiol 291:G117-G127, 2006.
79. Tsen KT, Tsen SWD, Kiang JG. Lycopene is more potent than bata carotene in the neutralization of singlet oxygen: role of energy transfer probed by ultrafast Raman spectroscopy. J Biomed Optics 11:064025 (6 pages), 2006.
80. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN: Dependence on the injected carrier density. App Physics Lett 89:11211 (3 pages), 2006.
81. Tsen KT, Kiang JG, Ferry DK, Kochelap VA, Komirenko SM, Kim KW, Morkoc H. Subpicosecond Raman studies of electric-field-induced optical phonon instability in an In0.53Ga0.47As-based semiconductor nanostructure. J Phys: Condens Matter 18:7961-7974, 2006.
82. Kiang JG, Tsen KT. Biology of hypoxia. Chin J Physiol 49:223-233, 2006.
83. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Observation of the low frequency vibrational modes of bacteriophage M13 in water by Raman spectroscopy. Virology J 3:79 (11 pages), 2006.
84. Tsen KT, Dykeman E, Sankey OF, Lin N-T, Tsen S-WD, Kiang JG. Raman scattering studies of the low frequency vibrational modes of bacteriophage M13 in water. Nanotecnology 17:5474-5479, 2006.
85. Tsen KT, Kiang JG, Ferry DK, and Morkoc H. Subpicosecond time-resolved Raman studies of field-induced transient transport in an -based p-i-n semiconductor nanostructure. App Physics Lett, 89: 262101 (3 pages), 2006.
86. Tsen KT, Kiang JG, and Ferry DK. Subpicosecond transient Raman scattering studies of field-induced electron transport in an -based p-i-n nanostructure: Direct observation of the effects of electron momentum randomization. J Phys: Condens Matter 18:L585-L592, 2006.
87. Kiang JG, Peckham RM, Duke LE, Chaudry IH, Tsokos GC. Androstenediol inhibits trauma-hemorrhage-induced increase in caspase-3 by downregulating inducible nitric oxide synthase pathway. J App Physiol 102: 933-941, 2007.
88. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Probing the low frequency vibrational modes of viruses with Raman scattering -- bacteriophage M13 in water. J Biomed Optics. 12: 024009 (6 pages), 2007.
89. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN. Proc of SPIE 6473: 64730Q-1 – 64730Q-12, 2007.
90. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Studies of longitudinal optical phonons in GaN by sybpicosecond time-resolved Raman Spectroscopy. Proc of SPIE 6471: 64710X-1 – 64710X-10, 2007.
91. Kiang JG, Bowman DP, Lu X, Li Y, Wu BW, Loh HH, Tsen KT, Tsokos GC. Geldanmaycin treatment inhibits hemorrhage-induced increases in caspase-3 activity: Role of inducible nitric oxide synthase. J App Physiol 103: 1045-1055, 2007.
92. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Direct measurements of the lifetimes of longitudinal optical phonon modes and their dynamics in InN. App Physics Lett 90: 152107 (3 pages), 2007.
93. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Subpicosecond time-resolved Raman studies of electron-longitudinal optical phonon interactions in InN. App Physics Lett 90: 172108 (3 pages), 2007.
94. Tsen KT, Kiang JG, Ferry DK, Lu H, Schaff WJ, Lin HW, Gwo S. Electron-density dependence of longitudinal-optical phonon lifetime in InN studied by subpicosecond time-resolved Raman spectroscopy. J Phy Condens Matter 19: 236219 (8 pages), 2007.
95. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by coherent excitations with low power visible femtosecond laser. Virology J 4:50 (6 pages), 2007.
96. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses with a very low power visible femtosecond laser. J Physics: Condens Matter 19:322102 (9 pages), 2007.
97. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by laser-driven coherent excitations via impulsive stimulated Raman scattering process. J Biomed Optics 12:064030 (6 pages), 2007.
98. Tsen KT, TsenS-W D, Sankey OF, Kiang JG. Selective inactivation of microorganisms by near-IR femosecond laser pulses. J Phy Condens Matter 19: 472201 (7 pages), 2007.
99. Kiang JG, Krishnan S, Lu X, Li Y. Inhibition of inducible nitric oxide synthase protects human T cells from hypoxia-induced injury. Mol Pharmacol 73:738-747, 2008.
100. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kiang JG. Selective inactivation of human immunodeficiency virus with subpicosecond near-infrared laser pulses. J Phys Condens matter 20:25220 (4 pages), 2008.
101. Atkins JL, Hammamiech R, Jett M, Gorbounov NV, Asher LV, Kiang JG. α-Defensin-4 and asymmetric dimethyl arginine (ADMA) increase in mesenteric lymph after hemorrhage in anesthetized rats. Shock 30: 411-146, 2008.
102. Tsen KT, Tsen S-W D, Chang C-L, Hung C-F, Wu T-C, Ramakrishna K, Mossman K, Kiang JG. Inactivation of viruses with a femtosecond laser via impulsive stimulated Raman scattering. In: Optical Interactions with Tissue and Cells XIX (edited by Steven L. Jacques, William P. Roach, Robert J. Thomas), Proc. of SPIE 6854: 68540N1-6854N10, 2008.
103. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Dynamics of LO phonons in InN studied by subpicosecond time-resolved Raman spectroscopy. In: Ultrafast Phenomena in Semiconductors and Nanostructure Materials XII (edited by J.J. Song, K.T. Tsen, M. Betz and A. Elezzabi), Proc. of SPIE Vol. 6892: 689206 (12 pages), 2008.
104. Kiang JG, Kiang SC, Bowman PD. 17-DMAG inhibits hemorrhage-induced injury in small intestine and lung by inactivating caspase-3. International Proceedings of International Shock Congress K628C0171:23-27, 2008.
105. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kibler K, Jacob B, Kiang JG. Selective inactivation of human immunodeficiency virus with an ultrashort pulsed laser. Proc. of SPIE 7175: 717510-1 – 717510-8, 2009.
106. Kiang JG, Smith JA, and Agravante NG. Geldanamycin analog 17-DMAG inhibits iNOS and caspases in gamma irradiated human T cells. Radiat Res 172: 321-330, 2009.
107. Gorbunov NV, Kiang JG. Up-regulation of Autophagy in the Small Intestine Paneth Cell in Response to Total-Body γ-Irradiation. J Pathol 219: 242-252, 2009.
108. Jiao W, Kiang JG, Cary L, Elliott TB, Pellmar TC, Ledney GD. COX-2 inhibitors are contraindicated for therapy of combined injury. Radiat Res 172: 686-697, 2009.
109. Tsen KT, Tsen S-WD, Fu Q, Lindsay SM, Kibler K, Jacobs B, Wu TC, Karanam B, Jagu S, Roden RBS, Hung C-F, Sankey OF, Ramakrishna B, Kiang JG. Photonic approach to the selective inactivation of viruses with a near-infrared subpicosecond fiber laser. J Biomed Opt 14: 064042 (10 pages), 2009.
110. Kiang JG, Jiao W, Cary L, Mog SR, Elliott TB, Pellmar TC, Ledney GD. Wound trauma increases radiation-induced mortality by increasing iNOS, cytokine concentrations, and bacterial infections. Radiate Res 173: 319-332, 2010.
111. Kiang JG, Garrison BR, Gorbunov NV. Radiation combined injury: DNA damage, apoptosis, and autophagy. Adapt Med 2: 1-10, 2010. doi: 10.4247/AM.2010.ABA004.
112. Daly MJ, Gaidamakova EK, Matrosova VY, Kiang JG, Fukumoto R, Wehr NB, Viteri G, Berlett BS, Levine RL. Small molecule proteome-shield in Deinococcus radiodurans. PLoS One 5(9): e12570 (15 pages), 2010.
113. Gorbunov NV and Kiang JG. Activation of IL-1β pathway and augmentation of Paneth cell α-defensin-4 in small intestine following total-body γ-irradiation. Intl J Immunopathol Pharmacol 23: 1111-1123, 2010.
114. Kiang JG, Smith JA, Agravante NG, Gorbunov NV. Geldanamycin analog 17-DMAG has radioprotective activity in mice. Radiat Res, in review.
115. Fukumoto R, Kiang JG. Geldanamycin analog 17-DMAG limits apoptosis in human peripheral blood cells by inhibition of p53 activation and its interaction with heat shock protein 90 kDa after ionizing radiation. Radiat Res 176: 333-345, 2011.
116. Kiang JG, Agravante NG, Smith JT, Bowman PD. 17-DMAG increases Bcl-2 and inhibits hemorrhage-induced increases in iNOS activation, caspase-3 activity and TNF-a. Cell & Bioscience 1: 21 (10 pages), 2011.
117. Tsen KT, Tsen SWD, Fu Q, Lindsay SM, Li Z, Yan H, Cope S, Vaiana S, Kiang JG. Studies of inactivation of encephalomyocaditis virus, M13 bacteriophage and Salmomella typhimurium by using a visible femtosecond laser irradiation: insight into the possible inactivation mechanisms. J Biomed Optics 16: 078003 (11 pages), 2011.
118. Whitnall MH, Cary LH, Moroni M, Ngudiankama BF, Landauer MR, Singh VK, Ghosh SP, Kulkarni S, Miller AC, Kiang JG, Srinivasan V, Xiao M. United States Armed Forces Radiobiology Research Institute countermeasures program and related policy questions. Proceedings,Hiroshima University, 2012.
119. Kiang JG, Garrison BR, Burns TM, Zhai M, Dews IC, Ney PH, Fukumoto R, Cary LH, Elliott TB, Ledney GD. Wound trauma alters ionizing radiation dose assessment. Cell Bioscience 2: 20 (12 pages), 2012.
120. Tsen S-W D, Wu TC, Kiang JG, Tsen KT. Prospects for a novel ultrashort pulsed laser technology for pathogen inactivation. J Biomed Sci 19: 62 (11 pages), 2012.
121. Kiang JG. Overview of biological effects of irradiation combined injury. NATO-HFM-223-P5:1-18, 2012.
122. Fukumoto R, Cary LH, Gorbunov NV, Elliott TB, Kiang JG. Ciprofloxacin modulates cytokine profiles, accelerates bone marrow recovery and mitigates ileum injury after radiation combined with wound trauma. PLoS One 8: e58389 (11 pages), 2013. doi: 10.1371/journal.pone.0058389. PMID: 23520506
123. Gorbunov NV, Garrison BR, McDaniel DP, Zhai M, Liao1 P-J, Nurmemet N, Kiang JG. Adaptive redox response of mesenchymal stromal cells to stimulation with lipopolysaccharide inflammagen: mechanisms of remodeling of tissue barriers in sepsis. Oxid Med Cell Longev 2013: 186795 (16 pages), 2013. doi: 10.1155/2013/186795. PMID: 23710283
124. Lu X, Nurmemet D, Bolduc DL, Elliott TB, Kiang JG. Radioprotective effects of oral 17-DMAG in mice: Bone marrow and small intestine. Cell Bioscience 3: 36 (16 pages), 2013. doi: 10.1186/2045-3701-3-36. PMID: 24499553
125. Kiang JG, Ledney GD. Skin injuries reduce survival and modulate corticosterone, C-reactive protein, complement component 3, IgM, and prostaglandin E2 after whole-body reactor-produced mixed field (n + γ-photons) irradiation. Oxid Med Cell Longev, 2013: 821541 (10 pages), 2013. doi: 10.1155/2013/821541. PMID: 24175013
126. Kiang JG, Garrison BR, Smith JT, Fukumoto R. Ciprofloxacin as a potential radio-sensitizer to tumor cells and a radioprotectant for normal cells: Differential effects on -H2AX formation, p53 phosphorylation, Bcl-2 production, and cell death. Cell Mol Biochem 393: 133-143, 2014. doi: 10.1007/s11010-014-2053-z. PMID: 24802382
127. Kiang JG, Fukumoto R. Ciprofloxacin increases survival after ionizing irradiation combined injury: gamma-H2AX formation, cytokine/chemokine, and red blood cells. Health Physics 106: 720-726, 2014. doi: 10.1097/HP.0000000000000108. PMID: 24776905
128. Fukumoto R, Burns TM, Kiang JG. Ciprofloxacin Enhances Stress Erythropoiesis in Spleen and Increases Survival after Whole-Body Irradiation Combined with Skin-Wound Trauma, PLoS One 9(2): e90448, 2014. doi: 10.1371/journal.pone.0090448. PMID: 24587369
129. Kiang JG, Zhai M, Liao P-J, Bolduc DL, Elliott TB, Gorbunov NV. Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn. Oxid Med Cell Longev 2014: 481392 (10 pages), 2014. doi: 10.1155/2014/481392. PMID: 24738019
130. Kiang JG, Zhai M, Liao P-J, Elliott TB, Gorbunov NV. Ghrelin therapy improves survival after whole-body ionizing irradiation combined with wound or burn: Amelioration of leukocytopenia, thrombopenia, splenomegaly, and bone marrow injury. Oxid Med Cell Longev 2014: 215858, 2014. doi: 10.1155/2014/215858. PMID: 25374650
131. Gorbunov NV, Elliott TB, McDaniel DP, Zhai M, Liao P-J, Kiang JG. Mitophagy and mitochondrial remodeling in mouse mesenchymal stromal cells following a challenge with Staphylococcus epidermidis. J Cell Mol Med 19:1133-1150, 2015. doi: 10.1111/jcmm.12518. PMID: 25721260
132. Kiang JG, Gorbunov NV. Bone marrow mesenchymal stem cells increases survival after ionizing irradiation combined with wound trauma: Characterization and therapy. J Cell Sci Ther 5:190 (8 pages), 2014. doi: 10.4172/2157-7013.1000190
133. Elliott TB, Bolduc DL, Ledney GD, Kiang JG, Fatanmi OO, Wise S, Romaine PLP, Newman VL, Singh VK. Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in mice exposed to radiation and combined injury. Int J Radiat Biol 91(9):690-702, 2015. doi: 10.3109/09553002.2015.1054526. PMID: 25994812
134. Swift JM, Smith JT, Kiang JG. Ciprofloxacin therapy mitigates ATP loss after irradiation combined with wound trauma: Preservation of pyruvate dehydrogenase and inhibition of pyruvate dehydrogenase kinase 1. Radiat Res 183: 684-692, 2015. PMID: 26010714
135. Swift JM, Smith JT, Kiang JG. Hemorrhage Trauma Increases Radiation-Induced Trabecular
Bone Loss and Marrow Cell Depletion in Mice. Radiat Res 183: 578-583, 2015. doi: 10.1667/RR13960.1 PMID: 25897554
136. Swift JM, Swift SN, Smith JT, Kiang JG, Allen MR. Skin wound trauma, following high-dose radiation exposure, amplifies and prolongs skeletal tissue loss. Bone 81: 487-494, 2015. doi: 10.1016/j.bone.2015.08.022 PMID: 26335157
137. Islam A, Bolduc DL, Zhai M, Kiang JG, Swift JM. Daily Captopril Dosing Increases Survival after Whole-Body Ionizing Irradiation but Decreases Survival after in combination with Combined Burn Trauma in Mice. Radiat Res 184:273-279, 2015. doi: 10.1667/RR14113.1. PMID: 26305295
138. Kiang JG, Smith JT, Anderson MN, Swift JM, Gupta P, Balakathiresan N, Maheshwari RK. Hemorrhage exacerbates radiation effects on survival, leukocytopenia, thrombopenia, erythropenia, bone marrow cell depletion and hematopoiesis, and inflammation-associated microRNAs expression in kidney. PLoS ONE 10:e0139271, 2015. doi: 10.1371/journal.pone.0139271. PMID: 26422254
139. Klionsky DJ…Kiang JG…Zughaler SM. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12: 1-222, 2016. PMID: 26799652
140. Kiang JG. Adult mesenchymal stem cells and radiation injury. Health Phys 111:198-203, 2016. doi: 10.1097/HP.0000000000000459. PMID: 27356065
141. Gupta P, Gayen M, Smith JT, Matrosova VY, Gaidamakova EK, Daly MJ, Kiang JG, Maheshwari RK. MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation. PLoS One 11: e0160575, 2016. doi: 10.1371/journal.pone.0160575. PMID: 27500529
142. Kiang JG. Exacerbation of mild hypoxia on acute radiation syndrome and subsequent mortality. Adaptive Med 9(1): 28-33, 2017. doi: 10.4247/AM.2017.ABG170
143. Kiang JG, Zhai M, Liao P.-J., Ho C, Gorbunov NV, Elliott TB. Thrombopoietin receptor agonist mitigate hematopoietic acute radiation syndrome and improves survival after whole-body ionizing irradiation followed by wound trauma. Mediators of Inflammation 2017:7582079, 2017. doi: 10.1155/2017/7582079 PMID: 28408792
144. Kiang JG, Zhai M, Bolduc DL, Smith JT, Anderson MN, Ho C, Lin B, Jiang S. Combined therapy of pegylated-G-CSF and Alx4100TPO improves survival and mitigate acute radiation syndrome after whole-body ionizing irradiation alone and followed by wound trauma. Radiat Res 188:476-490, 2017. doi: 10.1667/RR14647.1 PMID: 28850300
145. Kiang JG, Smith JT, Anderson MN, Elliott TB, Gupta P, Balakathiresan N, Maheshwari RK, Knollmann-Ritschel B. Hemorrhage enhances cytokine, complement component 3, and caspase-3, and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury. PLoS ONE 12(9):e0184393, 2017. doi: 10.1371/journal.pone.0184393.PMID: 28934227
146. Gorbunov NV, Kiang JG. Ghrelin therapy decreases incidents of intracranial hemorrhage in mice after whole-body ionizing irradiation combined with burn trauma. Int J Mol Sci 18(8). pii: E1693, 2017. doi: 10.3390/ijms18081693. PMID: 28771181
147. Kiang JG, Smith JT, Hegge SR, Ossetrova N. Circulating cytokine/chemokine concentrations respond to ionizing radiation doses but not radiation dose rates: granulocyte-colony stimulating factor and interleukin-18. Radiat Res, in press, 2018.
148. Kiang JG, Anderson MN, Smith JT. Ghrelin therapy sustains granulocyte colony-stimulating factor and keratinocyte factor to mitigate hematopoietic syndrome and spleen after whole-body ionizing irradiation combined with wound. Cell Biosci 8:27, 2018. doi: 10.1186/s13578-018-0225-3.
149. Li X, Cui W, Hull L, Smith JT, Kiang JG, Xiao M. Effects of low-moderate doses of γ-radiation on mouse hematopoietic and immune system. Radiat Res, in review, 2018.
E-Book (1)
1. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. Cell Biology Research Progress, Nova Science Publishers, INC. Hauppauge, NY. ISBN: 978-1-62417-374-5 http://www.novapublishers.com, 2012.
Book chapters (10)
1. Yan X, Lu PY, and Kiang JG. Qigong: basic science studies in Biology. In: Healing, Intention, and Energy medicine Science, Research Methods and Clinical Implications. (Eds. WB Jonas and C Crawford) Churchill Livingstone, London, UK pp. 103-119, 2003.
2. Kiang JG and McClain DE. Heat stress. In: Combat Medicine Basic and Clinical Research in Military, Trauma, and Emergency Medicine (Eds. GC Tsokos and JL Atkins), Humana Press, New Jersey, pp. 83-101, 2003.
3. Kiang JG. Human bioenergy effects at the cellular and molecular level. In: Life and Mind In Search of Physical Basis (ed. S. Savva), Trafford Publishing, Victoria BC, Canada, pp. 117-137, 2007.
4. Tsen KT, Tsen SWD, Dykeman EC, Sankey OF, Kiang JG. Inactivation of viruses with femtosecond laser pulses. In: Contemporary Trends in Bacteriophage research (Ed: Horace T. Adams), Nova Science Publishers, NY, ISBN: 978-1-60692-181-4, pp. 151-177, 2009.
5. Kumar KS, Kiang JG, Whitnall MH, Hauer-Jensen M. Perspectives in radiological and nuclear countermeasures. In: Textbook of Military Medicine, pages 239-266, 2012.
6. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. In: Autophagy: Principles, Regulation and Roles in Disease (ed: Gorbunov NV), Nova Science Pulbishers, INC. Hauppauge, NY. 2012.
7. Gorbunov NV, Garrison BR, Zhai M, McDaniel DP, Ledney GD, Elliott TB, Kiang JG. Autophagy-mediated defense response of mouse mesenchymal stromal cells (MSCs) to challenge with Escherichia coli. In: Protein Interaction / Book 1; ISBN 979-953-307-577-7. Eds.: Cai J and Wang H. InTech Open Access Publisher; www.intechweb.org. pp. 23-44, 2012.
8. Kiang JG, Fukumoto R, Gorbunov NV. Lipid peroxidation after ionizing irradiation leads to apoptosis and autophagy. In: Lipid Peroxidation; ISBN 980-953-307-143-0. Eds.: Angel Catala, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp.261-278, 2012.
9. Gorbunov NV, Elliott TB, McDaniel DP, Lund K, Liao PJ, Zhai M, Kiang JG. Up-regulation of autophagy defense mechanisms in mouse mesenchymal stromal cells in response to ionizing irradiation followed by bacterial challenge. In: Autophagy, ISBN 980-953-307-971-9. Ed: Yannick Bailly, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp. 331-350, 2013.
10. Kiang JG. Characterization and therapeutic uses of adult mesenchymal stem cells. In: Stem Cell Toxicity and Medicine (ed. S.C. Sahu). Wiley & Sons, West Sussex, pp. 288-301, 2016.
Dr. Kiang serves in editorial boards of several scientific journals, NIH and VA study sections, and USU committees. She worked in Water Reed Army Institute of Research from 1989 to 2006 before joining AFRRI.
Dr. Kiang is involved in studies showing corticotrophin-releasing factor and heat shock proteins are capable of protecting against edema/inflammation and hypoxia injury, respectively. She demonstrates that overexpression of inducible form of heat shock protein 70 kDa induced by sublethal heat stress, chemical stimulation, or the gene transfer produces thermotolerance and cross-tolerance that may be related to an inhibition of changes in intracellular calcium concentrations and expression of stress-related genes and proteins such as inducible nitric oxide synthase and p38-MAPK. She has found 17-DMAG, mesenchymal stem cells, G-CSF, ghrelin, or ciprofloxacin that can make cells endure much better under circumstances of low oxygen, a way to treat heat stroke, ischemia, hemorrhage, cancer, heart attack, stroke, or ionizing radiation injury.
Dr. Kiang had made four major contributions in her research career (journal references to work are noted).
Dr. Kiang is the first to demonstrate that treatment with corticotrophin-releasing factor (CRF) inhibits neurogenic and thermally-induced protein extravasation in rats (9-14). She also found that urotensin I and sauvagine (members of the CRF superfamily) possess the same properties as CRF but with greater potency (15). She holds a patent resulting from this work. She has provided evidence that CRF and its analogs increase intracellular Ca2+ concentrations in vitro (33, 36, 50), which are correlated with capacity of these neuropeptides to inhibit thermally-induced edema (50). CRF exerts its action on CRF type 2 receptors to activate enzymes such as tyrosine kinases, phospholipase 1 and 2 to lead to a result of increases in intracellular Ca2+ concentrations (56). A patent is resulted.
Dr. Kiang’s second major contribution is that she performed extensive research to establish the effect of heat shock on components of signal transduction pathways, such as H+, Ca2+, Na+, cAMP, inositol 1,4,5-trisphosphate, and heat shock proteins in cultured cells. Her findings in this area are wide-ranging and have extended knowledge in the heat shock field (18, 19, 22, 25, 29, 40-42, 44, 46-48, 51-55, 57, 58, 60-62). Her findings provide insight to unfold the mechanisms of tolerance and cross-tolerance (64, 67). Heat shock protein 70 kDa plays a very important role in cell survival – a fine-line before occurrence of apoptosis.
Dr. Kiang’s third major contribution is that she has shown heat shock protein 70 kDa (HSP-70i) can protect the rat ileum from the ischemia/reperfusion injury (37, 66), ricin injury (47), during ileitis (57), and the mouse jejunum, lung, heart, and kidney from the hemorrhagic shock (70). She has also shown that down-regulation of inducible nitric oxide synthase inhibits the activity of caspase-3, an apoptotic protease, and overexpression of HSP-70i prevents ATP loss resulted from hemorrhage (78, 87, 91, 99, 104) or radiation-injury (106-108, 110-114). The work has resulted in a provisional patent.
Dr. Kiang’s fourth major contribution is that she has characterized radiation combined injury (110, 111, 115, 120) shown that ciprofloxacin (122, 126-128, 134), ghrelin (130, 146), and bone marrow mesenchymal stem cells (132, 140) can combat radiation injury combined with skin-wound injury. The research work is ongoing. Meanwhile, she established a new combined injury model of radiation with hemorrhage (135, 138, 142, 145) that brought her the 2016 AFRRI Research Award.
Bubliography
Peer-reviewed publications (149)
1. Kiang JG, Dewey WL, and Wei ET. Tolerance to morphine bradycardia in the rat. J. Pharmacol Exp. Ther. 226:187 192, 1983.
2. Kiang JG and Wei ET. Inhibition of an opiate-induced vagal reflex in rats by naloxone, SMS 201 995 and ICI 154, 129. Regulatory Peptides 6:255 262, 1983.
3. Dashwood MR, Kiang JG, and Wei ET. An etorphine-evoked reflex in rats is inhibited by naloxone, N-methylnaloxone, and SMS 201 995. Arch. Int. Pharmacodyn. Ther. 266:77 82, 1983.
4. Kiang JG and Wei ET. Sensitivity to morphine-evoked bradycardia in rats is modified by dynorphin (1 13), (Leu)enkephalin and (Met)enkephalin. J. Pharmacol. Exp. Ther. 229:469 473, 1984.
5. Kiang JG and Wei ET. Peripheral opioid receptors influencing heart rate in rats: evidence for endogenous tolerance. Regulatory Peptides 8:297 303, 1984.
6. Tang J, Webber RJ, Chang D, Chang JK, Kiang JG, and Wei ET. Depressor and natriuretic activities of several atrial peptides. Regulatory Peptides 9:543 549, 1984.
7. Wei ET and Kiang JG. Peripheral opioid receptors influencing heart rate in rats. In: Opioid Peptides in the Periphery. (Eds, F. Fraioli, A. Isidori and M. Mazzetti) Developments in Neuroscience 18:95 101, 1984, Amsterdam, Elsevier.
8. Kiang JG and Wei ET. CRF-evoked bradycardia in urethane-anesthetized rats is blocked by naloxone. Peptides 6:409 413, 1985.
9. Kiang JG and Wei ET. CRF: an inhibitor of neurogenic plasma extravasation produced by saphenous nerve stimulation. Eur. J. Pharmacol. 114:111 112, 1985.
10. Wei ET, Kiang JG, Buchan P, and Smith T. Corticotropin-releasing factor (CRF) inhibits neurogenic plasma extravasation in the rat paw. J. Pharmacol. Exp. Ther. 238:783 787, 1986.
11. Kiang JG and Wei ET. Corticotropin-releasing factor (CRF) inhibits thermal injury. J. Pharmacol. Exp. Ther. 243:517- 520, 1987.
12. Wei ET and Kiang JG. Inhibition of protein exudation from the trachea by corticotropin-releasing factor. Eur. J. Pharmacol. 140:63-67, 1987.
13. Wei ET, Kiang JG, and Tien JQ. Anti-inflammatory activity of corticotropin-releasing factor: I. Efficacy studies. Proc. West. Pharmacol. Soc. 30:59 62, 1987.
14. Kiang JG, Poree L, and Wei ET. Anti-inflammatory activity of corticotropin-releasing factor: II. Mechanisms of action. Proc. West. Pharmacol. Soc. 30:63 65, 1987.
15. Wei ET and Kiang JG. Peptides of the corticoliberin superfamily attenuate thermal and neurogenic inflammation in rat paw skin. Eur. J. Pharmacol. 168:81 86, 1989.
16. Kiang JG and Colden-Stanfield M. Morphine induces an intracellular alkalinization in bovine aortic endothelial cells (BAECs), In: International Narcotic Research Conference (INRC) '89. (Eds. R. Quirion, K. Jhamandas and C. Gianoulakis) Alan Liss Press, N.Y., Prog. Clin. Biol. Res. 328:137 140, 1989.
17. Wei ET, Wong JC, and Kiang JG. Decreased inflammatory responsiveness of hypophysectomized rats to heat is reversed by a CRF antagonist. Regulatory Peptides 27:317 323, 1990.
18. Kiang JG, McKinney LC, and Gallin EK. Heat induces an intracellular acidification in human A 431 cells: role of Na+/H+ exchanger and metabolism. Am. J. Physiol., 259(Cell Physiol. 28):C727-C737, 1990.
19. Kiang JG, Wu YY, and Lin M. Hyperthermia elevates cAMP levels in human epidermoid A 431 cells. Biochem. J. 276:683 689, 1991.
20. Kiang JG. Effect of intracellular pH on cytosolic free [Ca2+]i in A-431 cells. Eur. J. Pharmacol. 207(Molecular Pharmacol. Section):287-296, 1991.
21. Lin W-W, Kiang JG, and Chuang D-M. Pharmacological characterization of endothelin-stimulated phosphoinositides breakdown and cytosolic Ca2+ rise in C6 rat glioma cells. J. Neurosci., 12:1077 1085, 1992.
22. Kiang JG, Koenig ML, and Smallridge RC. Heat shock increases cytosolic free Ca2+ concentration via the Na+/Ca2+ exchange in human epidermoid A 431 cells. Am. J. Physiol. 263(Cell Physiol. 32):C30-38, 1992.
23. Smallridge RC, Gist ID, and Kiang JG. Na+-H+ antiport and monensin effects on cytosolic pH and iodide transport in FRTL 5 rat thyroid cells. Am. J. Physiol. 262(Endocrinol. Metab.) 25:E834-E839, 1992.
24. Smallridge RC, Kiang JG, Gist ID, Fein HG, and Galloway R. U 72133 inhibits TRH-induced activities in GH3 cells. Endocrinol. 131:1883 1888, 1992.
25. Kiang JG and McClain DE. Effect of heat shock, Ca2+, and cAMP on inositol 1,4,5-trisphosphate in human epidermoid A 431 cells. Am. J. Physiol. 264 (Cell Physiol. 33):C1561-C1569, 1993.
26. Aloj SM, Liguoro D, Kiang JG, and Smallridge RC. Purinergic (P2) receptor -operated calcium entry into rat thyroid cells. Biophy. Biochim. Res. Comm. 195:1-7, 1993.
27. Kiang JG. Corticotropin-releasing factor increases cytosolic free calcium via receptor-mediated Ca2+ channels. Eur. J. Pharmacol. (Molecular Pharmacol. Section) 267:135-142, 1994.
28. Kiang JG and Smallridge RC. Sodium cyanide increases cytosolic free calcium: Evidence of activation of the reversed mode of Na+/Ca2+ exchanger and Ca2+ mobilization from inositol trisphosphate-insensitive pools. Toxicol. Appl. Pharmacol., 127:173-181, 1994.
29. Kiang JG, Carr FE, Burns MR, and McClain DE. HSP-72 synthesis is promoted by increase in [Ca2+]i or activation of G proteins but not pHi or cAMP. Am. J. Physiol. 267 (Cell Physiol. 36):C104-C114, 1994.
30. Tang T, Kiang JG, and Cox BM. Opioids acting through delta-receptors increase the intracellular free calcium concentration in the dorsal root ganglion neuroblastoma hybrid ND8-47 cells. J. Pharmacol. Exptl. Ther., 270:40-46, 1994.
31. Wang X, Kiang JG, and Smallridge RC. U-73122 inhibits increases in inositol trisphosphates and cytosolic free [Ca2+] induced by TSH in FRTL-5 cells. Bioph. Biochim. Acta, 1223:101-106, 1994.
32. Poola I and Kiang JG. The estrogen inducible transferrin receptor-like membrane glycoprotein is related to stress regulated proteins. J. Biol. Chem. 269:1-8, 1994.
33. Kiang JG, Wang XD, and McClain DE. Corticotropin-releasing factor increases protein kinase C activity by elevating isoforms and at the membrane. Chin J. Physiol. 37:105-110, 1994.
34. Wang XD, Kiang JG, and Smallridge RC. Identification of protein kinase C and its multiple isoforms in Frtl-5 thyroid cells. Thyroid 5:137-140, 1995.
35. Tang T, Kiang JG, Cote T, and Cox BM. Opioid-induced increase [Ca2+]i in ND8-47 neuroblastoma X DRG hybrid cells is mediated through G protein-coupled delta opioid receptors and desensitized by chronic exposure to opioid. J. Neurochem. 65:1612-1621, 1995.
36. Kiang JG. Mystixin-7 and Mystixin-11 increase [Ca2+]i and inositol trisphosphates in human A-431 cells. Eur. J. Pharmacol. (Mol. Pharmacol. Section) 291:107-113, 1995.
37. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Heat shock protein 72 kD induction protects rat intestinal mucosa from ischemia/reperfusion injury. Gastroenterol. 109:505-515, 1995.
38. Tang T, Kiang JG, Cote T, and Cox BM. Antisense oligodeoxynucleotide to Gái2 protein á-subunit sequence inhibits an opioid-induced increase in intracellular free calcium in ND8-47 neuroblastoma x DRG hybrid cells. Mol. Pharmacol. 48:189-193, 1995.
39. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Rapid assay of HSF1 and HSF2 gene expression by reverse transcriptase PCR. Mol. Cell Biochem. 158: 48-51, 1996.
40. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Increases in HSF1 translocation and synthesis in human epidermoid A-431 cells: role of protein kinase C and [Ca2+]i. J. Investig. Med. 44:144-153, 1996.
41. Kiang JG, Ding XZ, and McClain DE. Thermotolerance attenuates heat-induced increases in [Ca2+]i and HSP-72 synthesis but not heat-induced intracellular acidification in human A-431 cells. J. Investig. Med. 44:189-192, 1996.
42. Kiang JG, Wang XD, Ding XZ, Gist I, and Smallridge RC. Heat shock inhibits the hypoxia-induced effects on iodide uptake and signal transduction and enhances cell survival in rat thyroid FRTL-5 cells. Thyroid, 6:475-483, 1996.
43. Wang XD, Kiang JG, Atwa MA, and Smallridge RC. Evidence for the involvement of protein kinase C isoforms in á-1 adrenergic activation of phospholipase A2 in Frtl-5 thyroid cells, J. Investig. Med. 44:566-574, 1996.
44. Kiang JG and Koenig ML. Characterization of intracellular calcium pools in thermotolerant and their desensitization in thermotolerant cells. J. Investig. Med. 44:352-361, 1996.
45. Kiang JG and Tsokos GC. Signal transduction and heat shock protein expression. J. Biomed. Sci. 3:379-388, 1996.
46. Ding XZ, Tsokos GC, Smallridge RC, and Kiang JG. Heat shock gene expression in HSP-70 and HSF1 gene-transfected human epidermoid A-431 cells. Mol. Cell. Biochem. 167:145-152, 1997.
47. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Induction of the heat shock response limits tissue injury during acute inflammation of the rat ileum. Critical Care Medicine 25:309-317, 1997.
48. Ding XZ, Tsokos GC, and Kiang JG. Heat shock factor 1 protein in heat shock factor 1 gene-transfected human epidermoid A-431 cells requires phosphorylation prior to inducing heat shock protein-70 production. J. Clin. Investig. 99:136-143, 1997.
49. Liossis S-N, Ding XZ, Kiang JG, and Tsokos GC. Overexpression of HSP70 offers thermoprotection but enhances the TCR/CD3- and Fas-induced apoptotic death in Jurkat T-cells. J. Immunol. 158:5668-5675, 1997.
50. Kiang JG. Corticotropin-releasing factor-like peptides increase cytosolic free calcium in human epidermoid A-431 cells. Eur. J. Pharmacol. (Molecular Pharmacology Section), 329:237-244, 1997.
51. Kiang JG, Gist ID, and Tsokos GC. 17-Estradiol-induced increases in glucose-regulated proteins protect human breast cancer T47-D cells from thermal injury. Chin. J. Physiol. 40:213-219, 1997.
52. Kiang JG, Ding XZ, and McClain DE. Overexpression of HSP-70 attenuates increases in [Ca2+]i and protects human epidermoid A-431 cells after chemical hypoxia. Toxicol. Appl. Pharmacol. 149:185-194, 1998.
53. Ding XZ, Tsokos GC, and Kiang JG. Overexpression of HSP-70 inhibits the phosphorylation of HSF1 by activating protein phosphatase and inhibiting protein kinase C activity. FASEB. J. 12:451-459, 1998.
54. Kiang JG, Gist ID, and Tsokos GC. Cytoprotection and regulation of heat shock proteins induced by heat shock in human breast cancer T47-D cells: role of [Ca2+]i and protein kinases. FASEB J. 12: 1571-1579, 1998.
55. Kiang JG and Tsokos GC. Heat shock protein 70 kD family: Molecular Biology, Biochemistry, and Physiology. Pharmacol.Ther. 80:183-201, 1998.
56. Kiang JG, Ding XZ, Gist ID, and Tsokos GC. Corticotropin-releasing factor increases phosphotyrosine of phospholipase C- at tyrosine residues via its receptor 2 in human epidermoid A-431 cells. Eur. J. Pharmacol. 363:203-210, 1998.
57. Goldhill JM, Stojadinovic A, KiangJG, Smallridge RC, and Shea-Donohue T. Hyperthermia prevents functional, histological and biochemical abnormalities induced during ileitis. Neurogastroenterol. Mot. 11:69-76, 1999.
58. Kiang JG, Gist ID, and Tsokos GC. Biochemical requirement of heat shock protein 72 kD expression in human breast cancer MCF-7 cells. Mol. Cell. Biochem.199: 179-188, 1999.
59. Wang XD, Kiang JG, Scheibel LW, and Smallridge RC. Phospholipase C activation by Na+/Ca2+ exchange is essential for monensin-induced Ca2+ influx and arachidonic release in FRTL-5 thyroid cells. J. Investig. Med., 47:388-396, 1999.
60. Kiang JG and McClain DE. N-nitro-L-arginine decreases resting cytosolic [Ca2+] and enhances heat stress-induced increase in cytosolic [Ca2+] in human colon carcinoma T84 cells. Chin. J. Physiol. 42: 153-160, 1999.
61. Smallridge RC, Gist ID, Tsokos GC, and Kiang JG. Characterization of distinct heat shock and thapsigargin-induced cytoprotective proteins in FRTL-5 cells. Thyroid, 9: 1041-1047, 1999.
62. Kiang JG, Gist ID, and Tsokos GC. Heat shock induces expression of heat shock protein 72 kD and 90 kD in human breast cancer MDA-231 cells. Mol. Cell. Biochem. 204: 169-178, 2000.
63. Kiang JC and Lu PY. Biological effects of qigong and an overview of research design and methodology. Proceedings: The Science and Spirituality of Healing, 1: 99-121, 2000.
64. Kiang JG, Kiang SC, Juang Y-T, and Tsokos GC. Nω-nitro-L-arginine inhibits the inducible heat shock protein 70 kDa via Ca2+, PKC, and PKA. Am. J. Physiol. 282:G415-G423, 2002.
65. Kiang JG, Marotta D, Wirkus M, Wirkus M, and Jonas WB. External bioenergy increases intracellular free calcium concentrations and reduces cellular response to heat stress. J. Investig. Med., 50: 38-45, 2002.
66. Fleming SD, Starnes BW, Kiang JG, Stojadinovic A, Tsokos GC, and Shea-Donohue T. Heat stress protection against mesenteric ischemia/reperfusion-induced alteration in intestinal mucosa in rats. J. Appl. Physiol. 92:2600-2607, 2002.
67. Kiang JG. Genistein inhibits herbimycin A-induced inducible heat shock protein 70 kDa. Mol Cell Biochem, 245:191-199, 2003.
68. Kiang JG, McClain DE, Warke VG, Krishnan S, and Tsokos GC. Constitutive NO synthase regulates the Na+/Ca2+ exchanger in human Jurkat T cells: role of [Ca2+]i and tyrosine phosphorylation. J. Cellular Biochem., 89:1030-1043, 2003.
69. Kiang JG, Warke VG, and Tsokos GC. NaCN-induced chemical hypoxia is associated with altered gene expression. Mol Cell Biochem 254:211-216, 2003.
70. Kiang JG, Bowman DP, Wu BW, Hampton N, Kiang AG, Zhao B, Juang Y-T, Atkins JL, and Tsokos GC. Geldanmaycin inhibits hemorrhage-induced increases in caspase-3 activity, KLF6, and iNOS expression in unresuscitated organs of mice: Role of inducible HSP-70. J Appl Phsiol 97:564-569, 2004.
71. Kiang JG, Bowman PD, Zhao B, Atkins JL, and Tsokos GC. Heat shock protein-70 inducers and iNOS inhibitors as therapeutics to ameliorate hemorrhagic shock. NATO-HFM-109-P28:1-11, 2004.
72. Fleming SD, Kiang JG, and Tsokos GC. Targeting complement in treatment of ischemia/reperfusion-induced injury. NATO-HFM-109-P24:1-13, 2004.
73. Bowman PD, Zhao B, Bynum JA, Sondeen JL, Kiang JG, Dubick MA, and Atkins JL. Application of gene expression analysis with microarrays and proteinomics to the problem of hemorrhagic shock and resuscitation. NATO-HFM-109-P29:1-15, 2004.
74. Kiang JG. Inducible heat shock protein 70 kD and inducible nitric oxide synthase in hemorrhage/resuscitation-induced injury. Cell Res 14:450-459, 2004.
75. Kiang JG, Ives JH, and Jonas WB. External bioenergy-induced increases in intracellular free calcium concentrations are mediated by the Na+/Ca2+ exchanger and L-type calcium channel. Mol Cell Biochem 271:51-59, 2005.
76. Kiang JG. Lu X, Tabaku LS, Bentley TB, Atkins JL, and Tsokos GC. Resuscitation with lactated Ringers solution limits the expression of molecular events associated with lung injury after hemorrhage. J Appl Physiol 98:550-556, 2005.
77. Krishnan S, Kiang JG, Fisher CU, Nambiar MP, Nguyen HT, Kyttaris VC, Chowdhury B, Rus V, Tsokos GC. Increased caspase-3 expression and activity contributes to reduced CD3 expression in Systemic Lupus Erythematosus T cells. J Immunol 175:3417-3423, 2005.
78. Kiang JG, Bowman DP, Lu X, Li Yansong, Ding XZ, Zhao B, Juang YT, Atkins JL, Tsokos GC. Geldanmaycin treatment prevents hemorrhage-induced ATP loss in mouse organs by overexpressing HSP-70 and activating pyruvate dehydrogenase. Am J Physiol 291:G117-G127, 2006.
79. Tsen KT, Tsen SWD, Kiang JG. Lycopene is more potent than bata carotene in the neutralization of singlet oxygen: role of energy transfer probed by ultrafast Raman spectroscopy. J Biomed Optics 11:064025 (6 pages), 2006.
80. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN: Dependence on the injected carrier density. App Physics Lett 89:11211 (3 pages), 2006.
81. Tsen KT, Kiang JG, Ferry DK, Kochelap VA, Komirenko SM, Kim KW, Morkoc H. Subpicosecond Raman studies of electric-field-induced optical phonon instability in an In0.53Ga0.47As-based semiconductor nanostructure. J Phys: Condens Matter 18:7961-7974, 2006.
82. Kiang JG, Tsen KT. Biology of hypoxia. Chin J Physiol 49:223-233, 2006.
83. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Observation of the low frequency vibrational modes of bacteriophage M13 in water by Raman spectroscopy. Virology J 3:79 (11 pages), 2006.
84. Tsen KT, Dykeman E, Sankey OF, Lin N-T, Tsen S-WD, Kiang JG. Raman scattering studies of the low frequency vibrational modes of bacteriophage M13 in water. Nanotecnology 17:5474-5479, 2006.
85. Tsen KT, Kiang JG, Ferry DK, and Morkoc H. Subpicosecond time-resolved Raman studies of field-induced transient transport in an -based p-i-n semiconductor nanostructure. App Physics Lett, 89: 262101 (3 pages), 2006.
86. Tsen KT, Kiang JG, and Ferry DK. Subpicosecond transient Raman scattering studies of field-induced electron transport in an -based p-i-n nanostructure: Direct observation of the effects of electron momentum randomization. J Phys: Condens Matter 18:L585-L592, 2006.
87. Kiang JG, Peckham RM, Duke LE, Chaudry IH, Tsokos GC. Androstenediol inhibits trauma-hemorrhage-induced increase in caspase-3 by downregulating inducible nitric oxide synthase pathway. J App Physiol 102: 933-941, 2007.
88. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Probing the low frequency vibrational modes of viruses with Raman scattering -- bacteriophage M13 in water. J Biomed Optics. 12: 024009 (6 pages), 2007.
89. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN. Proc of SPIE 6473: 64730Q-1 – 64730Q-12, 2007.
90. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Studies of longitudinal optical phonons in GaN by sybpicosecond time-resolved Raman Spectroscopy. Proc of SPIE 6471: 64710X-1 – 64710X-10, 2007.
91. Kiang JG, Bowman DP, Lu X, Li Y, Wu BW, Loh HH, Tsen KT, Tsokos GC. Geldanmaycin treatment inhibits hemorrhage-induced increases in caspase-3 activity: Role of inducible nitric oxide synthase. J App Physiol 103: 1045-1055, 2007.
92. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Direct measurements of the lifetimes of longitudinal optical phonon modes and their dynamics in InN. App Physics Lett 90: 152107 (3 pages), 2007.
93. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Subpicosecond time-resolved Raman studies of electron-longitudinal optical phonon interactions in InN. App Physics Lett 90: 172108 (3 pages), 2007.
94. Tsen KT, Kiang JG, Ferry DK, Lu H, Schaff WJ, Lin HW, Gwo S. Electron-density dependence of longitudinal-optical phonon lifetime in InN studied by subpicosecond time-resolved Raman spectroscopy. J Phy Condens Matter 19: 236219 (8 pages), 2007.
95. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by coherent excitations with low power visible femtosecond laser. Virology J 4:50 (6 pages), 2007.
96. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses with a very low power visible femtosecond laser. J Physics: Condens Matter 19:322102 (9 pages), 2007.
97. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by laser-driven coherent excitations via impulsive stimulated Raman scattering process. J Biomed Optics 12:064030 (6 pages), 2007.
98. Tsen KT, TsenS-W D, Sankey OF, Kiang JG. Selective inactivation of microorganisms by near-IR femosecond laser pulses. J Phy Condens Matter 19: 472201 (7 pages), 2007.
99. Kiang JG, Krishnan S, Lu X, Li Y. Inhibition of inducible nitric oxide synthase protects human T cells from hypoxia-induced injury. Mol Pharmacol 73:738-747, 2008.
100. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kiang JG. Selective inactivation of human immunodeficiency virus with subpicosecond near-infrared laser pulses. J Phys Condens matter 20:25220 (4 pages), 2008.
101. Atkins JL, Hammamiech R, Jett M, Gorbounov NV, Asher LV, Kiang JG. α-Defensin-4 and asymmetric dimethyl arginine (ADMA) increase in mesenteric lymph after hemorrhage in anesthetized rats. Shock 30: 411-146, 2008.
102. Tsen KT, Tsen S-W D, Chang C-L, Hung C-F, Wu T-C, Ramakrishna K, Mossman K, Kiang JG. Inactivation of viruses with a femtosecond laser via impulsive stimulated Raman scattering. In: Optical Interactions with Tissue and Cells XIX (edited by Steven L. Jacques, William P. Roach, Robert J. Thomas), Proc. of SPIE 6854: 68540N1-6854N10, 2008.
103. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Dynamics of LO phonons in InN studied by subpicosecond time-resolved Raman spectroscopy. In: Ultrafast Phenomena in Semiconductors and Nanostructure Materials XII (edited by J.J. Song, K.T. Tsen, M. Betz and A. Elezzabi), Proc. of SPIE Vol. 6892: 689206 (12 pages), 2008.
104. Kiang JG, Kiang SC, Bowman PD. 17-DMAG inhibits hemorrhage-induced injury in small intestine and lung by inactivating caspase-3. International Proceedings of International Shock Congress K628C0171:23-27, 2008.
105. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kibler K, Jacob B, Kiang JG. Selective inactivation of human immunodeficiency virus with an ultrashort pulsed laser. Proc. of SPIE 7175: 717510-1 – 717510-8, 2009.
106. Kiang JG, Smith JA, and Agravante NG. Geldanamycin analog 17-DMAG inhibits iNOS and caspases in gamma irradiated human T cells. Radiat Res 172: 321-330, 2009.
107. Gorbunov NV, Kiang JG. Up-regulation of Autophagy in the Small Intestine Paneth Cell in Response to Total-Body γ-Irradiation. J Pathol 219: 242-252, 2009.
108. Jiao W, Kiang JG, Cary L, Elliott TB, Pellmar TC, Ledney GD. COX-2 inhibitors are contraindicated for therapy of combined injury. Radiat Res 172: 686-697, 2009.
109. Tsen KT, Tsen S-WD, Fu Q, Lindsay SM, Kibler K, Jacobs B, Wu TC, Karanam B, Jagu S, Roden RBS, Hung C-F, Sankey OF, Ramakrishna B, Kiang JG. Photonic approach to the selective inactivation of viruses with a near-infrared subpicosecond fiber laser. J Biomed Opt 14: 064042 (10 pages), 2009.
110. Kiang JG, Jiao W, Cary L, Mog SR, Elliott TB, Pellmar TC, Ledney GD. Wound trauma increases radiation-induced mortality by increasing iNOS, cytokine concentrations, and bacterial infections. Radiate Res 173: 319-332, 2010.
111. Kiang JG, Garrison BR, Gorbunov NV. Radiation combined injury: DNA damage, apoptosis, and autophagy. Adapt Med 2: 1-10, 2010. doi: 10.4247/AM.2010.ABA004.
112. Daly MJ, Gaidamakova EK, Matrosova VY, Kiang JG, Fukumoto R, Wehr NB, Viteri G, Berlett BS, Levine RL. Small molecule proteome-shield in Deinococcus radiodurans. PLoS One 5(9): e12570 (15 pages), 2010.
113. Gorbunov NV and Kiang JG. Activation of IL-1β pathway and augmentation of Paneth cell α-defensin-4 in small intestine following total-body γ-irradiation. Intl J Immunopathol Pharmacol 23: 1111-1123, 2010.
114. Kiang JG, Smith JA, Agravante NG, Gorbunov NV. Geldanamycin analog 17-DMAG has radioprotective activity in mice. Radiat Res, in review.
115. Fukumoto R, Kiang JG. Geldanamycin analog 17-DMAG limits apoptosis in human peripheral blood cells by inhibition of p53 activation and its interaction with heat shock protein 90 kDa after ionizing radiation. Radiat Res 176: 333-345, 2011.
116. Kiang JG, Agravante NG, Smith JT, Bowman PD. 17-DMAG increases Bcl-2 and inhibits hemorrhage-induced increases in iNOS activation, caspase-3 activity and TNF-a. Cell & Bioscience 1: 21 (10 pages), 2011.
117. Tsen KT, Tsen SWD, Fu Q, Lindsay SM, Li Z, Yan H, Cope S, Vaiana S, Kiang JG. Studies of inactivation of encephalomyocaditis virus, M13 bacteriophage and Salmomella typhimurium by using a visible femtosecond laser irradiation: insight into the possible inactivation mechanisms. J Biomed Optics 16: 078003 (11 pages), 2011.
118. Whitnall MH, Cary LH, Moroni M, Ngudiankama BF, Landauer MR, Singh VK, Ghosh SP, Kulkarni S, Miller AC, Kiang JG, Srinivasan V, Xiao M. United States Armed Forces Radiobiology Research Institute countermeasures program and related policy questions. Proceedings,Hiroshima University, 2012.
119. Kiang JG, Garrison BR, Burns TM, Zhai M, Dews IC, Ney PH, Fukumoto R, Cary LH, Elliott TB, Ledney GD. Wound trauma alters ionizing radiation dose assessment. Cell Bioscience 2: 20 (12 pages), 2012.
120. Tsen S-W D, Wu TC, Kiang JG, Tsen KT. Prospects for a novel ultrashort pulsed laser technology for pathogen inactivation. J Biomed Sci 19: 62 (11 pages), 2012.
121. Kiang JG. Overview of biological effects of irradiation combined injury. NATO-HFM-223-P5:1-18, 2012.
122. Fukumoto R, Cary LH, Gorbunov NV, Elliott TB, Kiang JG. Ciprofloxacin modulates cytokine profiles, accelerates bone marrow recovery and mitigates ileum injury after radiation combined with wound trauma. PLoS One 8: e58389 (11 pages), 2013. doi: 10.1371/journal.pone.0058389. PMID: 23520506
123. Gorbunov NV, Garrison BR, McDaniel DP, Zhai M, Liao1 P-J, Nurmemet N, Kiang JG. Adaptive redox response of mesenchymal stromal cells to stimulation with lipopolysaccharide inflammagen: mechanisms of remodeling of tissue barriers in sepsis. Oxid Med Cell Longev 2013: 186795 (16 pages), 2013. doi: 10.1155/2013/186795. PMID: 23710283
124. Lu X, Nurmemet D, Bolduc DL, Elliott TB, Kiang JG. Radioprotective effects of oral 17-DMAG in mice: Bone marrow and small intestine. Cell Bioscience 3: 36 (16 pages), 2013. doi: 10.1186/2045-3701-3-36. PMID: 24499553
125. Kiang JG, Ledney GD. Skin injuries reduce survival and modulate corticosterone, C-reactive protein, complement component 3, IgM, and prostaglandin E2 after whole-body reactor-produced mixed field (n + γ-photons) irradiation. Oxid Med Cell Longev, 2013: 821541 (10 pages), 2013. doi: 10.1155/2013/821541. PMID: 24175013
126. Kiang JG, Garrison BR, Smith JT, Fukumoto R. Ciprofloxacin as a potential radio-sensitizer to tumor cells and a radioprotectant for normal cells: Differential effects on -H2AX formation, p53 phosphorylation, Bcl-2 production, and cell death. Cell Mol Biochem 393: 133-143, 2014. doi: 10.1007/s11010-014-2053-z. PMID: 24802382
127. Kiang JG, Fukumoto R. Ciprofloxacin increases survival after ionizing irradiation combined injury: gamma-H2AX formation, cytokine/chemokine, and red blood cells. Health Physics 106: 720-726, 2014. doi: 10.1097/HP.0000000000000108. PMID: 24776905
128. Fukumoto R, Burns TM, Kiang JG. Ciprofloxacin Enhances Stress Erythropoiesis in Spleen and Increases Survival after Whole-Body Irradiation Combined with Skin-Wound Trauma, PLoS One 9(2): e90448, 2014. doi: 10.1371/journal.pone.0090448. PMID: 24587369
129. Kiang JG, Zhai M, Liao P-J, Bolduc DL, Elliott TB, Gorbunov NV. Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn. Oxid Med Cell Longev 2014: 481392 (10 pages), 2014. doi: 10.1155/2014/481392. PMID: 24738019
130. Kiang JG, Zhai M, Liao P-J, Elliott TB, Gorbunov NV. Ghrelin therapy improves survival after whole-body ionizing irradiation combined with wound or burn: Amelioration of leukocytopenia, thrombopenia, splenomegaly, and bone marrow injury. Oxid Med Cell Longev 2014: 215858, 2014. doi: 10.1155/2014/215858. PMID: 25374650
131. Gorbunov NV, Elliott TB, McDaniel DP, Zhai M, Liao P-J, Kiang JG. Mitophagy and mitochondrial remodeling in mouse mesenchymal stromal cells following a challenge with Staphylococcus epidermidis. J Cell Mol Med 19:1133-1150, 2015. doi: 10.1111/jcmm.12518. PMID: 25721260
132. Kiang JG, Gorbunov NV. Bone marrow mesenchymal stem cells increases survival after ionizing irradiation combined with wound trauma: Characterization and therapy. J Cell Sci Ther 5:190 (8 pages), 2014. doi: 10.4172/2157-7013.1000190
133. Elliott TB, Bolduc DL, Ledney GD, Kiang JG, Fatanmi OO, Wise S, Romaine PLP, Newman VL, Singh VK. Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in mice exposed to radiation and combined injury. Int J Radiat Biol 91(9):690-702, 2015. doi: 10.3109/09553002.2015.1054526. PMID: 25994812
134. Swift JM, Smith JT, Kiang JG. Ciprofloxacin therapy mitigates ATP loss after irradiation combined with wound trauma: Preservation of pyruvate dehydrogenase and inhibition of pyruvate dehydrogenase kinase 1. Radiat Res 183: 684-692, 2015. PMID: 26010714
135. Swift JM, Smith JT, Kiang JG. Hemorrhage Trauma Increases Radiation-Induced Trabecular
Bone Loss and Marrow Cell Depletion in Mice. Radiat Res 183: 578-583, 2015. doi: 10.1667/RR13960.1 PMID: 25897554
136. Swift JM, Swift SN, Smith JT, Kiang JG, Allen MR. Skin wound trauma, following high-dose radiation exposure, amplifies and prolongs skeletal tissue loss. Bone 81: 487-494, 2015. doi: 10.1016/j.bone.2015.08.022 PMID: 26335157
137. Islam A, Bolduc DL, Zhai M, Kiang JG, Swift JM. Daily Captopril Dosing Increases Survival after Whole-Body Ionizing Irradiation but Decreases Survival after in combination with Combined Burn Trauma in Mice. Radiat Res 184:273-279, 2015. doi: 10.1667/RR14113.1. PMID: 26305295
138. Kiang JG, Smith JT, Anderson MN, Swift JM, Gupta P, Balakathiresan N, Maheshwari RK. Hemorrhage exacerbates radiation effects on survival, leukocytopenia, thrombopenia, erythropenia, bone marrow cell depletion and hematopoiesis, and inflammation-associated microRNAs expression in kidney. PLoS ONE 10:e0139271, 2015. doi: 10.1371/journal.pone.0139271. PMID: 26422254
139. Klionsky DJ…Kiang JG…Zughaler SM. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12: 1-222, 2016. PMID: 26799652
140. Kiang JG. Adult mesenchymal stem cells and radiation injury. Health Phys 111:198-203, 2016. doi: 10.1097/HP.0000000000000459. PMID: 27356065
141. Gupta P, Gayen M, Smith JT, Matrosova VY, Gaidamakova EK, Daly MJ, Kiang JG, Maheshwari RK. MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation. PLoS One 11: e0160575, 2016. doi: 10.1371/journal.pone.0160575. PMID: 27500529
142. Kiang JG. Exacerbation of mild hypoxia on acute radiation syndrome and subsequent mortality. Adaptive Med 9(1): 28-33, 2017. doi: 10.4247/AM.2017.ABG170
143. Kiang JG, Zhai M, Liao P.-J., Ho C, Gorbunov NV, Elliott TB. Thrombopoietin receptor agonist mitigate hematopoietic acute radiation syndrome and improves survival after whole-body ionizing irradiation followed by wound trauma. Mediators of Inflammation 2017:7582079, 2017. doi: 10.1155/2017/7582079 PMID: 28408792
144. Kiang JG, Zhai M, Bolduc DL, Smith JT, Anderson MN, Ho C, Lin B, Jiang S. Combined therapy of pegylated-G-CSF and Alx4100TPO improves survival and mitigate acute radiation syndrome after whole-body ionizing irradiation alone and followed by wound trauma. Radiat Res 188:476-490, 2017. doi: 10.1667/RR14647.1 PMID: 28850300
145. Kiang JG, Smith JT, Anderson MN, Elliott TB, Gupta P, Balakathiresan N, Maheshwari RK, Knollmann-Ritschel B. Hemorrhage enhances cytokine, complement component 3, and caspase-3, and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury. PLoS ONE 12(9):e0184393, 2017. doi: 10.1371/journal.pone.0184393.PMID: 28934227
146. Gorbunov NV, Kiang JG. Ghrelin therapy decreases incidents of intracranial hemorrhage in mice after whole-body ionizing irradiation combined with burn trauma. Int J Mol Sci 18(8). pii: E1693, 2017. doi: 10.3390/ijms18081693. PMID: 28771181
147. Kiang JG, Smith JT, Hegge SR, Ossetrova N. Circulating cytokine/chemokine concentrations respond to ionizing radiation doses but not radiation dose rates: granulocyte-colony stimulating factor and interleukin-18. Radiat Res, in press, 2018.
148. Kiang JG, Anderson MN, Smith JT. Ghrelin therapy sustains granulocyte colony-stimulating factor and keratinocyte factor to mitigate hematopoietic syndrome and spleen after whole-body ionizing irradiation combined with wound. Cell Biosci 8:27, 2018. doi: 10.1186/s13578-018-0225-3.
149. Li X, Cui W, Hull L, Smith JT, Kiang JG, Xiao M. Effects of low-moderate doses of γ-radiation on mouse hematopoietic and immune system. Radiat Res, in review, 2018.
E-Book (1)
1. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. Cell Biology Research Progress, Nova Science Publishers, INC. Hauppauge, NY. ISBN: 978-1-62417-374-5 http://www.novapublishers.com, 2012.
Book chapters (10)
1. Yan X, Lu PY, and Kiang JG. Qigong: basic science studies in Biology. In: Healing, Intention, and Energy medicine Science, Research Methods and Clinical Implications. (Eds. WB Jonas and C Crawford) Churchill Livingstone, London, UK pp. 103-119, 2003.
2. Kiang JG and McClain DE. Heat stress. In: Combat Medicine Basic and Clinical Research in Military, Trauma, and Emergency Medicine (Eds. GC Tsokos and JL Atkins), Humana Press, New Jersey, pp. 83-101, 2003.
3. Kiang JG. Human bioenergy effects at the cellular and molecular level. In: Life and Mind In Search of Physical Basis (ed. S. Savva), Trafford Publishing, Victoria BC, Canada, pp. 117-137, 2007.
4. Tsen KT, Tsen SWD, Dykeman EC, Sankey OF, Kiang JG. Inactivation of viruses with femtosecond laser pulses. In: Contemporary Trends in Bacteriophage research (Ed: Horace T. Adams), Nova Science Publishers, NY, ISBN: 978-1-60692-181-4, pp. 151-177, 2009.
5. Kumar KS, Kiang JG, Whitnall MH, Hauer-Jensen M. Perspectives in radiological and nuclear countermeasures. In: Textbook of Military Medicine, pages 239-266, 2012.
6. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. In: Autophagy: Principles, Regulation and Roles in Disease (ed: Gorbunov NV), Nova Science Pulbishers, INC. Hauppauge, NY. 2012.
7. Gorbunov NV, Garrison BR, Zhai M, McDaniel DP, Ledney GD, Elliott TB, Kiang JG. Autophagy-mediated defense response of mouse mesenchymal stromal cells (MSCs) to challenge with Escherichia coli. In: Protein Interaction / Book 1; ISBN 979-953-307-577-7. Eds.: Cai J and Wang H. InTech Open Access Publisher; www.intechweb.org. pp. 23-44, 2012.
8. Kiang JG, Fukumoto R, Gorbunov NV. Lipid peroxidation after ionizing irradiation leads to apoptosis and autophagy. In: Lipid Peroxidation; ISBN 980-953-307-143-0. Eds.: Angel Catala, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp.261-278, 2012.
9. Gorbunov NV, Elliott TB, McDaniel DP, Lund K, Liao PJ, Zhai M, Kiang JG. Up-regulation of autophagy defense mechanisms in mouse mesenchymal stromal cells in response to ionizing irradiation followed by bacterial challenge. In: Autophagy, ISBN 980-953-307-971-9. Ed: Yannick Bailly, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp. 331-350, 2013.
10. Kiang JG. Characterization and therapeutic uses of adult mesenchymal stem cells. In: Stem Cell Toxicity and Medicine (ed. S.C. Sahu). Wiley & Sons, West Sussex, pp. 288-301, 2016.
Representative publications, projects, and/or deployments
- Patent 1. Method of Inhibiting Inflammatory Response, Wei ET, and Kiang JG, U.S. Patent 4,801,612 (January 31, 1989)
- Patent 2. System and method for diminishing the function of microorganisms with a visible femtosecond laser, Tsen KT, Tsen SWD, and Kiang JG, U.S. Patent 60,932,668 (June 1, 2007); South Africa Patent 2010/00380 (Sep 29. 2010); China Patent CN101971008B (May 15, 2012)
- Patent 3. 17-DMAG as a radioprotectant, Kiang JG, U.S. Provisional Patent 61,122,041 (Dec 11, 2008)
- Best Poster Award, Society of Chinese Bioscientists in America, 3-18-2017
- AFRRI Research Award, AFRRI, 2016
- Research and Development Achievements Award, U.S. Department of Army, U.S. Department of Defense, 2006
- DOD Female Science, Technology, Engineering, Mathematics Role Models, 2006
- Order of Military Medical Merit, 2006
- Outstanding Alumni Award 2005, Fu-Jen Catholic University, 2005
- The 20th Century Award for Achievement in Life Sciences, International Biographical Centre of Cambridge, England, 2000
Bibliography
- Kiang JG, Anderson MN, Smith JT. Ghrelin therapy sustains granulocyte colony-stimulating factor and keratinocyte factor to mitigate hematopoietic syndrome and spleen after whole-body ionizing irradiation combined with wound. Cell Biosci 8:27, 2018. doi: 10.1186/s13578-018-0225-3.
- Gorbunov NV, Kiang JG. Ghrelin therapy decreases incidents of intracranial hemorrhage in mice after whole-body ionizing irradiation combined with burn trauma. Int J Mol Sci 18(8). pii: E1693, 2017. doi: 10.3390/ijms18081693. PMID: 28771181
- Kiang JG, Smith JT, Anderson MN, Elliott TB, Gupta P, Balakathiresan N, Maheshwari RK, Knollmann-Ritschel B. Hemorrhage enhances cytokine, complement component 3, and caspase-3, and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury. PLoS ONE 12(9):e0184393, 2017. doi: 10.1371/journal.pone.0184393.PMID: 28934227
- Kiang JG, Smith JT, Anderson MN, Swift JM, Gupta P, Balakathiresan N, Maheshwari RK. Hemorrhage exacerbates radiation effects on survival, leukocytopenia, thrombopenia, erythropenia, bone marrow cell depletion and hematopoiesis, and inflammation-associated microRNAs expression in kidney. PLoS ONE 10:e0139271, 2015. doi: 10.1371/journal.pone.0139271. PMID: 26422254
- Swift JM, Smith JT, Kiang JG. Ciprofloxacin therapy mitigates ATP loss after irradiation combined with wound trauma: Preservation of pyruvate dehydrogenase and inhibition of pyruvate dehydrogenase kinase 1. Radiat Res 183: 684-692, 2015. PMID: 26010714
- Kiang JG, Gorbunov NV. Bone marrow mesenchymal stem cells increases survival after ionizing irradiation combined with wound trauma: Characterization and therapy. J Cell Sci Ther 5:190 (8 pages), 2014. doi: 10.4172/2157-7013.1000190
- Kiang JG, Zhai M, Liao P-J, Elliott TB, Gorbunov NV. Ghrelin therapy improves survival after whole-body ionizing irradiation combined with wound or burn: Amelioration of leukocytopenia, thrombopenia, splenomegaly, and bone marrow injury. Oxid Med Cell Longev 2014: 215858, 2014. doi: 10.1155/2014/215858. PMID: 25374650
- Fukumoto R, Burns TM, Kiang JG. Ciprofloxacin Enhances Stress Erythropoiesis in Spleen and Increases Survival after Whole-Body Irradiation Combined with Skin-Wound Trauma, PLoS One 9(2): e90448, 2014. doi: 10.1371/journal.pone.0090448. PMID: 24587369
- Kiang JG, Jiao W, Cary L, Mog SR, Elliott TB, Pellmar TC, Ledney GD. Wound trauma increases radiation-induced mortality by increasing iNOS, cytokine concentrations, and bacterial infections. Radiate Res 173: 319-332, 2010.
- Kiang JG, Krishnan S, Lu X, Li Y. Inhibition of inducible nitric oxide synthase protects human T cells from hypoxia-induced injury. Mol Pharmacol 73:738-747, 2008.
Vijay K. Singh, Ph.D.
Name: Vijay K. Singh, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Prof.
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Radiation Biology
Countermeasures
Email:
Office Phone:
(301) 295-2347
Department Website:
Education
1983 Ph.D., Central Drug Research Institute (KU), India
1978 M.Sc., Kanpur University, India
1975 B.Sc., Magadh University, India
1978 M.Sc., Kanpur University, India
1975 B.Sc., Magadh University, India
Biography
Mechanism of radiation injury and advanced development of radiation countermeasures
My laboratory focuses attention on the molecular basis of radiation injury which results in acute radiation syndromes (ARS), and the mechanism of action of potential radiation countermeasures. Our ultimate goal is to develop radiation countermeasures to protect military personnel, first responders and civilians from succumbing to ARS following radiation exposure whether it is accidental or as a result of deliberate attack. To achieve this goal we are currently investigating the mechanism of action of gamma-tocotrienol (GT3, an isomer of Vitamin E), Ex-RAD (a chlorobenzylsulphone derivative), toll-like receptor (TLR) ligands (CBLB502), and anti-ceramide antibody at the cellular level, by evaluating cell signaling pathways (cytokine expression, p53 pathway, TLR activation) including DNA damage and repair pathways.
In collaboration with corporate partners, my lab is developing several radiation countermeasures which are under advanced stages of development. CBLB502 and anti-cermide antibody appear to be promising. Ex-RAD has been shown to have both radioprotective and radiomitigative properties. Ex-RAD protects the hematopoietic system and is able to increase survival of irradiated mice by alleviating the severe radiation induced pancytopenia and restoring select bone marrow functions through the up-regulation of the PI3-kinase/AKT pathways and pathways involved with the DNA damage response and DNA repair. Ex-RAD studies have received significant funding from DMRDP (DoD) and BARDA (HHS).
My lab is also working to develop GT3, as a radiation countermeasure in collaboration with Prof. Martin Hauer-Jensen. It has shown great promise in rodent model, capable of mobilizing progenitors, and its radioprotective efficacy is mediated through G-CSF in murine model. Recently, we found that a single administration of GT3, without additional support (fluids, antibiotics, blood products, etc.), was just as effective as multiple administrations of G-CSF, the current gold standard of radiation countermeasures approved by US FDA, with full support. Based on the promising results of our pilot study using the large animal model, we have received funding from CDMRP (DoD) for the advanced development of GT3.
Additionally, we are working to develop a novel anti-ceramide antibody in collaboration with Prof. Richard Kolesnick of Sloan Kettering and Ceramide Theraprutics as a radiation countermeasure, capable of being administered prior to or after radiation exposure. Studies have indicated that this potential countermeasure inhibits ceramide-mediated endothelial apoptosis, which provides significant protection against radiation induced, potentially fatal, gastrointestinal syndrome. Additional studies have shown that a single chain variable fragment of the full length antibody molecule is effective in doses one tenth of the full length version. This project had been supported by DMRDP (DoD). Additional countermeasures being investigated are CBLB612, CBLB613, and myeloid progenitors in collaboration with various academic and corporate partners with support from various funding agencies such as BARDA, NIAID, JPC7, CDMRP, and DMRDP.
My laboratory focuses attention on the molecular basis of radiation injury which results in acute radiation syndromes (ARS), and the mechanism of action of potential radiation countermeasures. Our ultimate goal is to develop radiation countermeasures to protect military personnel, first responders and civilians from succumbing to ARS following radiation exposure whether it is accidental or as a result of deliberate attack. To achieve this goal we are currently investigating the mechanism of action of gamma-tocotrienol (GT3, an isomer of Vitamin E), Ex-RAD (a chlorobenzylsulphone derivative), toll-like receptor (TLR) ligands (CBLB502), and anti-ceramide antibody at the cellular level, by evaluating cell signaling pathways (cytokine expression, p53 pathway, TLR activation) including DNA damage and repair pathways.
In collaboration with corporate partners, my lab is developing several radiation countermeasures which are under advanced stages of development. CBLB502 and anti-cermide antibody appear to be promising. Ex-RAD has been shown to have both radioprotective and radiomitigative properties. Ex-RAD protects the hematopoietic system and is able to increase survival of irradiated mice by alleviating the severe radiation induced pancytopenia and restoring select bone marrow functions through the up-regulation of the PI3-kinase/AKT pathways and pathways involved with the DNA damage response and DNA repair. Ex-RAD studies have received significant funding from DMRDP (DoD) and BARDA (HHS).
My lab is also working to develop GT3, as a radiation countermeasure in collaboration with Prof. Martin Hauer-Jensen. It has shown great promise in rodent model, capable of mobilizing progenitors, and its radioprotective efficacy is mediated through G-CSF in murine model. Recently, we found that a single administration of GT3, without additional support (fluids, antibiotics, blood products, etc.), was just as effective as multiple administrations of G-CSF, the current gold standard of radiation countermeasures approved by US FDA, with full support. Based on the promising results of our pilot study using the large animal model, we have received funding from CDMRP (DoD) for the advanced development of GT3.
Additionally, we are working to develop a novel anti-ceramide antibody in collaboration with Prof. Richard Kolesnick of Sloan Kettering and Ceramide Theraprutics as a radiation countermeasure, capable of being administered prior to or after radiation exposure. Studies have indicated that this potential countermeasure inhibits ceramide-mediated endothelial apoptosis, which provides significant protection against radiation induced, potentially fatal, gastrointestinal syndrome. Additional studies have shown that a single chain variable fragment of the full length antibody molecule is effective in doses one tenth of the full length version. This project had been supported by DMRDP (DoD). Additional countermeasures being investigated are CBLB612, CBLB613, and myeloid progenitors in collaboration with various academic and corporate partners with support from various funding agencies such as BARDA, NIAID, JPC7, CDMRP, and DMRDP.
Representative publications, projects, and/or deployments
- G1B23687 Determination of radiation dose response for the AFRRI LINAC and subsequent non-clinical studies to evaluate potential medical countermeasures as mitigators of hematopoietic and/or low dose GI syndromes (H-ARS; GI-ARS) in an NHP model. Biomedical Advanced Research and Development Authority (BARDA), $8,535,865, September 15, 2015 – September 14, 2019
- G1B22927 Advanced development of gamma-tocotrienol as a radiation countermeasure. Congressionally Directed Medical Research Programs (CDMRP), $7,811,978, September 21, 2015 – September 20, 2019.
- G2B2HF Evaluation of radiation mitigators in nonhuman primates with supportive care. National Institute of Allergy and Infectious Diseases (NIAID), FY 2016 $406,581, FY 2017 $1,264,698, September 2015 – Sepetember 2017, Open ended, yearly renewal expected every year with additional budget.
- NAB22586 Advanced development of Ex-RAD as a radiomitigator. Defense Medical Research and Development Program (DMRDP), $ 1,198,000, April 2014 – September 2017
- G1B24024 Advanced Development of BIO 300 for Acute Radiation Syndrome and Delayed Effects of Acute Radiation Exposure, Congressionally Directed Medical Research Programs (CDMRP), $1,195,189, October 2016 – September 2019
- RAB24402 Biomarkers for radiation injury: Integrative omics study, AFRRI, $240,000, November 11, 2016 – September 30, 2019
- AFR-B2-4365 Development of Bio 301: An encapsulated nano-genistein therapy, Congressionally Directed Medical Research Programs (CDMRP), $712,295, POP to be negotiated
Bibliography
Biosketch Link:
- Singh VK, Seed TM: A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures. Int J Radiat Biol (in press: DOI: 10.1080/09553002.2017.1332438), 2017.
- Singh VK, Garcia M, Seed TM: A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status. Int J Radiat Biol (in press: DOI: 10.1080/09553002.2017.1338782), 2017.
- Singh VK, Hanlon BK, Santiago PT, Seed TM: A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part III. Countermeasures under early stages of development along with ‘standard of care’ medicinal and procedures not requiring regulatory approval for use. Int J Radiat Biol (in press: DOI: 10.1080/09553002.2017.1332440), 2017.
- Fendler W, Malachowska B, Meghani K, Konstantinopoulos PA, Guha C, Singh VK, Chowdhury C: Evolutionarily conserved serum microRNAs can predict radiation-induced fatality in non-human primates. Sci Transl Med 9:eaal2408, 2017
- Singh VK, Fatanmi OO, Wise SY, Newman VL, Romaine PLP, Seed TM: The potentiation of the radioprotective efficacy of two medical countermeasures, gamma-tocotrienol and amifostine, by a combination prophylactic modality. Radiat Prot Dosimetry 172:302-310, 2016.
- Singh VK, Kulkarni S, Fatanmi OO, Wise SY, Newman VL, Romaine PLP, Hendrickson H, Gulani J, Ghosh SP, Kumar KS, Hauer-Jensen M: Radioprotective efficacy of gamma-tocotrienol in nonhuman primates. Radiat Res 185:285-298, 2016.
- Krivokrysenko VI, Toshkov I, Gleiberman A, Krasnov P, Shyshynova I, Bespalov I, Maitra R, Narizhneva N, Singh VK, Whitnall MH, Purmal A, Shakhov A, Gudkov A, Feinstein E: TLR5 agonist Entolimod mitigates acute radiation syndrome in non-human primates. PLoS One 10:e0135388, 2015.
- Elliott TB, Bolduc DL, Ledney GD, Kiang JG, Fatanmi OO, Wise SY, Romaine PLP, Newman VL, Singh VK: Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in mice exposed to radiation and combined injury. Int J Radiat Biol 91:690-702, 2015.
- Dalgard CL, Jacobowitz DM, Singh VK, Saleem KS, Ursano RJ, Starr JM, Pollard HB: A novel analytical brain block tool to enable functional annotation of discriminatory transcript biomarkers among discrete regions of the fronto-limbic circuit in primate brain. Brain Res 1600:42-58, 2015.
- Singh VK, Wise SY, Fatanmi OO, Scott J, Romaine PLP, Newman VL, Verma A, Elliott TB, Seed TM: Progenitors mobilized by gamma-tocotrienol as an effective radiation countermeasure. PLoS ONE 9:e114078, 2014.
PHA - National Faculty
Brian M. Cox, Ph.D.
Name: Brian M. Cox, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Professor of Pharmacology & Neuroscience
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Neuropharmacology - opiate drugs & substance use disorderds
Traumatic brain injury - mechanisms & biomarkers
Email:
Office Phone:
(301) 295-3260
Education
Ph.D. in Pharmacology, St. Mary's Hospital Medical School, University of London, London, United Kingdom, 1965
B.Sc. in Pharmacolopy, Chelsea College of Science & Technology, University of London, London, United Kingdom, 1962
B.Sc. in Pharmacolopy, Chelsea College of Science & Technology, University of London, London, United Kingdom, 1962
Biography
Dr. Cox is currently Professor of Pharmacology and Neuroscience at the Uniformed Services University (USU) in Bethesda MD. He received his initial training in pharmacology from Chelsea College of Science and Technology in London, UK, and received a Ph.D. in Pharmacology from St. Mary's Hospital Medical School, University of London, UK. After teaching pharmacology to pharmacy and science students at Chelsea College of Science and Technology of the University of London for eight years, he became a visiting scientist in the Department of Pharmacology at Stanford University, and was appointed Consulting Associate Professor of Pharmacology at Stanford in 1978. Concurrently, he served as Laboratory Research Group Director and then Associate Director for Research for the Addiction Research Foundation in Palo Alto, CA. In 1981, Dr. Cox moved to his current position at USU, where he served as chair of the Department of Pharmacology from 1995 until 2007. He currently also serves as an Assistant Dean for Graduate Education at USU.
For most of his career Dr. Cox's research has focused on characterizing the receptors utilized by opiate drugs and their endogenous ligands, and in defining potential physiological and pathophysiological roles for endogenous opioids and other neuropeptides. His lab is currently studying factors affecting peptide and receptor expression, and changes at the cellular level induced by drugs of abuse, severe stress, or neural injury. He now leads the Biomarkers Group of the USU/NIH Center for Neuroscience and Regenerative Medicine, evaluating neurochemical mechanisms underlying traumatic brain injury and potential biomarkers for TBI.
Dr. Cox has been a member of the American Society for Pharmacology and Experimental Therapeutics (ASPET) since 1976. He served as Secretary/Treasurer of (1997-2000), and was elected President of ASPET for 2009-2010. He chaired the ASPET Board of Publications Trustees from 2002-2007. He has served on the Editorial Boards of the Journal of Pharmacology and Experimental Therapeutics (1998 – present), Molecular Pharmacology (1981-1994), and Molecular Interventions (2000-2002). Dr. Cox was a member of the ASPET Scientific Program Committee from 1986-1990 and Chaired the Program Committee from 1990-1996. He served as ASPET’s representative to the Experimental Biology Program Committee from 1991-1994 and served on the Experimental Biology Board from 1996-1999 (as Chairman for 1998-1999). He is currently serving a second term as a member of the Board of Directors of the Federation of American Societies of Experimental Biology.
Dr. Cox was the ASPET representative to the International Advisory Committee for the 1998 International Union of Pharmacology (IUPHAR) Congress in Munich, Germany, and chaired the IUPHAR World Congress of Pharmacology Scientific Program Committee for the 2002 meeting, held in San Francisco, CA. He is also a member of the British Pharmacological Society, the Society for Neuroscience, the AAAS, the American Society for Neurochemistry, and the International Narcotics Research Conference (for which he served as President from 1994-1998).
For most of his career Dr. Cox's research has focused on characterizing the receptors utilized by opiate drugs and their endogenous ligands, and in defining potential physiological and pathophysiological roles for endogenous opioids and other neuropeptides. His lab is currently studying factors affecting peptide and receptor expression, and changes at the cellular level induced by drugs of abuse, severe stress, or neural injury. He now leads the Biomarkers Group of the USU/NIH Center for Neuroscience and Regenerative Medicine, evaluating neurochemical mechanisms underlying traumatic brain injury and potential biomarkers for TBI.
Dr. Cox has been a member of the American Society for Pharmacology and Experimental Therapeutics (ASPET) since 1976. He served as Secretary/Treasurer of (1997-2000), and was elected President of ASPET for 2009-2010. He chaired the ASPET Board of Publications Trustees from 2002-2007. He has served on the Editorial Boards of the Journal of Pharmacology and Experimental Therapeutics (1998 – present), Molecular Pharmacology (1981-1994), and Molecular Interventions (2000-2002). Dr. Cox was a member of the ASPET Scientific Program Committee from 1986-1990 and Chaired the Program Committee from 1990-1996. He served as ASPET’s representative to the Experimental Biology Program Committee from 1991-1994 and served on the Experimental Biology Board from 1996-1999 (as Chairman for 1998-1999). He is currently serving a second term as a member of the Board of Directors of the Federation of American Societies of Experimental Biology.
Dr. Cox was the ASPET representative to the International Advisory Committee for the 1998 International Union of Pharmacology (IUPHAR) Congress in Munich, Germany, and chaired the IUPHAR World Congress of Pharmacology Scientific Program Committee for the 2002 meeting, held in San Francisco, CA. He is also a member of the British Pharmacological Society, the Society for Neuroscience, the AAAS, the American Society for Neurochemistry, and the International Narcotics Research Conference (for which he served as President from 1994-1998).
Representative publications, projects, and/or deployments
- Assistant Dean for Graduate Education, Uniformed Services University, Bethesda MD 20814, since 2014
- Director, Biospecimen Repository, Center for Neuroscience & Regenerative Medicine, Uniformed Services University, Bethesda MD 20814, since 2009
- Professor of Pharmacology, Uniformed Services University, Bethesda MD 20814, since 1981
- Associate Director for Research, Addiction Research Foundation, Stanford, California, 94305, 1977-1981
- Consulting Associate Professor of Pharmacology, Stanford University, Stanford CA, 94305. 1978 - 1981
- Research Associate, Director, Laboratory Research Group, Addiction Research Foundation, Stanford, California, 94305, 1973-1977
- Lecturer (British System) in Pharmacology, Chelsea College, University of London, London, United Kingdom, 1965-1973
- Nicholas Research Fellow, St. Mary's Hospital Medical School, University of London, London, United Kingdom, 1962-1965
Bibliography
- Cox, B.M. and Weinstock, M. Quantitative studies of the antagonism by nalorphine of some of the actions of morphine-like analgesic drugs. Br. J. Pharmac. 22:289-300, 1964.
- Cox, B.M. and Osman, O.H. Inhibition of the development of tolerance to morphine in rats by drugs which inhibit ribonucleic acid or protein synthesis. Br. J. Pharmac. 38:157-170, 1970.
- Cox, B.M., Opheim, K., Teschemacher, H.-J. and Goldstein, A. A peptide-like substance from pituitary that acts like morphine. 2. Purification and properties. Life Sci. 16:1777-1782, 1975.
- Goldstein, A., Cox, B.M., Klee, W.A., and Nirenberg, M. Endorphin from pituitary inhibits cyclic AMP formation in homogenates of neuroblastoma X glioma hybrid cells. Nature 265:362-363, 1977.
- Whitnall, M.H., Gainer, H., Cox, B.M. and Molineaux, C.J. Dynorphin A(1-8) is contained within vasopressin neurosecretory vasicles in rat pituitary. Science 222:1137-1139, 1983.
- Faden, A.I., Molineaux, C.J., Rosenberger, J.G., Jacobs, T.P. and Cox, B.M. Endogenous opioid immunoreactivity in rat spinal cord following traumatic injury. Ann. Neurol. 17:386-390, 1985.
- Werling, L.L., Puttfarcken, P.S. and Cox, B.M. Multiple agonist-affinity states of opioid receptors: regulation of binding by guanyl nucleotides in guinea pig cortical, NG108-15, and 7315c cell membranes. Mol. Pharmacol. 33:423-431, 1988.
- Marti M, Mela F, Fantin M, Zucchini S, Brown JM, Witta J, Di Benedetto M, Buzas B, Reinscheid RK, Salvadori S, Guerrini R, Romualdi P, Candeletti S, Simonato M, Cox BM and Morari M. Blockade of nociceptin/orphanin FQ transmission attenuates symptoms and neurodegeneration associated with Parkinson’s disease. J. Neuroscience 25: 9591-9601, 2005.
- Authement ME, Kodangatil JN, Gouty S, Rusnak M, Symes AJ, Cox BM, Nugent F. Histone deacetylase inhibition rescues maternal deprivation-induced GABAergic metaplasticity through restoration of AKAP signaling. Neuron 86: 1240-1252, 2015.
- Authement M, Kassis H, Langlois L, Gouty S, Dacher M, Sheopard R, Cox BM & Nugent FS. Morphine-induced synaptic abnormalities in the VTA are reversed by HDAC inhibition. J. Neurophysiol. 116(3): 1093-1103, 2016.
Regina M Day, Ph.D.
Name: Regina M Day, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Vice Chair
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Email:
Office Phone:
(301) 295-3236
Education
A.B. Smith College, Northampton, MA, USA
Ph.D. Tufts University, Boston, MA, USA
Ph.D. Tufts University, Boston, MA, USA
Biography
Introduction and overview:
My laboratory is dedicated to understanding normal tissue repair processes and how the repair process is altered in fibrotic remodeling. Normal tissue regeneration for wound healing is a critical focus of research for the military as well as for the medical field in general. The long term goal of my laboratory is to understand the mechanism of fibrotic repair and to identify therapeutic agents to prevent and/or treat this disease. The lung provides an excellent model system for investigation, since it is uniquely sensitive to chemicals and radiation that produce well-defined stages of injury, inflammation, attempted repair, and repair failure/remodeling. Lung fibrosis is a progressive disease with no treatments and poor prognosis. Our laboratory uses in vivo animal models and in vitro primary cell cultures to systematically elucidate the mechanisms of tissue regeneration and fibrotic remodeling at the molecular, biochemical, cellular, and tissue levels.
Radiation countermeasures for the lung and hematopoietic systems and radiation biology:
• Radiation countermeasures for both the hematopoietic and lung tissues. Radiation-induced lung injury is a late effect of radiation, whereas hematopoietic injuries are an acute radiation injury. Because of the Department of Defense’s interest in protection against both acute and delayed injuries, we were requested to develop a murine model for both the hematopoietic and pulmonary injuries, and to test radiation countermeasures in both systems. My laboratory developed an animal model system incorporating both hematopoietic and lung radiation injuries. We have determined the mechanism of action of captopril protection in both tissues, as a part of the requirement for radiation countermeasure development under the Animal Rule for the FDA. We are currently expanding our testing of captopril in the minipig model of radiation acute injuries.
• My laboratory developed a cell culture system for studying the molecular mechanisms of radiation-induced senescence in normal (non-transformed, non-immortalized) cells. Our research demonstrated for the first time that normal lung and skin cells primarily undergo accelerated senescence, and not apoptosis, in response to radiation. We identified an early cellular response to radiation is the induction of insulin-like growth factor 1 (IGF-1) and the activation of its receptor (IGF-1R). These novel and provocative observations prompted us to hypothesize that senescence is the precipitating state for radiation pathology.
Hepatocyte growth factor (HGF) signaling for tissue repair and suppression of fibrosis:
• My laboratory has identified novel signaling pathways for HGF-induced normal tissue repair mechanisms. HGF expression is required for normal tissue repair, and HGF can redirect repair away from fibrotic remodeling to induce normal tissue regrowth. To understand how HGF can accomplish this, my research team investigated signal transduction mechanisms for HGF suppression of apoptosis in epithelial and endothelial cells that is induced during fibrosis. We next investigated the mechanisms by which HGF expression is suppressed during fibrotic remodeling. We recently uncovered a novel mechanism by which miRNA regulates HGF mRNA half-life under fibrotic conditions. This research led to the identification of potential novel anti-fibrotic treatment strategies.
• My laboratory developed a synthetic peptide based on other proteins that bind the HGF receptor, MET. The structural complexity of the full length HGF structure has prevented its development as a pharmaceutical agent, and full length HGF has not been successfully produced in sufficient quantities for clinical use. A patent was submitted by the USU/HJF JOTT based on these findings. Our laboratory currently aims to improve the design of this protein, to improve stability and increase receptor affinity.
My laboratory is dedicated to understanding normal tissue repair processes and how the repair process is altered in fibrotic remodeling. Normal tissue regeneration for wound healing is a critical focus of research for the military as well as for the medical field in general. The long term goal of my laboratory is to understand the mechanism of fibrotic repair and to identify therapeutic agents to prevent and/or treat this disease. The lung provides an excellent model system for investigation, since it is uniquely sensitive to chemicals and radiation that produce well-defined stages of injury, inflammation, attempted repair, and repair failure/remodeling. Lung fibrosis is a progressive disease with no treatments and poor prognosis. Our laboratory uses in vivo animal models and in vitro primary cell cultures to systematically elucidate the mechanisms of tissue regeneration and fibrotic remodeling at the molecular, biochemical, cellular, and tissue levels.
Radiation countermeasures for the lung and hematopoietic systems and radiation biology:
• Radiation countermeasures for both the hematopoietic and lung tissues. Radiation-induced lung injury is a late effect of radiation, whereas hematopoietic injuries are an acute radiation injury. Because of the Department of Defense’s interest in protection against both acute and delayed injuries, we were requested to develop a murine model for both the hematopoietic and pulmonary injuries, and to test radiation countermeasures in both systems. My laboratory developed an animal model system incorporating both hematopoietic and lung radiation injuries. We have determined the mechanism of action of captopril protection in both tissues, as a part of the requirement for radiation countermeasure development under the Animal Rule for the FDA. We are currently expanding our testing of captopril in the minipig model of radiation acute injuries.
• My laboratory developed a cell culture system for studying the molecular mechanisms of radiation-induced senescence in normal (non-transformed, non-immortalized) cells. Our research demonstrated for the first time that normal lung and skin cells primarily undergo accelerated senescence, and not apoptosis, in response to radiation. We identified an early cellular response to radiation is the induction of insulin-like growth factor 1 (IGF-1) and the activation of its receptor (IGF-1R). These novel and provocative observations prompted us to hypothesize that senescence is the precipitating state for radiation pathology.
Hepatocyte growth factor (HGF) signaling for tissue repair and suppression of fibrosis:
• My laboratory has identified novel signaling pathways for HGF-induced normal tissue repair mechanisms. HGF expression is required for normal tissue repair, and HGF can redirect repair away from fibrotic remodeling to induce normal tissue regrowth. To understand how HGF can accomplish this, my research team investigated signal transduction mechanisms for HGF suppression of apoptosis in epithelial and endothelial cells that is induced during fibrosis. We next investigated the mechanisms by which HGF expression is suppressed during fibrotic remodeling. We recently uncovered a novel mechanism by which miRNA regulates HGF mRNA half-life under fibrotic conditions. This research led to the identification of potential novel anti-fibrotic treatment strategies.
• My laboratory developed a synthetic peptide based on other proteins that bind the HGF receptor, MET. The structural complexity of the full length HGF structure has prevented its development as a pharmaceutical agent, and full length HGF has not been successfully produced in sufficient quantities for clinical use. A patent was submitted by the USU/HJF JOTT based on these findings. Our laboratory currently aims to improve the design of this protein, to improve stability and increase receptor affinity.
Representative publications, projects, and/or deployments
- 12/2016 – present Vice Chair USUHS School of Medicine Department of Pharmacology and Molecular Therapeutics
- 7/2014- present Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 11/2014 Adjunct Professor Georgetown University School of Medicine Pulmonary, Critical Care, and Sleep Medicine
- 2/2010- 7/2014 Associate Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 7/2004-1/2010 Tenure Track Assistant Professor USUHS School of Medicine Primary Appointment Department of Pharmacology
- 1/2004-6/2004 Research Assistant Professor Georgetown Univ. School of Medicine Pulmonary, Critical Care, and Sleep Medicine
- 8/1999-12/2004 Research Assistant Professor Tufts-New England Medical Ctr Pulmonary, Critical Care, and Sleep Medicine Div
- Postdoctoral Fellow NIH, NCI, Lab of Cellular, Molecular Biology
Bibliography
- Landauer, M.R., Harvey, A.J., Kaytor, M.D., Day, R.M. (2019) Mechanism and therapeutic window of a genistein nanosuspension to protect against hematopoietic-acute radiation syndrome. J. Radiat. Res. In press.
- McCart, E.A., Lee, Y.H., Jha, J., Mungunsukh, O., Rittase, W.B., Summers, T.A., Muir, J., Day R.M. (2019) Delayed captopril administration mitigates hematopoietic injury in a murine model of total body irradiation. Sci Reports, 9: 2198.
- Bylicky, M.A., Mueller, G.P., Day, R.M. (2019) Radiation resistance of normal human astrocytes: role of non-homologous end joining DNA repair activity. J Radiat Res. 60: 37-50.
- Corey, S.J., Jha, J., McCart, E.A., Rittase, W.B., George, J., Mattapallil, J.J., Mehta, H., Ognoon, M., Bylicky, M.A., Summers, T.A., Day, R.M. (2018) Captopril mitigates splenomegaly and myelofibrosis in the Gata1low murine model of myelofibrosis. J Cell Mol Med, 22: 4274-4282.
- Du, Y., Banas, R.A., McCart, E.A., George, J., Oakley, K., Han, Y., Landauer, M.R., Day, R.M. (2018) Effect of human amnion-derived multipotent progenitor cells on hematopoietic recovery after total body irradiation in C57BL/6 mice. Int J Radiat Res, 16:155-168.
- Zhao*, J., Day*, R.M., Jin, J-Y., Quint, L., Williams, H., Ferguson, C., Yan, L., King, M., Albsheer, A., Matuszak, M., Kong, S-M. (2017) Thoracic radiation-induced pleural effusion and risk factors in patients with lung cancer. Oncotarget, 8: 97623-32.
- McCart, E.A., Lombardini, E., Mog, S.R., Panganiban, R.A.M., Dickson, K.M., Mansur, R.A., Nagy, V., Kim, S-Y., Selwyn, R., Landauer, M.R., Darling, T.N., Day, R.M. (2017) Accelerated senescence in a murine model of radiation-induced skin injury. J Radiat Res, 58: 636-646.
- Brzezniak, C., Oronsky, B., Trepel, J., Summers, T.A. Jr., Cabrales, P., Lee, M.J., Day, R., Jha, S., Caroen, S, Zeman, K, Ferr,y L, Harmer, C, Oronsky, N, Lybeck, M, Lybeck, HE, Brown, JF, Reid, T.R., Carter, C.A. RRx-001 Priming of PD-1 Inhibition in the Treatment of Small Cell Carcinoma of the Vagina: A Rare Gynecological Tumor. Case Rep Oncol. 2017;10:276-280.
- Mungunsukh, O., Lee, Y.H., Bottaro, D.P., Day, R.M. (2016) The hepatocyte growth factor isoform NK2 activates motogenesis and survival but not proliferation due to lack of Akt activation. Cell Signal, 28, 1114-23.
- Barshishat-Kupper, M., McCart E.A., Freedy, J.G., Tipton A.J., Nagy V., Kim, S.-Y., Landauer, M.R., Mueller G.P., Day R.M. (2015) Protein oxidation in the lungs of C57BL/6J mice following X-irradiation. Proteomes, 3, 249-265.
Ying-Hong Feng, M.D., Ph.D
Name: Ying-Hong Feng, M.D., Ph.D
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Dr.
Faculty Rank:
Associate Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Receptor structure-function & signaling; Epigenome editing & transcription regulation
Translational research in neurodegenerative diseases, mood disorder, cancer, diabetes, and cardiovascular diseases
Email:
Office Phone:
(301) 295-3232
Department Website:
Education
1978-1983, M.D., Wuhan University School of Medicine, Wuhan, China
1990-1994, Ph.D., Biochemistry, University of Oxford, Oxford, UK
1994-1997, Postdoctoral, Molecular Cardiology, Cleveland Clinic Foundation
1990-1994, Ph.D., Biochemistry, University of Oxford, Oxford, UK
1994-1997, Postdoctoral, Molecular Cardiology, Cleveland Clinic Foundation
Biography
Feng’s lab has three research programs. The first is about crosstalk signaling of receptors in the form of receptor dimerization in pathophysiology such as vascular inflammation, metabolism (type 2 diabetes), pain (silent myocardial ischemia), depression, immunosuppression, cancer progression, and etc. The second is about translational research on neurodegenerative diseases and cancer with focus on novel splicing variants, of critical genes that are known to play an important role in depression, neurodegeneration, neuroregeneration, exosome biology, tumorigenesis, and cancer progression. The last is to develop novel technologies for genome editing and epigenome editing.
Representative publications, projects, and/or deployments
- Feng YH, Li X, Zeng R, Gorodeski GI. Endogenously Expressed Truncated P2X7 Receptor Lacking the C-Terminus is Preferentially Upregulated in Epithelial Cancer Cells and Fails to Mediate Ligand-Induced Pore Formation and Apoptosis. Nucleosides Nucleotides Nucleic Acids. 25:1271-6 (2006)
- Feng YH, Li X, Zeng R, Gorodeski GI. Endogenously expressed truncated P2X7 receptor lacking the C-terminus is preferentially upregulated in epithelial cancer cells and fails to mediate ligand-induced pore formation and apoptosis. Nucleosides Nucleotides Nucleic Acids. 25(9-11):1271-6 (2006)
- Chen M, Wang T, Liao ZX, Pan XL, Feng YH, Wang H. Nicotine-induced prenatal overexposure to maternal glucocorticoid and intrauterine growth retardation in rat. Exp Toxicol Pathol. 59: 245-51 (2007)
- 30. Zhang X, Wang G, Dupre DJ, Feng Y, Robitaille M, Lazartigues E, Feng YH, Hebert TE, Wu G. Rab1 GTPase and dimerization in the cell surface expression of angiotensin II type 2 receptor. J Pharmacol Exp Ther. 330(1):109-17 (2009)
- 31. Guo J, Li ZC and Feng YH. Expression and activation of the reprogramming transcription factors. Biochem Biophys Res Commun. 390(4):1081-6 (2009)
- 32. Zhang J, Villacorta L, Chang L, Fan Z, Hamblin M, Zhu T, Chen CS, Cole MP, Schopfer FJ, Deng CX, Garcia-Barrio MT, Feng YH, Freeman BA, Chen YE. Nitrated oleic acid inhibits Angiotensin II-induced hypertension. Circ Res, 107(4):540-8 (2010)
- 34. Day RD, Lee YH, Han L, Kim YC, Feng YH. Angiotensin II activates AMPK for execution of apoptosis through energy-dependent and -independent mechanisms. Am J Physiol Lung Cell Mol Physiol, 301(5):L772-81 (2011)
- 35. Wang TT, Chen M, Liu L, Cheng H, Yan YE, Feng YH*, Wang H. Nicotine induces a single CpG methylation in the StAR promoter: a potential mechanism for reduced StAR expression and cortisol production. Toxicol and Applied Pharmacol. 257(3):328-37 (2011) *Co-senior author
- 37. Wang H, Yin H, Yan F, Sun M, Du L, Peng W, Li Q, Feng Y, Zhou Y. Folate-mediated mitochondrial targeting with doxorubicin-polyrotaxane nanoparticles overcomes multidrug resistance. Oncotarget. 6(5):2827-42 (2015).
- 38. Li K, Pang J, Cheng H, Wei-Peng Liu WP, Chen MK, Yun Luo Y, Di JM, Zhang H, Huang WT, Li LY, Shao CK, Feng YH*, Gao X. Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase. Oncotarget. 6(12):10030-44 (2015) *Co-senior author
Bibliography
- Feng YH, Saad Y and Karnik SS. Reversible Inactivation of AT2 Angiotensin II Receptor from Cysteine-Disulfide Bond Exchange. FEBS Letters 484, 133-138 (2000)
- Feng YH, Sun Y, and Douglas JG. G??-Independent Constitutive Association of Gs? with SHP-1 and Angiotensin II Receptor AT2 Is Essential in AT2-mediated Activation of SHP-1. Proc. Natl. Acad. Sci. USA 99:12049-12054 (2002)
- Wang Q, Li X, Wang L, Feng YH, Zeng R, Gorodeski GI. Anti-apoptotic effects of estrogen in normal and in cancer human cervical epithelial cells. Endocrinology 145:5568-79 (2004)
- Wang Q, Wang L, Feng YH, Li X, Zeng R, Gorodeski GI. P2X7-receptor-mediated apoptosis of human cervical epithelial cells. Am J Physiol Cell Physiol. 287:C1349-58 (2004)
- Wang L, Feng YH, Gorodeski GI. EGF facilitates epinephrine inhibition of P2X7-receptor pore formation by modulating 2-adrenoceptor internalization and recycling: a signaling network. Endocrinology 146:164-74 (2005)
- Feng YH, Zhou LY, Sun Y, and Douglas JG. Functional Diversity of AT2 Receptor Orthologues in Closely related Eutherian. Kidney Intl 67:1731-8 (2005)
- eng YH, Wang L, Wang Q, Li X, Zeng R, Gorodeski GI. ATP ligation stimulates GRK-3 - mediated phosphorylation and -arrestin-2- and dynamin-dependent internalization of the P2X7-receptor. Am J Physiol Cell Physiol. 288:C1342-56 (2005)
- Feng YH, Zhou L, Qiu R, and Robin Zeng. Single mutations at Asn295 and Leu305 in the cytoplasmic half of TM7 of the AT1 receptor induce promiscuous agonist specificity for angiotensin II fragments - A PSEUDO-CONSTITUTIVE ACTIVITY. Mol Pharmacol 68:347-55 (2005)
- Feng YH, Ding Y, Ren S, Xu C, Karnik SS. Unconventional homologous internalization of the AT1 receptor induced by G protein-independent signals. Hypertension 46:419-25 (2005)
- Feng YH, Li X, Wang L, Zhou L, Gorodeski GI. A truncated P2X7 receptor variant (P2X7-j) endogenously expressed in cervical cancer cells antagonizes the full-length P2X7 receptor through hetero-oligomerization. J Biol Chem. 281:17228-37 (2006)
Sergey Iordanskiy, Ph.D.
Name: Sergey Iordanskiy, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Assistant Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Molecular biology of retroviruses & retroelements; Effect of radiation-induced cellular stress on virus latency, replication and cellular response; Exosomes in intercellular communication and cytopathogenesis.
Lentiviral vectors for delivery and expression of genome editing tools; Coinfection of HIV and human blood parasites.
Email:
Office Phone:
(301) 295-0580
Department Website:
Education
B.S & M.S., Biochemistry, Moscow State University of Education, Moscow, Russia
Ph.D., Cellular Biology, Moscow State University of Education & Ivanovsky Research Institute of Virology, Russian Academy of Medical Sciences
Postdoctoral Training, Molecular Biology of AIDS, Picower Institute for Medical Research, Manhasset, NY
Postdoctoral Training, Molecular Virology, George Washington University, Washington, DC
Ph.D., Cellular Biology, Moscow State University of Education & Ivanovsky Research Institute of Virology, Russian Academy of Medical Sciences
Postdoctoral Training, Molecular Biology of AIDS, Picower Institute for Medical Research, Manhasset, NY
Postdoctoral Training, Molecular Virology, George Washington University, Washington, DC
Biography
RESEARCH DESCRIPTION:
My laboratory studies the molecular mechanisms of innate immune response to radiation-induced stress and involvement of the endogenous retroviruses and retroelements in this response. Even mild radiation doses may induce prolonged or chronic inflammation that disrupts organ functions. This is an important factor of secondary radiation-related disorders, such as vascular abnormalities, neuronal damage, autoimmune diseases and radiation-related cancer. We consider molecular patterns associated with viral infections, such as viral RNAs and proteins as the essential factors that modulate and exacerbate radiation-induced inflammation.
Ongoing Projects:
Radiation-induced cellular stress and human endogenous retroviruses
Human endogenous retroviruses (HERVs) constitute 8.3% of our genome. Most of integrated HERV genomes are silenced. However, detection of high levels of HERV-K mRNA, proteins, and even viral particles in a wide range of embryonic cells and cancers suggests that some HERVs may play an essential role in cell differentiation and cancer development. Recent studies revealed transcriptional activation of some retroviral genomes in various cancers and immune cells after exposure to radiation doses. We investigate the effect of gamma radiation on the expression of human endogenous retroviruses and their impact on inflammatory response in various types of immune cells. We found that promoters of certain HERV genomes become permanently activated after the single doses of radiation. Retroviral RNA, as well as some viral proteins, particularly Env (envelope protein), affect innate immune response and can enhance radiation-induced inflammation via the activation of critical pathways. Our ultimate goal is to elucidate the retrovirus-related mechanisms that enhance radiation-induced inflammation and indirect pathogenic effect of radiation on unexposed cells. Our long term goal is to reduce the inflammatory response to ionizing radiation using reprogramming cytokine profile of radiation-activated cells from pro- to anti-inflammatory phenotype via the modulation of expression of endogenous retroelements.
Exosomes in cytopathogenesis and intercellular communications within context of radiation-induced stress.
Initially small extracellular vesicles, exosomes, were thought to be a mechanism for discarding unwanted cellular material. However, in recent years, numerous evidence has indicated the role of exosomes in intercellular communication and the progression of various pathologies, including cancer and multiple neurodegenerative disorders. Exosomes are cell-derived vesicles that are present in all biological fluids and are capable of carrying RNAs and proteins which can be exchanged from cell-to-cell. Existing data indicate that exosomes and their cargo play crucial roles in communicating of radiation-induced and bystander cells with the result related to DNA damage and cell pathogenesis. We recently demonstrated multiple pathogenic effects of exosomes from the cells containing integrated retroviral genomes, such as human T lymphotropic virus 1 (HTLV-1) and HIV-1 on naïve cells. These effects were enhanced by the exposure of producing cells to ionizing radiation. Current research in our laboratory is focused on the analysis of host-cellular and viral cargo in the exosomes released from the radiation-exposed cells. We also investigate how non radiation-exposed cells respond to exosome-mediated effect of radiation in the context of radiotherapy and environmental radiation. Potential outcomes include understanding of the functions of exosome-packaged noncoding RNAs and mRNA, viral and host proteins in recipient cells and their pathogenic impact that is related to radiation. Identification of exosome-incorporated biomarkers of radiation doses is also part of this study.
Collaborative Projects
Our laboratory is involved in collaborative projects with George Washington University (Paul Brindley Lab) and Massachusetts Institute of Technology (Kevin Esvelt Lab). These studies are related to coinfection of HIV and human blood fluke Schistosoma mansoni and S. hematobium and the use of HIV-based lentiviral vectors for delivery of gene editing tools within the context of Gene Drive strategy.
My laboratory studies the molecular mechanisms of innate immune response to radiation-induced stress and involvement of the endogenous retroviruses and retroelements in this response. Even mild radiation doses may induce prolonged or chronic inflammation that disrupts organ functions. This is an important factor of secondary radiation-related disorders, such as vascular abnormalities, neuronal damage, autoimmune diseases and radiation-related cancer. We consider molecular patterns associated with viral infections, such as viral RNAs and proteins as the essential factors that modulate and exacerbate radiation-induced inflammation.
Ongoing Projects:
Radiation-induced cellular stress and human endogenous retroviruses
Human endogenous retroviruses (HERVs) constitute 8.3% of our genome. Most of integrated HERV genomes are silenced. However, detection of high levels of HERV-K mRNA, proteins, and even viral particles in a wide range of embryonic cells and cancers suggests that some HERVs may play an essential role in cell differentiation and cancer development. Recent studies revealed transcriptional activation of some retroviral genomes in various cancers and immune cells after exposure to radiation doses. We investigate the effect of gamma radiation on the expression of human endogenous retroviruses and their impact on inflammatory response in various types of immune cells. We found that promoters of certain HERV genomes become permanently activated after the single doses of radiation. Retroviral RNA, as well as some viral proteins, particularly Env (envelope protein), affect innate immune response and can enhance radiation-induced inflammation via the activation of critical pathways. Our ultimate goal is to elucidate the retrovirus-related mechanisms that enhance radiation-induced inflammation and indirect pathogenic effect of radiation on unexposed cells. Our long term goal is to reduce the inflammatory response to ionizing radiation using reprogramming cytokine profile of radiation-activated cells from pro- to anti-inflammatory phenotype via the modulation of expression of endogenous retroelements.
Exosomes in cytopathogenesis and intercellular communications within context of radiation-induced stress.
Initially small extracellular vesicles, exosomes, were thought to be a mechanism for discarding unwanted cellular material. However, in recent years, numerous evidence has indicated the role of exosomes in intercellular communication and the progression of various pathologies, including cancer and multiple neurodegenerative disorders. Exosomes are cell-derived vesicles that are present in all biological fluids and are capable of carrying RNAs and proteins which can be exchanged from cell-to-cell. Existing data indicate that exosomes and their cargo play crucial roles in communicating of radiation-induced and bystander cells with the result related to DNA damage and cell pathogenesis. We recently demonstrated multiple pathogenic effects of exosomes from the cells containing integrated retroviral genomes, such as human T lymphotropic virus 1 (HTLV-1) and HIV-1 on naïve cells. These effects were enhanced by the exposure of producing cells to ionizing radiation. Current research in our laboratory is focused on the analysis of host-cellular and viral cargo in the exosomes released from the radiation-exposed cells. We also investigate how non radiation-exposed cells respond to exosome-mediated effect of radiation in the context of radiotherapy and environmental radiation. Potential outcomes include understanding of the functions of exosome-packaged noncoding RNAs and mRNA, viral and host proteins in recipient cells and their pathogenic impact that is related to radiation. Identification of exosome-incorporated biomarkers of radiation doses is also part of this study.
Collaborative Projects
Our laboratory is involved in collaborative projects with George Washington University (Paul Brindley Lab) and Massachusetts Institute of Technology (Kevin Esvelt Lab). These studies are related to coinfection of HIV and human blood fluke Schistosoma mansoni and S. hematobium and the use of HIV-based lentiviral vectors for delivery of gene editing tools within the context of Gene Drive strategy.
Representative publications, projects, and/or deployments
- Barclay RA, Schwab A, DeMarino C, Akpamagbo Y, Lepene B, Kassaye S, Iordanskiy S and F. Kashanchi. Exosomes from uninfected cells activate transcription of latent HIV-1. J Biol Chem. 2017 292(28):11682-11701; PMID: 28536264
- Akpamagbo YA, DeMarino C, Pleet ML, Schwab A, Rodriguez M, Barclay RA, Sampey G, Iordanskiy S, El-Hage N and F Kashanchi. HIV-1 Transcription Inhibitors Increase the Synthesis of Viral Non-Coding RNA that Contribute to Latency. Curr Pharm Des. 2017; 23(28):4133-4144. PMID: 28641535.
- Pleet ML, Mathiesen A, DeMarino C, Akpamagbo YA, Barclay RA, Schwab A, Iordanskiy S, Sampey GC, Lepene B, Nekhai S, Aman MJ and F Kashanchi. Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction. Front Microbiol. 2018; 9:692.. PMID: 29696006.
Bibliography
Biosketch Link:
- Suttiprapa S, Rinaldi G, Tsai IJ, Mann VH, Dubrovsky L, Yan HB, Holroyd N, Huckvale T, Durrant C, Protasio AV, Pushkarsky T, Iordanskiy S, Berriman M, Bukrinsky MI and PJ Brindley, HIV-1 Integrates Widely throughout the Genome of the Human Blood Fluke Schistosoma mansoni. PLoS Pathog. 2016 Oct 20;12(10):e1005931.
- Santos S, Obukhov Y, Nekhai S, Pushkarsky T, Brichacek B, Bukrinsky M and S Iordanskiy. Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells, Virology. 2016 Oct;497:11-22.
- Iordanskiy S and F Kashanchi, Potential of radiation-induced cellular stress for reactivation of latent HIV-1 and killing of infected cells. AIDS Res Hum Retroviruses. 2016 32(2):120-124.
- Sampey G, Saifuddin M, Schwab A, Barclay R, Punya S, Chung M-Y, Hakami RM, Asad Zadeh M, Lepene B, Klase ZA, El-Hage N, Young M, Iordanskiy S and F Kashanchi, Exosomes from HIV-1 infected cells stimulate production of pro-inflammatory cytokines through TAR RNA. J Biol Chem. 2016 291(3):1251-1266.
- Iordanskiy S, Van Duyne R, Sampey GC, Woodson CM, Fry K, Saifuddin M, Guo J, Wu Y, Romerio F and F Kashanchi, Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells. Virology 2015, 485:1–15.
- Guendel I, Iordanskiy S, Van Duyne R, Kehn-Hall K, Saifuddin M, Das R, Jaworski E, Sampey G, Senina S, Shultz L, Narayanan A, Chen H, Lepene B, Zeng C, and F. Kashanchi, Novel neuroprotective GSK-3β inhibitor restricts Tat-mediated HIV-1 replication. J Virol 2014, 88(2): 1189-1208
- Narayanan A, Iordanskiy S, Das R, Van Duyne R, Santos S, Jaworski E, Guendel I, Sampey G, Gerhart E, Iglesias-Ussel M, Popratiloff A, Hakami R, Kehn-Hall K, Young M, Subra C, Gilbert C, Bailey C, Romerio F and F. Kashanchi, Exosomes derived from HIV-1 infected cells contain TAR RNA. J Biol Chem. 2013 288(27): 20014-20033.
- Santos S, Obukhov Y, Nekhai S, Bukrinsky M and S Iordanskiy, Virus-producing cells determine the host protein profiles of HIV-1 virion cores. Retrovirology. 2012, 9:65.
- Iordanskiy S, Berro R, Altieri M, Kashanchi F. and M. Bukrinsky, Intracytoplasmic maturation of the human immunodeficiency virus type 1 reverse transcription complexes determines their capacity to integrate into chromatin. Retrovirology 2006. 3: 4
- Iordanskiy S, Zhao Y, DiMarzio P, Agostini I, Dubrovsky L, and M. Bukrinsky, Heat-shock protein 70 exerts opposing effects on Vpr-dependent and Vpr-independent HIV-1 replication in macrophages. Blood. 2004. 104: 1867-1872.
Juliann G. Kiang, M.A., Ph.D.
Name: Juliann G. Kiang, M.A., Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Adjunct Professor
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Molecular mechanism underlying Radiation and drug development for radiation combined injury
Polytrauma Injury
Email:
Office Phone:
(301) 295-1076
Department Website:
Education
Postdoctoral, University of California, Berkeley, CA 1984-1988
Ph.D. University of California, Berkeley, CA, 1983
M.A. University of Nebraska, Omaha, NE, 1977
B.S. FuJen Catholic University, Taipei, Taiwan, ROC, 1975
Ph.D. University of California, Berkeley, CA, 1983
M.A. University of Nebraska, Omaha, NE, 1977
B.S. FuJen Catholic University, Taipei, Taiwan, ROC, 1975
Biography
Dr. Juliann Kiang is a principal investigator at Armed Forces Radiobiology Research Institute (AFRRI). She is Adjunct Professor in Department of Pharmacology and Molecular Therapeutics and in Department of Medicine, School of Medicine, Uniformed Services University of the Health Sciences (USU).
Dr. Kiang serves in editorial boards of several scientific journals, NIH and VA study sections, and USU committees. She worked in Water Reed Army Institute of Research from 1989 to 2006 before joining AFRRI.
Dr. Kiang is involved in studies showing corticotrophin-releasing factor and heat shock proteins are capable of protecting against edema/inflammation and hypoxia injury, respectively. She demonstrates that overexpression of inducible form of heat shock protein 70 kDa induced by sublethal heat stress, chemical stimulation, or the gene transfer produces thermotolerance and cross-tolerance that may be related to an inhibition of changes in intracellular calcium concentrations and expression of stress-related genes and proteins such as inducible nitric oxide synthase and p38-MAPK. She has found 17-DMAG, mesenchymal stem cells, G-CSF, ghrelin, or ciprofloxacin that can make cells endure much better under circumstances of low oxygen, a way to treat heat stroke, ischemia, hemorrhage, cancer, heart attack, stroke, or ionizing radiation injury.
Dr. Kiang had made four major contributions in her research career (journal references to work are noted).
Dr. Kiang is the first to demonstrate that treatment with corticotrophin-releasing factor (CRF) inhibits neurogenic and thermally-induced protein extravasation in rats (9-14). She also found that urotensin I and sauvagine (members of the CRF superfamily) possess the same properties as CRF but with greater potency (15). She holds a patent resulting from this work. She has provided evidence that CRF and its analogs increase intracellular Ca2+ concentrations in vitro (33, 36, 50), which are correlated with capacity of these neuropeptides to inhibit thermally-induced edema (50). CRF exerts its action on CRF type 2 receptors to activate enzymes such as tyrosine kinases, phospholipase 1 and 2 to lead to a result of increases in intracellular Ca2+ concentrations (56). A patent is resulted.
Dr. Kiang’s second major contribution is that she performed extensive research to establish the effect of heat shock on components of signal transduction pathways, such as H+, Ca2+, Na+, cAMP, inositol 1,4,5-trisphosphate, and heat shock proteins in cultured cells. Her findings in this area are wide-ranging and have extended knowledge in the heat shock field (18, 19, 22, 25, 29, 40-42, 44, 46-48, 51-55, 57, 58, 60-62). Her findings provide insight to unfold the mechanisms of tolerance and cross-tolerance (64, 67). Heat shock protein 70 kDa plays a very important role in cell survival – a fine-line before occurrence of apoptosis.
Dr. Kiang’s third major contribution is that she has shown heat shock protein 70 kDa (HSP-70i) can protect the rat ileum from the ischemia/reperfusion injury (37, 66), ricin injury (47), during ileitis (57), and the mouse jejunum, lung, heart, and kidney from the hemorrhagic shock (70). She has also shown that down-regulation of inducible nitric oxide synthase inhibits the activity of caspase-3, an apoptotic protease, and overexpression of HSP-70i prevents ATP loss resulted from hemorrhage (78, 87, 91, 99, 104) or radiation-injury (106-108, 110-114). The work has resulted in a provisional patent.
Dr. Kiang’s fourth major contribution is that she has characterized radiation combined injury (110, 111, 115, 120) shown that ciprofloxacin (122, 126-128, 134), ghrelin (130, 146), and bone marrow mesenchymal stem cells (132, 140) can combat radiation injury combined with skin-wound injury. The research work is ongoing. Meanwhile, she established a new combined injury model of radiation with hemorrhage (135, 138, 142, 145) that brought her the 2016 AFRRI Research Award.
Bubliography
Peer-reviewed publications (149)
1. Kiang JG, Dewey WL, and Wei ET. Tolerance to morphine bradycardia in the rat. J. Pharmacol Exp. Ther. 226:187 192, 1983.
2. Kiang JG and Wei ET. Inhibition of an opiate-induced vagal reflex in rats by naloxone, SMS 201 995 and ICI 154, 129. Regulatory Peptides 6:255 262, 1983.
3. Dashwood MR, Kiang JG, and Wei ET. An etorphine-evoked reflex in rats is inhibited by naloxone, N-methylnaloxone, and SMS 201 995. Arch. Int. Pharmacodyn. Ther. 266:77 82, 1983.
4. Kiang JG and Wei ET. Sensitivity to morphine-evoked bradycardia in rats is modified by dynorphin (1 13), (Leu)enkephalin and (Met)enkephalin. J. Pharmacol. Exp. Ther. 229:469 473, 1984.
5. Kiang JG and Wei ET. Peripheral opioid receptors influencing heart rate in rats: evidence for endogenous tolerance. Regulatory Peptides 8:297 303, 1984.
6. Tang J, Webber RJ, Chang D, Chang JK, Kiang JG, and Wei ET. Depressor and natriuretic activities of several atrial peptides. Regulatory Peptides 9:543 549, 1984.
7. Wei ET and Kiang JG. Peripheral opioid receptors influencing heart rate in rats. In: Opioid Peptides in the Periphery. (Eds, F. Fraioli, A. Isidori and M. Mazzetti) Developments in Neuroscience 18:95 101, 1984, Amsterdam, Elsevier.
8. Kiang JG and Wei ET. CRF-evoked bradycardia in urethane-anesthetized rats is blocked by naloxone. Peptides 6:409 413, 1985.
9. Kiang JG and Wei ET. CRF: an inhibitor of neurogenic plasma extravasation produced by saphenous nerve stimulation. Eur. J. Pharmacol. 114:111 112, 1985.
10. Wei ET, Kiang JG, Buchan P, and Smith T. Corticotropin-releasing factor (CRF) inhibits neurogenic plasma extravasation in the rat paw. J. Pharmacol. Exp. Ther. 238:783 787, 1986.
11. Kiang JG and Wei ET. Corticotropin-releasing factor (CRF) inhibits thermal injury. J. Pharmacol. Exp. Ther. 243:517- 520, 1987.
12. Wei ET and Kiang JG. Inhibition of protein exudation from the trachea by corticotropin-releasing factor. Eur. J. Pharmacol. 140:63-67, 1987.
13. Wei ET, Kiang JG, and Tien JQ. Anti-inflammatory activity of corticotropin-releasing factor: I. Efficacy studies. Proc. West. Pharmacol. Soc. 30:59 62, 1987.
14. Kiang JG, Poree L, and Wei ET. Anti-inflammatory activity of corticotropin-releasing factor: II. Mechanisms of action. Proc. West. Pharmacol. Soc. 30:63 65, 1987.
15. Wei ET and Kiang JG. Peptides of the corticoliberin superfamily attenuate thermal and neurogenic inflammation in rat paw skin. Eur. J. Pharmacol. 168:81 86, 1989.
16. Kiang JG and Colden-Stanfield M. Morphine induces an intracellular alkalinization in bovine aortic endothelial cells (BAECs), In: International Narcotic Research Conference (INRC) '89. (Eds. R. Quirion, K. Jhamandas and C. Gianoulakis) Alan Liss Press, N.Y., Prog. Clin. Biol. Res. 328:137 140, 1989.
17. Wei ET, Wong JC, and Kiang JG. Decreased inflammatory responsiveness of hypophysectomized rats to heat is reversed by a CRF antagonist. Regulatory Peptides 27:317 323, 1990.
18. Kiang JG, McKinney LC, and Gallin EK. Heat induces an intracellular acidification in human A 431 cells: role of Na+/H+ exchanger and metabolism. Am. J. Physiol., 259(Cell Physiol. 28):C727-C737, 1990.
19. Kiang JG, Wu YY, and Lin M. Hyperthermia elevates cAMP levels in human epidermoid A 431 cells. Biochem. J. 276:683 689, 1991.
20. Kiang JG. Effect of intracellular pH on cytosolic free [Ca2+]i in A-431 cells. Eur. J. Pharmacol. 207(Molecular Pharmacol. Section):287-296, 1991.
21. Lin W-W, Kiang JG, and Chuang D-M. Pharmacological characterization of endothelin-stimulated phosphoinositides breakdown and cytosolic Ca2+ rise in C6 rat glioma cells. J. Neurosci., 12:1077 1085, 1992.
22. Kiang JG, Koenig ML, and Smallridge RC. Heat shock increases cytosolic free Ca2+ concentration via the Na+/Ca2+ exchange in human epidermoid A 431 cells. Am. J. Physiol. 263(Cell Physiol. 32):C30-38, 1992.
23. Smallridge RC, Gist ID, and Kiang JG. Na+-H+ antiport and monensin effects on cytosolic pH and iodide transport in FRTL 5 rat thyroid cells. Am. J. Physiol. 262(Endocrinol. Metab.) 25:E834-E839, 1992.
24. Smallridge RC, Kiang JG, Gist ID, Fein HG, and Galloway R. U 72133 inhibits TRH-induced activities in GH3 cells. Endocrinol. 131:1883 1888, 1992.
25. Kiang JG and McClain DE. Effect of heat shock, Ca2+, and cAMP on inositol 1,4,5-trisphosphate in human epidermoid A 431 cells. Am. J. Physiol. 264 (Cell Physiol. 33):C1561-C1569, 1993.
26. Aloj SM, Liguoro D, Kiang JG, and Smallridge RC. Purinergic (P2) receptor -operated calcium entry into rat thyroid cells. Biophy. Biochim. Res. Comm. 195:1-7, 1993.
27. Kiang JG. Corticotropin-releasing factor increases cytosolic free calcium via receptor-mediated Ca2+ channels. Eur. J. Pharmacol. (Molecular Pharmacol. Section) 267:135-142, 1994.
28. Kiang JG and Smallridge RC. Sodium cyanide increases cytosolic free calcium: Evidence of activation of the reversed mode of Na+/Ca2+ exchanger and Ca2+ mobilization from inositol trisphosphate-insensitive pools. Toxicol. Appl. Pharmacol., 127:173-181, 1994.
29. Kiang JG, Carr FE, Burns MR, and McClain DE. HSP-72 synthesis is promoted by increase in [Ca2+]i or activation of G proteins but not pHi or cAMP. Am. J. Physiol. 267 (Cell Physiol. 36):C104-C114, 1994.
30. Tang T, Kiang JG, and Cox BM. Opioids acting through delta-receptors increase the intracellular free calcium concentration in the dorsal root ganglion neuroblastoma hybrid ND8-47 cells. J. Pharmacol. Exptl. Ther., 270:40-46, 1994.
31. Wang X, Kiang JG, and Smallridge RC. U-73122 inhibits increases in inositol trisphosphates and cytosolic free [Ca2+] induced by TSH in FRTL-5 cells. Bioph. Biochim. Acta, 1223:101-106, 1994.
32. Poola I and Kiang JG. The estrogen inducible transferrin receptor-like membrane glycoprotein is related to stress regulated proteins. J. Biol. Chem. 269:1-8, 1994.
33. Kiang JG, Wang XD, and McClain DE. Corticotropin-releasing factor increases protein kinase C activity by elevating isoforms and at the membrane. Chin J. Physiol. 37:105-110, 1994.
34. Wang XD, Kiang JG, and Smallridge RC. Identification of protein kinase C and its multiple isoforms in Frtl-5 thyroid cells. Thyroid 5:137-140, 1995.
35. Tang T, Kiang JG, Cote T, and Cox BM. Opioid-induced increase [Ca2+]i in ND8-47 neuroblastoma X DRG hybrid cells is mediated through G protein-coupled delta opioid receptors and desensitized by chronic exposure to opioid. J. Neurochem. 65:1612-1621, 1995.
36. Kiang JG. Mystixin-7 and Mystixin-11 increase [Ca2+]i and inositol trisphosphates in human A-431 cells. Eur. J. Pharmacol. (Mol. Pharmacol. Section) 291:107-113, 1995.
37. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Heat shock protein 72 kD induction protects rat intestinal mucosa from ischemia/reperfusion injury. Gastroenterol. 109:505-515, 1995.
38. Tang T, Kiang JG, Cote T, and Cox BM. Antisense oligodeoxynucleotide to Gái2 protein á-subunit sequence inhibits an opioid-induced increase in intracellular free calcium in ND8-47 neuroblastoma x DRG hybrid cells. Mol. Pharmacol. 48:189-193, 1995.
39. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Rapid assay of HSF1 and HSF2 gene expression by reverse transcriptase PCR. Mol. Cell Biochem. 158: 48-51, 1996.
40. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Increases in HSF1 translocation and synthesis in human epidermoid A-431 cells: role of protein kinase C and [Ca2+]i. J. Investig. Med. 44:144-153, 1996.
41. Kiang JG, Ding XZ, and McClain DE. Thermotolerance attenuates heat-induced increases in [Ca2+]i and HSP-72 synthesis but not heat-induced intracellular acidification in human A-431 cells. J. Investig. Med. 44:189-192, 1996.
42. Kiang JG, Wang XD, Ding XZ, Gist I, and Smallridge RC. Heat shock inhibits the hypoxia-induced effects on iodide uptake and signal transduction and enhances cell survival in rat thyroid FRTL-5 cells. Thyroid, 6:475-483, 1996.
43. Wang XD, Kiang JG, Atwa MA, and Smallridge RC. Evidence for the involvement of protein kinase C isoforms in á-1 adrenergic activation of phospholipase A2 in Frtl-5 thyroid cells, J. Investig. Med. 44:566-574, 1996.
44. Kiang JG and Koenig ML. Characterization of intracellular calcium pools in thermotolerant and their desensitization in thermotolerant cells. J. Investig. Med. 44:352-361, 1996.
45. Kiang JG and Tsokos GC. Signal transduction and heat shock protein expression. J. Biomed. Sci. 3:379-388, 1996.
46. Ding XZ, Tsokos GC, Smallridge RC, and Kiang JG. Heat shock gene expression in HSP-70 and HSF1 gene-transfected human epidermoid A-431 cells. Mol. Cell. Biochem. 167:145-152, 1997.
47. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Induction of the heat shock response limits tissue injury during acute inflammation of the rat ileum. Critical Care Medicine 25:309-317, 1997.
48. Ding XZ, Tsokos GC, and Kiang JG. Heat shock factor 1 protein in heat shock factor 1 gene-transfected human epidermoid A-431 cells requires phosphorylation prior to inducing heat shock protein-70 production. J. Clin. Investig. 99:136-143, 1997.
49. Liossis S-N, Ding XZ, Kiang JG, and Tsokos GC. Overexpression of HSP70 offers thermoprotection but enhances the TCR/CD3- and Fas-induced apoptotic death in Jurkat T-cells. J. Immunol. 158:5668-5675, 1997.
50. Kiang JG. Corticotropin-releasing factor-like peptides increase cytosolic free calcium in human epidermoid A-431 cells. Eur. J. Pharmacol. (Molecular Pharmacology Section), 329:237-244, 1997.
51. Kiang JG, Gist ID, and Tsokos GC. 17-Estradiol-induced increases in glucose-regulated proteins protect human breast cancer T47-D cells from thermal injury. Chin. J. Physiol. 40:213-219, 1997.
52. Kiang JG, Ding XZ, and McClain DE. Overexpression of HSP-70 attenuates increases in [Ca2+]i and protects human epidermoid A-431 cells after chemical hypoxia. Toxicol. Appl. Pharmacol. 149:185-194, 1998.
53. Ding XZ, Tsokos GC, and Kiang JG. Overexpression of HSP-70 inhibits the phosphorylation of HSF1 by activating protein phosphatase and inhibiting protein kinase C activity. FASEB. J. 12:451-459, 1998.
54. Kiang JG, Gist ID, and Tsokos GC. Cytoprotection and regulation of heat shock proteins induced by heat shock in human breast cancer T47-D cells: role of [Ca2+]i and protein kinases. FASEB J. 12: 1571-1579, 1998.
55. Kiang JG and Tsokos GC. Heat shock protein 70 kD family: Molecular Biology, Biochemistry, and Physiology. Pharmacol.Ther. 80:183-201, 1998.
56. Kiang JG, Ding XZ, Gist ID, and Tsokos GC. Corticotropin-releasing factor increases phosphotyrosine of phospholipase C- at tyrosine residues via its receptor 2 in human epidermoid A-431 cells. Eur. J. Pharmacol. 363:203-210, 1998.
57. Goldhill JM, Stojadinovic A, KiangJG, Smallridge RC, and Shea-Donohue T. Hyperthermia prevents functional, histological and biochemical abnormalities induced during ileitis. Neurogastroenterol. Mot. 11:69-76, 1999.
58. Kiang JG, Gist ID, and Tsokos GC. Biochemical requirement of heat shock protein 72 kD expression in human breast cancer MCF-7 cells. Mol. Cell. Biochem.199: 179-188, 1999.
59. Wang XD, Kiang JG, Scheibel LW, and Smallridge RC. Phospholipase C activation by Na+/Ca2+ exchange is essential for monensin-induced Ca2+ influx and arachidonic release in FRTL-5 thyroid cells. J. Investig. Med., 47:388-396, 1999.
60. Kiang JG and McClain DE. N-nitro-L-arginine decreases resting cytosolic [Ca2+] and enhances heat stress-induced increase in cytosolic [Ca2+] in human colon carcinoma T84 cells. Chin. J. Physiol. 42: 153-160, 1999.
61. Smallridge RC, Gist ID, Tsokos GC, and Kiang JG. Characterization of distinct heat shock and thapsigargin-induced cytoprotective proteins in FRTL-5 cells. Thyroid, 9: 1041-1047, 1999.
62. Kiang JG, Gist ID, and Tsokos GC. Heat shock induces expression of heat shock protein 72 kD and 90 kD in human breast cancer MDA-231 cells. Mol. Cell. Biochem. 204: 169-178, 2000.
63. Kiang JC and Lu PY. Biological effects of qigong and an overview of research design and methodology. Proceedings: The Science and Spirituality of Healing, 1: 99-121, 2000.
64. Kiang JG, Kiang SC, Juang Y-T, and Tsokos GC. Nω-nitro-L-arginine inhibits the inducible heat shock protein 70 kDa via Ca2+, PKC, and PKA. Am. J. Physiol. 282:G415-G423, 2002.
65. Kiang JG, Marotta D, Wirkus M, Wirkus M, and Jonas WB. External bioenergy increases intracellular free calcium concentrations and reduces cellular response to heat stress. J. Investig. Med., 50: 38-45, 2002.
66. Fleming SD, Starnes BW, Kiang JG, Stojadinovic A, Tsokos GC, and Shea-Donohue T. Heat stress protection against mesenteric ischemia/reperfusion-induced alteration in intestinal mucosa in rats. J. Appl. Physiol. 92:2600-2607, 2002.
67. Kiang JG. Genistein inhibits herbimycin A-induced inducible heat shock protein 70 kDa. Mol Cell Biochem, 245:191-199, 2003.
68. Kiang JG, McClain DE, Warke VG, Krishnan S, and Tsokos GC. Constitutive NO synthase regulates the Na+/Ca2+ exchanger in human Jurkat T cells: role of [Ca2+]i and tyrosine phosphorylation. J. Cellular Biochem., 89:1030-1043, 2003.
69. Kiang JG, Warke VG, and Tsokos GC. NaCN-induced chemical hypoxia is associated with altered gene expression. Mol Cell Biochem 254:211-216, 2003.
70. Kiang JG, Bowman DP, Wu BW, Hampton N, Kiang AG, Zhao B, Juang Y-T, Atkins JL, and Tsokos GC. Geldanmaycin inhibits hemorrhage-induced increases in caspase-3 activity, KLF6, and iNOS expression in unresuscitated organs of mice: Role of inducible HSP-70. J Appl Phsiol 97:564-569, 2004.
71. Kiang JG, Bowman PD, Zhao B, Atkins JL, and Tsokos GC. Heat shock protein-70 inducers and iNOS inhibitors as therapeutics to ameliorate hemorrhagic shock. NATO-HFM-109-P28:1-11, 2004.
72. Fleming SD, Kiang JG, and Tsokos GC. Targeting complement in treatment of ischemia/reperfusion-induced injury. NATO-HFM-109-P24:1-13, 2004.
73. Bowman PD, Zhao B, Bynum JA, Sondeen JL, Kiang JG, Dubick MA, and Atkins JL. Application of gene expression analysis with microarrays and proteinomics to the problem of hemorrhagic shock and resuscitation. NATO-HFM-109-P29:1-15, 2004.
74. Kiang JG. Inducible heat shock protein 70 kD and inducible nitric oxide synthase in hemorrhage/resuscitation-induced injury. Cell Res 14:450-459, 2004.
75. Kiang JG, Ives JH, and Jonas WB. External bioenergy-induced increases in intracellular free calcium concentrations are mediated by the Na+/Ca2+ exchanger and L-type calcium channel. Mol Cell Biochem 271:51-59, 2005.
76. Kiang JG. Lu X, Tabaku LS, Bentley TB, Atkins JL, and Tsokos GC. Resuscitation with lactated Ringers solution limits the expression of molecular events associated with lung injury after hemorrhage. J Appl Physiol 98:550-556, 2005.
77. Krishnan S, Kiang JG, Fisher CU, Nambiar MP, Nguyen HT, Kyttaris VC, Chowdhury B, Rus V, Tsokos GC. Increased caspase-3 expression and activity contributes to reduced CD3 expression in Systemic Lupus Erythematosus T cells. J Immunol 175:3417-3423, 2005.
78. Kiang JG, Bowman DP, Lu X, Li Yansong, Ding XZ, Zhao B, Juang YT, Atkins JL, Tsokos GC. Geldanmaycin treatment prevents hemorrhage-induced ATP loss in mouse organs by overexpressing HSP-70 and activating pyruvate dehydrogenase. Am J Physiol 291:G117-G127, 2006.
79. Tsen KT, Tsen SWD, Kiang JG. Lycopene is more potent than bata carotene in the neutralization of singlet oxygen: role of energy transfer probed by ultrafast Raman spectroscopy. J Biomed Optics 11:064025 (6 pages), 2006.
80. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN: Dependence on the injected carrier density. App Physics Lett 89:11211 (3 pages), 2006.
81. Tsen KT, Kiang JG, Ferry DK, Kochelap VA, Komirenko SM, Kim KW, Morkoc H. Subpicosecond Raman studies of electric-field-induced optical phonon instability in an In0.53Ga0.47As-based semiconductor nanostructure. J Phys: Condens Matter 18:7961-7974, 2006.
82. Kiang JG, Tsen KT. Biology of hypoxia. Chin J Physiol 49:223-233, 2006.
83. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Observation of the low frequency vibrational modes of bacteriophage M13 in water by Raman spectroscopy. Virology J 3:79 (11 pages), 2006.
84. Tsen KT, Dykeman E, Sankey OF, Lin N-T, Tsen S-WD, Kiang JG. Raman scattering studies of the low frequency vibrational modes of bacteriophage M13 in water. Nanotecnology 17:5474-5479, 2006.
85. Tsen KT, Kiang JG, Ferry DK, and Morkoc H. Subpicosecond time-resolved Raman studies of field-induced transient transport in an -based p-i-n semiconductor nanostructure. App Physics Lett, 89: 262101 (3 pages), 2006.
86. Tsen KT, Kiang JG, and Ferry DK. Subpicosecond transient Raman scattering studies of field-induced electron transport in an -based p-i-n nanostructure: Direct observation of the effects of electron momentum randomization. J Phys: Condens Matter 18:L585-L592, 2006.
87. Kiang JG, Peckham RM, Duke LE, Chaudry IH, Tsokos GC. Androstenediol inhibits trauma-hemorrhage-induced increase in caspase-3 by downregulating inducible nitric oxide synthase pathway. J App Physiol 102: 933-941, 2007.
88. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Probing the low frequency vibrational modes of viruses with Raman scattering -- bacteriophage M13 in water. J Biomed Optics. 12: 024009 (6 pages), 2007.
89. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN. Proc of SPIE 6473: 64730Q-1 – 64730Q-12, 2007.
90. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Studies of longitudinal optical phonons in GaN by sybpicosecond time-resolved Raman Spectroscopy. Proc of SPIE 6471: 64710X-1 – 64710X-10, 2007.
91. Kiang JG, Bowman DP, Lu X, Li Y, Wu BW, Loh HH, Tsen KT, Tsokos GC. Geldanmaycin treatment inhibits hemorrhage-induced increases in caspase-3 activity: Role of inducible nitric oxide synthase. J App Physiol 103: 1045-1055, 2007.
92. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Direct measurements of the lifetimes of longitudinal optical phonon modes and their dynamics in InN. App Physics Lett 90: 152107 (3 pages), 2007.
93. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Subpicosecond time-resolved Raman studies of electron-longitudinal optical phonon interactions in InN. App Physics Lett 90: 172108 (3 pages), 2007.
94. Tsen KT, Kiang JG, Ferry DK, Lu H, Schaff WJ, Lin HW, Gwo S. Electron-density dependence of longitudinal-optical phonon lifetime in InN studied by subpicosecond time-resolved Raman spectroscopy. J Phy Condens Matter 19: 236219 (8 pages), 2007.
95. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by coherent excitations with low power visible femtosecond laser. Virology J 4:50 (6 pages), 2007.
96. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses with a very low power visible femtosecond laser. J Physics: Condens Matter 19:322102 (9 pages), 2007.
97. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by laser-driven coherent excitations via impulsive stimulated Raman scattering process. J Biomed Optics 12:064030 (6 pages), 2007.
98. Tsen KT, TsenS-W D, Sankey OF, Kiang JG. Selective inactivation of microorganisms by near-IR femosecond laser pulses. J Phy Condens Matter 19: 472201 (7 pages), 2007.
99. Kiang JG, Krishnan S, Lu X, Li Y. Inhibition of inducible nitric oxide synthase protects human T cells from hypoxia-induced injury. Mol Pharmacol 73:738-747, 2008.
100. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kiang JG. Selective inactivation of human immunodeficiency virus with subpicosecond near-infrared laser pulses. J Phys Condens matter 20:25220 (4 pages), 2008.
101. Atkins JL, Hammamiech R, Jett M, Gorbounov NV, Asher LV, Kiang JG. α-Defensin-4 and asymmetric dimethyl arginine (ADMA) increase in mesenteric lymph after hemorrhage in anesthetized rats. Shock 30: 411-146, 2008.
102. Tsen KT, Tsen S-W D, Chang C-L, Hung C-F, Wu T-C, Ramakrishna K, Mossman K, Kiang JG. Inactivation of viruses with a femtosecond laser via impulsive stimulated Raman scattering. In: Optical Interactions with Tissue and Cells XIX (edited by Steven L. Jacques, William P. Roach, Robert J. Thomas), Proc. of SPIE 6854: 68540N1-6854N10, 2008.
103. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Dynamics of LO phonons in InN studied by subpicosecond time-resolved Raman spectroscopy. In: Ultrafast Phenomena in Semiconductors and Nanostructure Materials XII (edited by J.J. Song, K.T. Tsen, M. Betz and A. Elezzabi), Proc. of SPIE Vol. 6892: 689206 (12 pages), 2008.
104. Kiang JG, Kiang SC, Bowman PD. 17-DMAG inhibits hemorrhage-induced injury in small intestine and lung by inactivating caspase-3. International Proceedings of International Shock Congress K628C0171:23-27, 2008.
105. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kibler K, Jacob B, Kiang JG. Selective inactivation of human immunodeficiency virus with an ultrashort pulsed laser. Proc. of SPIE 7175: 717510-1 – 717510-8, 2009.
106. Kiang JG, Smith JA, and Agravante NG. Geldanamycin analog 17-DMAG inhibits iNOS and caspases in gamma irradiated human T cells. Radiat Res 172: 321-330, 2009.
107. Gorbunov NV, Kiang JG. Up-regulation of Autophagy in the Small Intestine Paneth Cell in Response to Total-Body γ-Irradiation. J Pathol 219: 242-252, 2009.
108. Jiao W, Kiang JG, Cary L, Elliott TB, Pellmar TC, Ledney GD. COX-2 inhibitors are contraindicated for therapy of combined injury. Radiat Res 172: 686-697, 2009.
109. Tsen KT, Tsen S-WD, Fu Q, Lindsay SM, Kibler K, Jacobs B, Wu TC, Karanam B, Jagu S, Roden RBS, Hung C-F, Sankey OF, Ramakrishna B, Kiang JG. Photonic approach to the selective inactivation of viruses with a near-infrared subpicosecond fiber laser. J Biomed Opt 14: 064042 (10 pages), 2009.
110. Kiang JG, Jiao W, Cary L, Mog SR, Elliott TB, Pellmar TC, Ledney GD. Wound trauma increases radiation-induced mortality by increasing iNOS, cytokine concentrations, and bacterial infections. Radiate Res 173: 319-332, 2010.
111. Kiang JG, Garrison BR, Gorbunov NV. Radiation combined injury: DNA damage, apoptosis, and autophagy. Adapt Med 2: 1-10, 2010. doi: 10.4247/AM.2010.ABA004.
112. Daly MJ, Gaidamakova EK, Matrosova VY, Kiang JG, Fukumoto R, Wehr NB, Viteri G, Berlett BS, Levine RL. Small molecule proteome-shield in Deinococcus radiodurans. PLoS One 5(9): e12570 (15 pages), 2010.
113. Gorbunov NV and Kiang JG. Activation of IL-1β pathway and augmentation of Paneth cell α-defensin-4 in small intestine following total-body γ-irradiation. Intl J Immunopathol Pharmacol 23: 1111-1123, 2010.
114. Kiang JG, Smith JA, Agravante NG, Gorbunov NV. Geldanamycin analog 17-DMAG has radioprotective activity in mice. Radiat Res, in review.
115. Fukumoto R, Kiang JG. Geldanamycin analog 17-DMAG limits apoptosis in human peripheral blood cells by inhibition of p53 activation and its interaction with heat shock protein 90 kDa after ionizing radiation. Radiat Res 176: 333-345, 2011.
116. Kiang JG, Agravante NG, Smith JT, Bowman PD. 17-DMAG increases Bcl-2 and inhibits hemorrhage-induced increases in iNOS activation, caspase-3 activity and TNF-a. Cell & Bioscience 1: 21 (10 pages), 2011.
117. Tsen KT, Tsen SWD, Fu Q, Lindsay SM, Li Z, Yan H, Cope S, Vaiana S, Kiang JG. Studies of inactivation of encephalomyocaditis virus, M13 bacteriophage and Salmomella typhimurium by using a visible femtosecond laser irradiation: insight into the possible inactivation mechanisms. J Biomed Optics 16: 078003 (11 pages), 2011.
118. Whitnall MH, Cary LH, Moroni M, Ngudiankama BF, Landauer MR, Singh VK, Ghosh SP, Kulkarni S, Miller AC, Kiang JG, Srinivasan V, Xiao M. United States Armed Forces Radiobiology Research Institute countermeasures program and related policy questions. Proceedings,Hiroshima University, 2012.
119. Kiang JG, Garrison BR, Burns TM, Zhai M, Dews IC, Ney PH, Fukumoto R, Cary LH, Elliott TB, Ledney GD. Wound trauma alters ionizing radiation dose assessment. Cell Bioscience 2: 20 (12 pages), 2012.
120. Tsen S-W D, Wu TC, Kiang JG, Tsen KT. Prospects for a novel ultrashort pulsed laser technology for pathogen inactivation. J Biomed Sci 19: 62 (11 pages), 2012.
121. Kiang JG. Overview of biological effects of irradiation combined injury. NATO-HFM-223-P5:1-18, 2012.
122. Fukumoto R, Cary LH, Gorbunov NV, Elliott TB, Kiang JG. Ciprofloxacin modulates cytokine profiles, accelerates bone marrow recovery and mitigates ileum injury after radiation combined with wound trauma. PLoS One 8: e58389 (11 pages), 2013. doi: 10.1371/journal.pone.0058389. PMID: 23520506
123. Gorbunov NV, Garrison BR, McDaniel DP, Zhai M, Liao1 P-J, Nurmemet N, Kiang JG. Adaptive redox response of mesenchymal stromal cells to stimulation with lipopolysaccharide inflammagen: mechanisms of remodeling of tissue barriers in sepsis. Oxid Med Cell Longev 2013: 186795 (16 pages), 2013. doi: 10.1155/2013/186795. PMID: 23710283
124. Lu X, Nurmemet D, Bolduc DL, Elliott TB, Kiang JG. Radioprotective effects of oral 17-DMAG in mice: Bone marrow and small intestine. Cell Bioscience 3: 36 (16 pages), 2013. doi: 10.1186/2045-3701-3-36. PMID: 24499553
125. Kiang JG, Ledney GD. Skin injuries reduce survival and modulate corticosterone, C-reactive protein, complement component 3, IgM, and prostaglandin E2 after whole-body reactor-produced mixed field (n + γ-photons) irradiation. Oxid Med Cell Longev, 2013: 821541 (10 pages), 2013. doi: 10.1155/2013/821541. PMID: 24175013
126. Kiang JG, Garrison BR, Smith JT, Fukumoto R. Ciprofloxacin as a potential radio-sensitizer to tumor cells and a radioprotectant for normal cells: Differential effects on -H2AX formation, p53 phosphorylation, Bcl-2 production, and cell death. Cell Mol Biochem 393: 133-143, 2014. doi: 10.1007/s11010-014-2053-z. PMID: 24802382
127. Kiang JG, Fukumoto R. Ciprofloxacin increases survival after ionizing irradiation combined injury: gamma-H2AX formation, cytokine/chemokine, and red blood cells. Health Physics 106: 720-726, 2014. doi: 10.1097/HP.0000000000000108. PMID: 24776905
128. Fukumoto R, Burns TM, Kiang JG. Ciprofloxacin Enhances Stress Erythropoiesis in Spleen and Increases Survival after Whole-Body Irradiation Combined with Skin-Wound Trauma, PLoS One 9(2): e90448, 2014. doi: 10.1371/journal.pone.0090448. PMID: 24587369
129. Kiang JG, Zhai M, Liao P-J, Bolduc DL, Elliott TB, Gorbunov NV. Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn. Oxid Med Cell Longev 2014: 481392 (10 pages), 2014. doi: 10.1155/2014/481392. PMID: 24738019
130. Kiang JG, Zhai M, Liao P-J, Elliott TB, Gorbunov NV. Ghrelin therapy improves survival after whole-body ionizing irradiation combined with wound or burn: Amelioration of leukocytopenia, thrombopenia, splenomegaly, and bone marrow injury. Oxid Med Cell Longev 2014: 215858, 2014. doi: 10.1155/2014/215858. PMID: 25374650
131. Gorbunov NV, Elliott TB, McDaniel DP, Zhai M, Liao P-J, Kiang JG. Mitophagy and mitochondrial remodeling in mouse mesenchymal stromal cells following a challenge with Staphylococcus epidermidis. J Cell Mol Med 19:1133-1150, 2015. doi: 10.1111/jcmm.12518. PMID: 25721260
132. Kiang JG, Gorbunov NV. Bone marrow mesenchymal stem cells increases survival after ionizing irradiation combined with wound trauma: Characterization and therapy. J Cell Sci Ther 5:190 (8 pages), 2014. doi: 10.4172/2157-7013.1000190
133. Elliott TB, Bolduc DL, Ledney GD, Kiang JG, Fatanmi OO, Wise S, Romaine PLP, Newman VL, Singh VK. Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in mice exposed to radiation and combined injury. Int J Radiat Biol 91(9):690-702, 2015. doi: 10.3109/09553002.2015.1054526. PMID: 25994812
134. Swift JM, Smith JT, Kiang JG. Ciprofloxacin therapy mitigates ATP loss after irradiation combined with wound trauma: Preservation of pyruvate dehydrogenase and inhibition of pyruvate dehydrogenase kinase 1. Radiat Res 183: 684-692, 2015. PMID: 26010714
135. Swift JM, Smith JT, Kiang JG. Hemorrhage Trauma Increases Radiation-Induced Trabecular
Bone Loss and Marrow Cell Depletion in Mice. Radiat Res 183: 578-583, 2015. doi: 10.1667/RR13960.1 PMID: 25897554
136. Swift JM, Swift SN, Smith JT, Kiang JG, Allen MR. Skin wound trauma, following high-dose radiation exposure, amplifies and prolongs skeletal tissue loss. Bone 81: 487-494, 2015. doi: 10.1016/j.bone.2015.08.022 PMID: 26335157
137. Islam A, Bolduc DL, Zhai M, Kiang JG, Swift JM. Daily Captopril Dosing Increases Survival after Whole-Body Ionizing Irradiation but Decreases Survival after in combination with Combined Burn Trauma in Mice. Radiat Res 184:273-279, 2015. doi: 10.1667/RR14113.1. PMID: 26305295
138. Kiang JG, Smith JT, Anderson MN, Swift JM, Gupta P, Balakathiresan N, Maheshwari RK. Hemorrhage exacerbates radiation effects on survival, leukocytopenia, thrombopenia, erythropenia, bone marrow cell depletion and hematopoiesis, and inflammation-associated microRNAs expression in kidney. PLoS ONE 10:e0139271, 2015. doi: 10.1371/journal.pone.0139271. PMID: 26422254
139. Klionsky DJ…Kiang JG…Zughaler SM. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12: 1-222, 2016. PMID: 26799652
140. Kiang JG. Adult mesenchymal stem cells and radiation injury. Health Phys 111:198-203, 2016. doi: 10.1097/HP.0000000000000459. PMID: 27356065
141. Gupta P, Gayen M, Smith JT, Matrosova VY, Gaidamakova EK, Daly MJ, Kiang JG, Maheshwari RK. MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation. PLoS One 11: e0160575, 2016. doi: 10.1371/journal.pone.0160575. PMID: 27500529
142. Kiang JG. Exacerbation of mild hypoxia on acute radiation syndrome and subsequent mortality. Adaptive Med 9(1): 28-33, 2017. doi: 10.4247/AM.2017.ABG170
143. Kiang JG, Zhai M, Liao P.-J., Ho C, Gorbunov NV, Elliott TB. Thrombopoietin receptor agonist mitigate hematopoietic acute radiation syndrome and improves survival after whole-body ionizing irradiation followed by wound trauma. Mediators of Inflammation 2017:7582079, 2017. doi: 10.1155/2017/7582079 PMID: 28408792
144. Kiang JG, Zhai M, Bolduc DL, Smith JT, Anderson MN, Ho C, Lin B, Jiang S. Combined therapy of pegylated-G-CSF and Alx4100TPO improves survival and mitigate acute radiation syndrome after whole-body ionizing irradiation alone and followed by wound trauma. Radiat Res 188:476-490, 2017. doi: 10.1667/RR14647.1 PMID: 28850300
145. Kiang JG, Smith JT, Anderson MN, Elliott TB, Gupta P, Balakathiresan N, Maheshwari RK, Knollmann-Ritschel B. Hemorrhage enhances cytokine, complement component 3, and caspase-3, and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury. PLoS ONE 12(9):e0184393, 2017. doi: 10.1371/journal.pone.0184393.PMID: 28934227
146. Gorbunov NV, Kiang JG. Ghrelin therapy decreases incidents of intracranial hemorrhage in mice after whole-body ionizing irradiation combined with burn trauma. Int J Mol Sci 18(8). pii: E1693, 2017. doi: 10.3390/ijms18081693. PMID: 28771181
147. Kiang JG, Smith JT, Hegge SR, Ossetrova N. Circulating cytokine/chemokine concentrations respond to ionizing radiation doses but not radiation dose rates: granulocyte-colony stimulating factor and interleukin-18. Radiat Res, in press, 2018.
148. Kiang JG, Anderson MN, Smith JT. Ghrelin therapy sustains granulocyte colony-stimulating factor and keratinocyte factor to mitigate hematopoietic syndrome and spleen after whole-body ionizing irradiation combined with wound. Cell Biosci 8:27, 2018. doi: 10.1186/s13578-018-0225-3.
149. Li X, Cui W, Hull L, Smith JT, Kiang JG, Xiao M. Effects of low-moderate doses of γ-radiation on mouse hematopoietic and immune system. Radiat Res, in review, 2018.
E-Book (1)
1. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. Cell Biology Research Progress, Nova Science Publishers, INC. Hauppauge, NY. ISBN: 978-1-62417-374-5 http://www.novapublishers.com, 2012.
Book chapters (10)
1. Yan X, Lu PY, and Kiang JG. Qigong: basic science studies in Biology. In: Healing, Intention, and Energy medicine Science, Research Methods and Clinical Implications. (Eds. WB Jonas and C Crawford) Churchill Livingstone, London, UK pp. 103-119, 2003.
2. Kiang JG and McClain DE. Heat stress. In: Combat Medicine Basic and Clinical Research in Military, Trauma, and Emergency Medicine (Eds. GC Tsokos and JL Atkins), Humana Press, New Jersey, pp. 83-101, 2003.
3. Kiang JG. Human bioenergy effects at the cellular and molecular level. In: Life and Mind In Search of Physical Basis (ed. S. Savva), Trafford Publishing, Victoria BC, Canada, pp. 117-137, 2007.
4. Tsen KT, Tsen SWD, Dykeman EC, Sankey OF, Kiang JG. Inactivation of viruses with femtosecond laser pulses. In: Contemporary Trends in Bacteriophage research (Ed: Horace T. Adams), Nova Science Publishers, NY, ISBN: 978-1-60692-181-4, pp. 151-177, 2009.
5. Kumar KS, Kiang JG, Whitnall MH, Hauer-Jensen M. Perspectives in radiological and nuclear countermeasures. In: Textbook of Military Medicine, pages 239-266, 2012.
6. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. In: Autophagy: Principles, Regulation and Roles in Disease (ed: Gorbunov NV), Nova Science Pulbishers, INC. Hauppauge, NY. 2012.
7. Gorbunov NV, Garrison BR, Zhai M, McDaniel DP, Ledney GD, Elliott TB, Kiang JG. Autophagy-mediated defense response of mouse mesenchymal stromal cells (MSCs) to challenge with Escherichia coli. In: Protein Interaction / Book 1; ISBN 979-953-307-577-7. Eds.: Cai J and Wang H. InTech Open Access Publisher; www.intechweb.org. pp. 23-44, 2012.
8. Kiang JG, Fukumoto R, Gorbunov NV. Lipid peroxidation after ionizing irradiation leads to apoptosis and autophagy. In: Lipid Peroxidation; ISBN 980-953-307-143-0. Eds.: Angel Catala, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp.261-278, 2012.
9. Gorbunov NV, Elliott TB, McDaniel DP, Lund K, Liao PJ, Zhai M, Kiang JG. Up-regulation of autophagy defense mechanisms in mouse mesenchymal stromal cells in response to ionizing irradiation followed by bacterial challenge. In: Autophagy, ISBN 980-953-307-971-9. Ed: Yannick Bailly, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp. 331-350, 2013.
10. Kiang JG. Characterization and therapeutic uses of adult mesenchymal stem cells. In: Stem Cell Toxicity and Medicine (ed. S.C. Sahu). Wiley & Sons, West Sussex, pp. 288-301, 2016.
Dr. Kiang serves in editorial boards of several scientific journals, NIH and VA study sections, and USU committees. She worked in Water Reed Army Institute of Research from 1989 to 2006 before joining AFRRI.
Dr. Kiang is involved in studies showing corticotrophin-releasing factor and heat shock proteins are capable of protecting against edema/inflammation and hypoxia injury, respectively. She demonstrates that overexpression of inducible form of heat shock protein 70 kDa induced by sublethal heat stress, chemical stimulation, or the gene transfer produces thermotolerance and cross-tolerance that may be related to an inhibition of changes in intracellular calcium concentrations and expression of stress-related genes and proteins such as inducible nitric oxide synthase and p38-MAPK. She has found 17-DMAG, mesenchymal stem cells, G-CSF, ghrelin, or ciprofloxacin that can make cells endure much better under circumstances of low oxygen, a way to treat heat stroke, ischemia, hemorrhage, cancer, heart attack, stroke, or ionizing radiation injury.
Dr. Kiang had made four major contributions in her research career (journal references to work are noted).
Dr. Kiang is the first to demonstrate that treatment with corticotrophin-releasing factor (CRF) inhibits neurogenic and thermally-induced protein extravasation in rats (9-14). She also found that urotensin I and sauvagine (members of the CRF superfamily) possess the same properties as CRF but with greater potency (15). She holds a patent resulting from this work. She has provided evidence that CRF and its analogs increase intracellular Ca2+ concentrations in vitro (33, 36, 50), which are correlated with capacity of these neuropeptides to inhibit thermally-induced edema (50). CRF exerts its action on CRF type 2 receptors to activate enzymes such as tyrosine kinases, phospholipase 1 and 2 to lead to a result of increases in intracellular Ca2+ concentrations (56). A patent is resulted.
Dr. Kiang’s second major contribution is that she performed extensive research to establish the effect of heat shock on components of signal transduction pathways, such as H+, Ca2+, Na+, cAMP, inositol 1,4,5-trisphosphate, and heat shock proteins in cultured cells. Her findings in this area are wide-ranging and have extended knowledge in the heat shock field (18, 19, 22, 25, 29, 40-42, 44, 46-48, 51-55, 57, 58, 60-62). Her findings provide insight to unfold the mechanisms of tolerance and cross-tolerance (64, 67). Heat shock protein 70 kDa plays a very important role in cell survival – a fine-line before occurrence of apoptosis.
Dr. Kiang’s third major contribution is that she has shown heat shock protein 70 kDa (HSP-70i) can protect the rat ileum from the ischemia/reperfusion injury (37, 66), ricin injury (47), during ileitis (57), and the mouse jejunum, lung, heart, and kidney from the hemorrhagic shock (70). She has also shown that down-regulation of inducible nitric oxide synthase inhibits the activity of caspase-3, an apoptotic protease, and overexpression of HSP-70i prevents ATP loss resulted from hemorrhage (78, 87, 91, 99, 104) or radiation-injury (106-108, 110-114). The work has resulted in a provisional patent.
Dr. Kiang’s fourth major contribution is that she has characterized radiation combined injury (110, 111, 115, 120) shown that ciprofloxacin (122, 126-128, 134), ghrelin (130, 146), and bone marrow mesenchymal stem cells (132, 140) can combat radiation injury combined with skin-wound injury. The research work is ongoing. Meanwhile, she established a new combined injury model of radiation with hemorrhage (135, 138, 142, 145) that brought her the 2016 AFRRI Research Award.
Bubliography
Peer-reviewed publications (149)
1. Kiang JG, Dewey WL, and Wei ET. Tolerance to morphine bradycardia in the rat. J. Pharmacol Exp. Ther. 226:187 192, 1983.
2. Kiang JG and Wei ET. Inhibition of an opiate-induced vagal reflex in rats by naloxone, SMS 201 995 and ICI 154, 129. Regulatory Peptides 6:255 262, 1983.
3. Dashwood MR, Kiang JG, and Wei ET. An etorphine-evoked reflex in rats is inhibited by naloxone, N-methylnaloxone, and SMS 201 995. Arch. Int. Pharmacodyn. Ther. 266:77 82, 1983.
4. Kiang JG and Wei ET. Sensitivity to morphine-evoked bradycardia in rats is modified by dynorphin (1 13), (Leu)enkephalin and (Met)enkephalin. J. Pharmacol. Exp. Ther. 229:469 473, 1984.
5. Kiang JG and Wei ET. Peripheral opioid receptors influencing heart rate in rats: evidence for endogenous tolerance. Regulatory Peptides 8:297 303, 1984.
6. Tang J, Webber RJ, Chang D, Chang JK, Kiang JG, and Wei ET. Depressor and natriuretic activities of several atrial peptides. Regulatory Peptides 9:543 549, 1984.
7. Wei ET and Kiang JG. Peripheral opioid receptors influencing heart rate in rats. In: Opioid Peptides in the Periphery. (Eds, F. Fraioli, A. Isidori and M. Mazzetti) Developments in Neuroscience 18:95 101, 1984, Amsterdam, Elsevier.
8. Kiang JG and Wei ET. CRF-evoked bradycardia in urethane-anesthetized rats is blocked by naloxone. Peptides 6:409 413, 1985.
9. Kiang JG and Wei ET. CRF: an inhibitor of neurogenic plasma extravasation produced by saphenous nerve stimulation. Eur. J. Pharmacol. 114:111 112, 1985.
10. Wei ET, Kiang JG, Buchan P, and Smith T. Corticotropin-releasing factor (CRF) inhibits neurogenic plasma extravasation in the rat paw. J. Pharmacol. Exp. Ther. 238:783 787, 1986.
11. Kiang JG and Wei ET. Corticotropin-releasing factor (CRF) inhibits thermal injury. J. Pharmacol. Exp. Ther. 243:517- 520, 1987.
12. Wei ET and Kiang JG. Inhibition of protein exudation from the trachea by corticotropin-releasing factor. Eur. J. Pharmacol. 140:63-67, 1987.
13. Wei ET, Kiang JG, and Tien JQ. Anti-inflammatory activity of corticotropin-releasing factor: I. Efficacy studies. Proc. West. Pharmacol. Soc. 30:59 62, 1987.
14. Kiang JG, Poree L, and Wei ET. Anti-inflammatory activity of corticotropin-releasing factor: II. Mechanisms of action. Proc. West. Pharmacol. Soc. 30:63 65, 1987.
15. Wei ET and Kiang JG. Peptides of the corticoliberin superfamily attenuate thermal and neurogenic inflammation in rat paw skin. Eur. J. Pharmacol. 168:81 86, 1989.
16. Kiang JG and Colden-Stanfield M. Morphine induces an intracellular alkalinization in bovine aortic endothelial cells (BAECs), In: International Narcotic Research Conference (INRC) '89. (Eds. R. Quirion, K. Jhamandas and C. Gianoulakis) Alan Liss Press, N.Y., Prog. Clin. Biol. Res. 328:137 140, 1989.
17. Wei ET, Wong JC, and Kiang JG. Decreased inflammatory responsiveness of hypophysectomized rats to heat is reversed by a CRF antagonist. Regulatory Peptides 27:317 323, 1990.
18. Kiang JG, McKinney LC, and Gallin EK. Heat induces an intracellular acidification in human A 431 cells: role of Na+/H+ exchanger and metabolism. Am. J. Physiol., 259(Cell Physiol. 28):C727-C737, 1990.
19. Kiang JG, Wu YY, and Lin M. Hyperthermia elevates cAMP levels in human epidermoid A 431 cells. Biochem. J. 276:683 689, 1991.
20. Kiang JG. Effect of intracellular pH on cytosolic free [Ca2+]i in A-431 cells. Eur. J. Pharmacol. 207(Molecular Pharmacol. Section):287-296, 1991.
21. Lin W-W, Kiang JG, and Chuang D-M. Pharmacological characterization of endothelin-stimulated phosphoinositides breakdown and cytosolic Ca2+ rise in C6 rat glioma cells. J. Neurosci., 12:1077 1085, 1992.
22. Kiang JG, Koenig ML, and Smallridge RC. Heat shock increases cytosolic free Ca2+ concentration via the Na+/Ca2+ exchange in human epidermoid A 431 cells. Am. J. Physiol. 263(Cell Physiol. 32):C30-38, 1992.
23. Smallridge RC, Gist ID, and Kiang JG. Na+-H+ antiport and monensin effects on cytosolic pH and iodide transport in FRTL 5 rat thyroid cells. Am. J. Physiol. 262(Endocrinol. Metab.) 25:E834-E839, 1992.
24. Smallridge RC, Kiang JG, Gist ID, Fein HG, and Galloway R. U 72133 inhibits TRH-induced activities in GH3 cells. Endocrinol. 131:1883 1888, 1992.
25. Kiang JG and McClain DE. Effect of heat shock, Ca2+, and cAMP on inositol 1,4,5-trisphosphate in human epidermoid A 431 cells. Am. J. Physiol. 264 (Cell Physiol. 33):C1561-C1569, 1993.
26. Aloj SM, Liguoro D, Kiang JG, and Smallridge RC. Purinergic (P2) receptor -operated calcium entry into rat thyroid cells. Biophy. Biochim. Res. Comm. 195:1-7, 1993.
27. Kiang JG. Corticotropin-releasing factor increases cytosolic free calcium via receptor-mediated Ca2+ channels. Eur. J. Pharmacol. (Molecular Pharmacol. Section) 267:135-142, 1994.
28. Kiang JG and Smallridge RC. Sodium cyanide increases cytosolic free calcium: Evidence of activation of the reversed mode of Na+/Ca2+ exchanger and Ca2+ mobilization from inositol trisphosphate-insensitive pools. Toxicol. Appl. Pharmacol., 127:173-181, 1994.
29. Kiang JG, Carr FE, Burns MR, and McClain DE. HSP-72 synthesis is promoted by increase in [Ca2+]i or activation of G proteins but not pHi or cAMP. Am. J. Physiol. 267 (Cell Physiol. 36):C104-C114, 1994.
30. Tang T, Kiang JG, and Cox BM. Opioids acting through delta-receptors increase the intracellular free calcium concentration in the dorsal root ganglion neuroblastoma hybrid ND8-47 cells. J. Pharmacol. Exptl. Ther., 270:40-46, 1994.
31. Wang X, Kiang JG, and Smallridge RC. U-73122 inhibits increases in inositol trisphosphates and cytosolic free [Ca2+] induced by TSH in FRTL-5 cells. Bioph. Biochim. Acta, 1223:101-106, 1994.
32. Poola I and Kiang JG. The estrogen inducible transferrin receptor-like membrane glycoprotein is related to stress regulated proteins. J. Biol. Chem. 269:1-8, 1994.
33. Kiang JG, Wang XD, and McClain DE. Corticotropin-releasing factor increases protein kinase C activity by elevating isoforms and at the membrane. Chin J. Physiol. 37:105-110, 1994.
34. Wang XD, Kiang JG, and Smallridge RC. Identification of protein kinase C and its multiple isoforms in Frtl-5 thyroid cells. Thyroid 5:137-140, 1995.
35. Tang T, Kiang JG, Cote T, and Cox BM. Opioid-induced increase [Ca2+]i in ND8-47 neuroblastoma X DRG hybrid cells is mediated through G protein-coupled delta opioid receptors and desensitized by chronic exposure to opioid. J. Neurochem. 65:1612-1621, 1995.
36. Kiang JG. Mystixin-7 and Mystixin-11 increase [Ca2+]i and inositol trisphosphates in human A-431 cells. Eur. J. Pharmacol. (Mol. Pharmacol. Section) 291:107-113, 1995.
37. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Heat shock protein 72 kD induction protects rat intestinal mucosa from ischemia/reperfusion injury. Gastroenterol. 109:505-515, 1995.
38. Tang T, Kiang JG, Cote T, and Cox BM. Antisense oligodeoxynucleotide to Gái2 protein á-subunit sequence inhibits an opioid-induced increase in intracellular free calcium in ND8-47 neuroblastoma x DRG hybrid cells. Mol. Pharmacol. 48:189-193, 1995.
39. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Rapid assay of HSF1 and HSF2 gene expression by reverse transcriptase PCR. Mol. Cell Biochem. 158: 48-51, 1996.
40. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Increases in HSF1 translocation and synthesis in human epidermoid A-431 cells: role of protein kinase C and [Ca2+]i. J. Investig. Med. 44:144-153, 1996.
41. Kiang JG, Ding XZ, and McClain DE. Thermotolerance attenuates heat-induced increases in [Ca2+]i and HSP-72 synthesis but not heat-induced intracellular acidification in human A-431 cells. J. Investig. Med. 44:189-192, 1996.
42. Kiang JG, Wang XD, Ding XZ, Gist I, and Smallridge RC. Heat shock inhibits the hypoxia-induced effects on iodide uptake and signal transduction and enhances cell survival in rat thyroid FRTL-5 cells. Thyroid, 6:475-483, 1996.
43. Wang XD, Kiang JG, Atwa MA, and Smallridge RC. Evidence for the involvement of protein kinase C isoforms in á-1 adrenergic activation of phospholipase A2 in Frtl-5 thyroid cells, J. Investig. Med. 44:566-574, 1996.
44. Kiang JG and Koenig ML. Characterization of intracellular calcium pools in thermotolerant and their desensitization in thermotolerant cells. J. Investig. Med. 44:352-361, 1996.
45. Kiang JG and Tsokos GC. Signal transduction and heat shock protein expression. J. Biomed. Sci. 3:379-388, 1996.
46. Ding XZ, Tsokos GC, Smallridge RC, and Kiang JG. Heat shock gene expression in HSP-70 and HSF1 gene-transfected human epidermoid A-431 cells. Mol. Cell. Biochem. 167:145-152, 1997.
47. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Induction of the heat shock response limits tissue injury during acute inflammation of the rat ileum. Critical Care Medicine 25:309-317, 1997.
48. Ding XZ, Tsokos GC, and Kiang JG. Heat shock factor 1 protein in heat shock factor 1 gene-transfected human epidermoid A-431 cells requires phosphorylation prior to inducing heat shock protein-70 production. J. Clin. Investig. 99:136-143, 1997.
49. Liossis S-N, Ding XZ, Kiang JG, and Tsokos GC. Overexpression of HSP70 offers thermoprotection but enhances the TCR/CD3- and Fas-induced apoptotic death in Jurkat T-cells. J. Immunol. 158:5668-5675, 1997.
50. Kiang JG. Corticotropin-releasing factor-like peptides increase cytosolic free calcium in human epidermoid A-431 cells. Eur. J. Pharmacol. (Molecular Pharmacology Section), 329:237-244, 1997.
51. Kiang JG, Gist ID, and Tsokos GC. 17-Estradiol-induced increases in glucose-regulated proteins protect human breast cancer T47-D cells from thermal injury. Chin. J. Physiol. 40:213-219, 1997.
52. Kiang JG, Ding XZ, and McClain DE. Overexpression of HSP-70 attenuates increases in [Ca2+]i and protects human epidermoid A-431 cells after chemical hypoxia. Toxicol. Appl. Pharmacol. 149:185-194, 1998.
53. Ding XZ, Tsokos GC, and Kiang JG. Overexpression of HSP-70 inhibits the phosphorylation of HSF1 by activating protein phosphatase and inhibiting protein kinase C activity. FASEB. J. 12:451-459, 1998.
54. Kiang JG, Gist ID, and Tsokos GC. Cytoprotection and regulation of heat shock proteins induced by heat shock in human breast cancer T47-D cells: role of [Ca2+]i and protein kinases. FASEB J. 12: 1571-1579, 1998.
55. Kiang JG and Tsokos GC. Heat shock protein 70 kD family: Molecular Biology, Biochemistry, and Physiology. Pharmacol.Ther. 80:183-201, 1998.
56. Kiang JG, Ding XZ, Gist ID, and Tsokos GC. Corticotropin-releasing factor increases phosphotyrosine of phospholipase C- at tyrosine residues via its receptor 2 in human epidermoid A-431 cells. Eur. J. Pharmacol. 363:203-210, 1998.
57. Goldhill JM, Stojadinovic A, KiangJG, Smallridge RC, and Shea-Donohue T. Hyperthermia prevents functional, histological and biochemical abnormalities induced during ileitis. Neurogastroenterol. Mot. 11:69-76, 1999.
58. Kiang JG, Gist ID, and Tsokos GC. Biochemical requirement of heat shock protein 72 kD expression in human breast cancer MCF-7 cells. Mol. Cell. Biochem.199: 179-188, 1999.
59. Wang XD, Kiang JG, Scheibel LW, and Smallridge RC. Phospholipase C activation by Na+/Ca2+ exchange is essential for monensin-induced Ca2+ influx and arachidonic release in FRTL-5 thyroid cells. J. Investig. Med., 47:388-396, 1999.
60. Kiang JG and McClain DE. N-nitro-L-arginine decreases resting cytosolic [Ca2+] and enhances heat stress-induced increase in cytosolic [Ca2+] in human colon carcinoma T84 cells. Chin. J. Physiol. 42: 153-160, 1999.
61. Smallridge RC, Gist ID, Tsokos GC, and Kiang JG. Characterization of distinct heat shock and thapsigargin-induced cytoprotective proteins in FRTL-5 cells. Thyroid, 9: 1041-1047, 1999.
62. Kiang JG, Gist ID, and Tsokos GC. Heat shock induces expression of heat shock protein 72 kD and 90 kD in human breast cancer MDA-231 cells. Mol. Cell. Biochem. 204: 169-178, 2000.
63. Kiang JC and Lu PY. Biological effects of qigong and an overview of research design and methodology. Proceedings: The Science and Spirituality of Healing, 1: 99-121, 2000.
64. Kiang JG, Kiang SC, Juang Y-T, and Tsokos GC. Nω-nitro-L-arginine inhibits the inducible heat shock protein 70 kDa via Ca2+, PKC, and PKA. Am. J. Physiol. 282:G415-G423, 2002.
65. Kiang JG, Marotta D, Wirkus M, Wirkus M, and Jonas WB. External bioenergy increases intracellular free calcium concentrations and reduces cellular response to heat stress. J. Investig. Med., 50: 38-45, 2002.
66. Fleming SD, Starnes BW, Kiang JG, Stojadinovic A, Tsokos GC, and Shea-Donohue T. Heat stress protection against mesenteric ischemia/reperfusion-induced alteration in intestinal mucosa in rats. J. Appl. Physiol. 92:2600-2607, 2002.
67. Kiang JG. Genistein inhibits herbimycin A-induced inducible heat shock protein 70 kDa. Mol Cell Biochem, 245:191-199, 2003.
68. Kiang JG, McClain DE, Warke VG, Krishnan S, and Tsokos GC. Constitutive NO synthase regulates the Na+/Ca2+ exchanger in human Jurkat T cells: role of [Ca2+]i and tyrosine phosphorylation. J. Cellular Biochem., 89:1030-1043, 2003.
69. Kiang JG, Warke VG, and Tsokos GC. NaCN-induced chemical hypoxia is associated with altered gene expression. Mol Cell Biochem 254:211-216, 2003.
70. Kiang JG, Bowman DP, Wu BW, Hampton N, Kiang AG, Zhao B, Juang Y-T, Atkins JL, and Tsokos GC. Geldanmaycin inhibits hemorrhage-induced increases in caspase-3 activity, KLF6, and iNOS expression in unresuscitated organs of mice: Role of inducible HSP-70. J Appl Phsiol 97:564-569, 2004.
71. Kiang JG, Bowman PD, Zhao B, Atkins JL, and Tsokos GC. Heat shock protein-70 inducers and iNOS inhibitors as therapeutics to ameliorate hemorrhagic shock. NATO-HFM-109-P28:1-11, 2004.
72. Fleming SD, Kiang JG, and Tsokos GC. Targeting complement in treatment of ischemia/reperfusion-induced injury. NATO-HFM-109-P24:1-13, 2004.
73. Bowman PD, Zhao B, Bynum JA, Sondeen JL, Kiang JG, Dubick MA, and Atkins JL. Application of gene expression analysis with microarrays and proteinomics to the problem of hemorrhagic shock and resuscitation. NATO-HFM-109-P29:1-15, 2004.
74. Kiang JG. Inducible heat shock protein 70 kD and inducible nitric oxide synthase in hemorrhage/resuscitation-induced injury. Cell Res 14:450-459, 2004.
75. Kiang JG, Ives JH, and Jonas WB. External bioenergy-induced increases in intracellular free calcium concentrations are mediated by the Na+/Ca2+ exchanger and L-type calcium channel. Mol Cell Biochem 271:51-59, 2005.
76. Kiang JG. Lu X, Tabaku LS, Bentley TB, Atkins JL, and Tsokos GC. Resuscitation with lactated Ringers solution limits the expression of molecular events associated with lung injury after hemorrhage. J Appl Physiol 98:550-556, 2005.
77. Krishnan S, Kiang JG, Fisher CU, Nambiar MP, Nguyen HT, Kyttaris VC, Chowdhury B, Rus V, Tsokos GC. Increased caspase-3 expression and activity contributes to reduced CD3 expression in Systemic Lupus Erythematosus T cells. J Immunol 175:3417-3423, 2005.
78. Kiang JG, Bowman DP, Lu X, Li Yansong, Ding XZ, Zhao B, Juang YT, Atkins JL, Tsokos GC. Geldanmaycin treatment prevents hemorrhage-induced ATP loss in mouse organs by overexpressing HSP-70 and activating pyruvate dehydrogenase. Am J Physiol 291:G117-G127, 2006.
79. Tsen KT, Tsen SWD, Kiang JG. Lycopene is more potent than bata carotene in the neutralization of singlet oxygen: role of energy transfer probed by ultrafast Raman spectroscopy. J Biomed Optics 11:064025 (6 pages), 2006.
80. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN: Dependence on the injected carrier density. App Physics Lett 89:11211 (3 pages), 2006.
81. Tsen KT, Kiang JG, Ferry DK, Kochelap VA, Komirenko SM, Kim KW, Morkoc H. Subpicosecond Raman studies of electric-field-induced optical phonon instability in an In0.53Ga0.47As-based semiconductor nanostructure. J Phys: Condens Matter 18:7961-7974, 2006.
82. Kiang JG, Tsen KT. Biology of hypoxia. Chin J Physiol 49:223-233, 2006.
83. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Observation of the low frequency vibrational modes of bacteriophage M13 in water by Raman spectroscopy. Virology J 3:79 (11 pages), 2006.
84. Tsen KT, Dykeman E, Sankey OF, Lin N-T, Tsen S-WD, Kiang JG. Raman scattering studies of the low frequency vibrational modes of bacteriophage M13 in water. Nanotecnology 17:5474-5479, 2006.
85. Tsen KT, Kiang JG, Ferry DK, and Morkoc H. Subpicosecond time-resolved Raman studies of field-induced transient transport in an -based p-i-n semiconductor nanostructure. App Physics Lett, 89: 262101 (3 pages), 2006.
86. Tsen KT, Kiang JG, and Ferry DK. Subpicosecond transient Raman scattering studies of field-induced electron transport in an -based p-i-n nanostructure: Direct observation of the effects of electron momentum randomization. J Phys: Condens Matter 18:L585-L592, 2006.
87. Kiang JG, Peckham RM, Duke LE, Chaudry IH, Tsokos GC. Androstenediol inhibits trauma-hemorrhage-induced increase in caspase-3 by downregulating inducible nitric oxide synthase pathway. J App Physiol 102: 933-941, 2007.
88. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Probing the low frequency vibrational modes of viruses with Raman scattering -- bacteriophage M13 in water. J Biomed Optics. 12: 024009 (6 pages), 2007.
89. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN. Proc of SPIE 6473: 64730Q-1 – 64730Q-12, 2007.
90. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Studies of longitudinal optical phonons in GaN by sybpicosecond time-resolved Raman Spectroscopy. Proc of SPIE 6471: 64710X-1 – 64710X-10, 2007.
91. Kiang JG, Bowman DP, Lu X, Li Y, Wu BW, Loh HH, Tsen KT, Tsokos GC. Geldanmaycin treatment inhibits hemorrhage-induced increases in caspase-3 activity: Role of inducible nitric oxide synthase. J App Physiol 103: 1045-1055, 2007.
92. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Direct measurements of the lifetimes of longitudinal optical phonon modes and their dynamics in InN. App Physics Lett 90: 152107 (3 pages), 2007.
93. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Subpicosecond time-resolved Raman studies of electron-longitudinal optical phonon interactions in InN. App Physics Lett 90: 172108 (3 pages), 2007.
94. Tsen KT, Kiang JG, Ferry DK, Lu H, Schaff WJ, Lin HW, Gwo S. Electron-density dependence of longitudinal-optical phonon lifetime in InN studied by subpicosecond time-resolved Raman spectroscopy. J Phy Condens Matter 19: 236219 (8 pages), 2007.
95. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by coherent excitations with low power visible femtosecond laser. Virology J 4:50 (6 pages), 2007.
96. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses with a very low power visible femtosecond laser. J Physics: Condens Matter 19:322102 (9 pages), 2007.
97. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by laser-driven coherent excitations via impulsive stimulated Raman scattering process. J Biomed Optics 12:064030 (6 pages), 2007.
98. Tsen KT, TsenS-W D, Sankey OF, Kiang JG. Selective inactivation of microorganisms by near-IR femosecond laser pulses. J Phy Condens Matter 19: 472201 (7 pages), 2007.
99. Kiang JG, Krishnan S, Lu X, Li Y. Inhibition of inducible nitric oxide synthase protects human T cells from hypoxia-induced injury. Mol Pharmacol 73:738-747, 2008.
100. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kiang JG. Selective inactivation of human immunodeficiency virus with subpicosecond near-infrared laser pulses. J Phys Condens matter 20:25220 (4 pages), 2008.
101. Atkins JL, Hammamiech R, Jett M, Gorbounov NV, Asher LV, Kiang JG. α-Defensin-4 and asymmetric dimethyl arginine (ADMA) increase in mesenteric lymph after hemorrhage in anesthetized rats. Shock 30: 411-146, 2008.
102. Tsen KT, Tsen S-W D, Chang C-L, Hung C-F, Wu T-C, Ramakrishna K, Mossman K, Kiang JG. Inactivation of viruses with a femtosecond laser via impulsive stimulated Raman scattering. In: Optical Interactions with Tissue and Cells XIX (edited by Steven L. Jacques, William P. Roach, Robert J. Thomas), Proc. of SPIE 6854: 68540N1-6854N10, 2008.
103. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Dynamics of LO phonons in InN studied by subpicosecond time-resolved Raman spectroscopy. In: Ultrafast Phenomena in Semiconductors and Nanostructure Materials XII (edited by J.J. Song, K.T. Tsen, M. Betz and A. Elezzabi), Proc. of SPIE Vol. 6892: 689206 (12 pages), 2008.
104. Kiang JG, Kiang SC, Bowman PD. 17-DMAG inhibits hemorrhage-induced injury in small intestine and lung by inactivating caspase-3. International Proceedings of International Shock Congress K628C0171:23-27, 2008.
105. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kibler K, Jacob B, Kiang JG. Selective inactivation of human immunodeficiency virus with an ultrashort pulsed laser. Proc. of SPIE 7175: 717510-1 – 717510-8, 2009.
106. Kiang JG, Smith JA, and Agravante NG. Geldanamycin analog 17-DMAG inhibits iNOS and caspases in gamma irradiated human T cells. Radiat Res 172: 321-330, 2009.
107. Gorbunov NV, Kiang JG. Up-regulation of Autophagy in the Small Intestine Paneth Cell in Response to Total-Body γ-Irradiation. J Pathol 219: 242-252, 2009.
108. Jiao W, Kiang JG, Cary L, Elliott TB, Pellmar TC, Ledney GD. COX-2 inhibitors are contraindicated for therapy of combined injury. Radiat Res 172: 686-697, 2009.
109. Tsen KT, Tsen S-WD, Fu Q, Lindsay SM, Kibler K, Jacobs B, Wu TC, Karanam B, Jagu S, Roden RBS, Hung C-F, Sankey OF, Ramakrishna B, Kiang JG. Photonic approach to the selective inactivation of viruses with a near-infrared subpicosecond fiber laser. J Biomed Opt 14: 064042 (10 pages), 2009.
110. Kiang JG, Jiao W, Cary L, Mog SR, Elliott TB, Pellmar TC, Ledney GD. Wound trauma increases radiation-induced mortality by increasing iNOS, cytokine concentrations, and bacterial infections. Radiate Res 173: 319-332, 2010.
111. Kiang JG, Garrison BR, Gorbunov NV. Radiation combined injury: DNA damage, apoptosis, and autophagy. Adapt Med 2: 1-10, 2010. doi: 10.4247/AM.2010.ABA004.
112. Daly MJ, Gaidamakova EK, Matrosova VY, Kiang JG, Fukumoto R, Wehr NB, Viteri G, Berlett BS, Levine RL. Small molecule proteome-shield in Deinococcus radiodurans. PLoS One 5(9): e12570 (15 pages), 2010.
113. Gorbunov NV and Kiang JG. Activation of IL-1β pathway and augmentation of Paneth cell α-defensin-4 in small intestine following total-body γ-irradiation. Intl J Immunopathol Pharmacol 23: 1111-1123, 2010.
114. Kiang JG, Smith JA, Agravante NG, Gorbunov NV. Geldanamycin analog 17-DMAG has radioprotective activity in mice. Radiat Res, in review.
115. Fukumoto R, Kiang JG. Geldanamycin analog 17-DMAG limits apoptosis in human peripheral blood cells by inhibition of p53 activation and its interaction with heat shock protein 90 kDa after ionizing radiation. Radiat Res 176: 333-345, 2011.
116. Kiang JG, Agravante NG, Smith JT, Bowman PD. 17-DMAG increases Bcl-2 and inhibits hemorrhage-induced increases in iNOS activation, caspase-3 activity and TNF-a. Cell & Bioscience 1: 21 (10 pages), 2011.
117. Tsen KT, Tsen SWD, Fu Q, Lindsay SM, Li Z, Yan H, Cope S, Vaiana S, Kiang JG. Studies of inactivation of encephalomyocaditis virus, M13 bacteriophage and Salmomella typhimurium by using a visible femtosecond laser irradiation: insight into the possible inactivation mechanisms. J Biomed Optics 16: 078003 (11 pages), 2011.
118. Whitnall MH, Cary LH, Moroni M, Ngudiankama BF, Landauer MR, Singh VK, Ghosh SP, Kulkarni S, Miller AC, Kiang JG, Srinivasan V, Xiao M. United States Armed Forces Radiobiology Research Institute countermeasures program and related policy questions. Proceedings,Hiroshima University, 2012.
119. Kiang JG, Garrison BR, Burns TM, Zhai M, Dews IC, Ney PH, Fukumoto R, Cary LH, Elliott TB, Ledney GD. Wound trauma alters ionizing radiation dose assessment. Cell Bioscience 2: 20 (12 pages), 2012.
120. Tsen S-W D, Wu TC, Kiang JG, Tsen KT. Prospects for a novel ultrashort pulsed laser technology for pathogen inactivation. J Biomed Sci 19: 62 (11 pages), 2012.
121. Kiang JG. Overview of biological effects of irradiation combined injury. NATO-HFM-223-P5:1-18, 2012.
122. Fukumoto R, Cary LH, Gorbunov NV, Elliott TB, Kiang JG. Ciprofloxacin modulates cytokine profiles, accelerates bone marrow recovery and mitigates ileum injury after radiation combined with wound trauma. PLoS One 8: e58389 (11 pages), 2013. doi: 10.1371/journal.pone.0058389. PMID: 23520506
123. Gorbunov NV, Garrison BR, McDaniel DP, Zhai M, Liao1 P-J, Nurmemet N, Kiang JG. Adaptive redox response of mesenchymal stromal cells to stimulation with lipopolysaccharide inflammagen: mechanisms of remodeling of tissue barriers in sepsis. Oxid Med Cell Longev 2013: 186795 (16 pages), 2013. doi: 10.1155/2013/186795. PMID: 23710283
124. Lu X, Nurmemet D, Bolduc DL, Elliott TB, Kiang JG. Radioprotective effects of oral 17-DMAG in mice: Bone marrow and small intestine. Cell Bioscience 3: 36 (16 pages), 2013. doi: 10.1186/2045-3701-3-36. PMID: 24499553
125. Kiang JG, Ledney GD. Skin injuries reduce survival and modulate corticosterone, C-reactive protein, complement component 3, IgM, and prostaglandin E2 after whole-body reactor-produced mixed field (n + γ-photons) irradiation. Oxid Med Cell Longev, 2013: 821541 (10 pages), 2013. doi: 10.1155/2013/821541. PMID: 24175013
126. Kiang JG, Garrison BR, Smith JT, Fukumoto R. Ciprofloxacin as a potential radio-sensitizer to tumor cells and a radioprotectant for normal cells: Differential effects on -H2AX formation, p53 phosphorylation, Bcl-2 production, and cell death. Cell Mol Biochem 393: 133-143, 2014. doi: 10.1007/s11010-014-2053-z. PMID: 24802382
127. Kiang JG, Fukumoto R. Ciprofloxacin increases survival after ionizing irradiation combined injury: gamma-H2AX formation, cytokine/chemokine, and red blood cells. Health Physics 106: 720-726, 2014. doi: 10.1097/HP.0000000000000108. PMID: 24776905
128. Fukumoto R, Burns TM, Kiang JG. Ciprofloxacin Enhances Stress Erythropoiesis in Spleen and Increases Survival after Whole-Body Irradiation Combined with Skin-Wound Trauma, PLoS One 9(2): e90448, 2014. doi: 10.1371/journal.pone.0090448. PMID: 24587369
129. Kiang JG, Zhai M, Liao P-J, Bolduc DL, Elliott TB, Gorbunov NV. Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn. Oxid Med Cell Longev 2014: 481392 (10 pages), 2014. doi: 10.1155/2014/481392. PMID: 24738019
130. Kiang JG, Zhai M, Liao P-J, Elliott TB, Gorbunov NV. Ghrelin therapy improves survival after whole-body ionizing irradiation combined with wound or burn: Amelioration of leukocytopenia, thrombopenia, splenomegaly, and bone marrow injury. Oxid Med Cell Longev 2014: 215858, 2014. doi: 10.1155/2014/215858. PMID: 25374650
131. Gorbunov NV, Elliott TB, McDaniel DP, Zhai M, Liao P-J, Kiang JG. Mitophagy and mitochondrial remodeling in mouse mesenchymal stromal cells following a challenge with Staphylococcus epidermidis. J Cell Mol Med 19:1133-1150, 2015. doi: 10.1111/jcmm.12518. PMID: 25721260
132. Kiang JG, Gorbunov NV. Bone marrow mesenchymal stem cells increases survival after ionizing irradiation combined with wound trauma: Characterization and therapy. J Cell Sci Ther 5:190 (8 pages), 2014. doi: 10.4172/2157-7013.1000190
133. Elliott TB, Bolduc DL, Ledney GD, Kiang JG, Fatanmi OO, Wise S, Romaine PLP, Newman VL, Singh VK. Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in mice exposed to radiation and combined injury. Int J Radiat Biol 91(9):690-702, 2015. doi: 10.3109/09553002.2015.1054526. PMID: 25994812
134. Swift JM, Smith JT, Kiang JG. Ciprofloxacin therapy mitigates ATP loss after irradiation combined with wound trauma: Preservation of pyruvate dehydrogenase and inhibition of pyruvate dehydrogenase kinase 1. Radiat Res 183: 684-692, 2015. PMID: 26010714
135. Swift JM, Smith JT, Kiang JG. Hemorrhage Trauma Increases Radiation-Induced Trabecular
Bone Loss and Marrow Cell Depletion in Mice. Radiat Res 183: 578-583, 2015. doi: 10.1667/RR13960.1 PMID: 25897554
136. Swift JM, Swift SN, Smith JT, Kiang JG, Allen MR. Skin wound trauma, following high-dose radiation exposure, amplifies and prolongs skeletal tissue loss. Bone 81: 487-494, 2015. doi: 10.1016/j.bone.2015.08.022 PMID: 26335157
137. Islam A, Bolduc DL, Zhai M, Kiang JG, Swift JM. Daily Captopril Dosing Increases Survival after Whole-Body Ionizing Irradiation but Decreases Survival after in combination with Combined Burn Trauma in Mice. Radiat Res 184:273-279, 2015. doi: 10.1667/RR14113.1. PMID: 26305295
138. Kiang JG, Smith JT, Anderson MN, Swift JM, Gupta P, Balakathiresan N, Maheshwari RK. Hemorrhage exacerbates radiation effects on survival, leukocytopenia, thrombopenia, erythropenia, bone marrow cell depletion and hematopoiesis, and inflammation-associated microRNAs expression in kidney. PLoS ONE 10:e0139271, 2015. doi: 10.1371/journal.pone.0139271. PMID: 26422254
139. Klionsky DJ…Kiang JG…Zughaler SM. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12: 1-222, 2016. PMID: 26799652
140. Kiang JG. Adult mesenchymal stem cells and radiation injury. Health Phys 111:198-203, 2016. doi: 10.1097/HP.0000000000000459. PMID: 27356065
141. Gupta P, Gayen M, Smith JT, Matrosova VY, Gaidamakova EK, Daly MJ, Kiang JG, Maheshwari RK. MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation. PLoS One 11: e0160575, 2016. doi: 10.1371/journal.pone.0160575. PMID: 27500529
142. Kiang JG. Exacerbation of mild hypoxia on acute radiation syndrome and subsequent mortality. Adaptive Med 9(1): 28-33, 2017. doi: 10.4247/AM.2017.ABG170
143. Kiang JG, Zhai M, Liao P.-J., Ho C, Gorbunov NV, Elliott TB. Thrombopoietin receptor agonist mitigate hematopoietic acute radiation syndrome and improves survival after whole-body ionizing irradiation followed by wound trauma. Mediators of Inflammation 2017:7582079, 2017. doi: 10.1155/2017/7582079 PMID: 28408792
144. Kiang JG, Zhai M, Bolduc DL, Smith JT, Anderson MN, Ho C, Lin B, Jiang S. Combined therapy of pegylated-G-CSF and Alx4100TPO improves survival and mitigate acute radiation syndrome after whole-body ionizing irradiation alone and followed by wound trauma. Radiat Res 188:476-490, 2017. doi: 10.1667/RR14647.1 PMID: 28850300
145. Kiang JG, Smith JT, Anderson MN, Elliott TB, Gupta P, Balakathiresan N, Maheshwari RK, Knollmann-Ritschel B. Hemorrhage enhances cytokine, complement component 3, and caspase-3, and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury. PLoS ONE 12(9):e0184393, 2017. doi: 10.1371/journal.pone.0184393.PMID: 28934227
146. Gorbunov NV, Kiang JG. Ghrelin therapy decreases incidents of intracranial hemorrhage in mice after whole-body ionizing irradiation combined with burn trauma. Int J Mol Sci 18(8). pii: E1693, 2017. doi: 10.3390/ijms18081693. PMID: 28771181
147. Kiang JG, Smith JT, Hegge SR, Ossetrova N. Circulating cytokine/chemokine concentrations respond to ionizing radiation doses but not radiation dose rates: granulocyte-colony stimulating factor and interleukin-18. Radiat Res, in press, 2018.
148. Kiang JG, Anderson MN, Smith JT. Ghrelin therapy sustains granulocyte colony-stimulating factor and keratinocyte factor to mitigate hematopoietic syndrome and spleen after whole-body ionizing irradiation combined with wound. Cell Biosci 8:27, 2018. doi: 10.1186/s13578-018-0225-3.
149. Li X, Cui W, Hull L, Smith JT, Kiang JG, Xiao M. Effects of low-moderate doses of γ-radiation on mouse hematopoietic and immune system. Radiat Res, in review, 2018.
E-Book (1)
1. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. Cell Biology Research Progress, Nova Science Publishers, INC. Hauppauge, NY. ISBN: 978-1-62417-374-5 http://www.novapublishers.com, 2012.
Book chapters (10)
1. Yan X, Lu PY, and Kiang JG. Qigong: basic science studies in Biology. In: Healing, Intention, and Energy medicine Science, Research Methods and Clinical Implications. (Eds. WB Jonas and C Crawford) Churchill Livingstone, London, UK pp. 103-119, 2003.
2. Kiang JG and McClain DE. Heat stress. In: Combat Medicine Basic and Clinical Research in Military, Trauma, and Emergency Medicine (Eds. GC Tsokos and JL Atkins), Humana Press, New Jersey, pp. 83-101, 2003.
3. Kiang JG. Human bioenergy effects at the cellular and molecular level. In: Life and Mind In Search of Physical Basis (ed. S. Savva), Trafford Publishing, Victoria BC, Canada, pp. 117-137, 2007.
4. Tsen KT, Tsen SWD, Dykeman EC, Sankey OF, Kiang JG. Inactivation of viruses with femtosecond laser pulses. In: Contemporary Trends in Bacteriophage research (Ed: Horace T. Adams), Nova Science Publishers, NY, ISBN: 978-1-60692-181-4, pp. 151-177, 2009.
5. Kumar KS, Kiang JG, Whitnall MH, Hauer-Jensen M. Perspectives in radiological and nuclear countermeasures. In: Textbook of Military Medicine, pages 239-266, 2012.
6. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. In: Autophagy: Principles, Regulation and Roles in Disease (ed: Gorbunov NV), Nova Science Pulbishers, INC. Hauppauge, NY. 2012.
7. Gorbunov NV, Garrison BR, Zhai M, McDaniel DP, Ledney GD, Elliott TB, Kiang JG. Autophagy-mediated defense response of mouse mesenchymal stromal cells (MSCs) to challenge with Escherichia coli. In: Protein Interaction / Book 1; ISBN 979-953-307-577-7. Eds.: Cai J and Wang H. InTech Open Access Publisher; www.intechweb.org. pp. 23-44, 2012.
8. Kiang JG, Fukumoto R, Gorbunov NV. Lipid peroxidation after ionizing irradiation leads to apoptosis and autophagy. In: Lipid Peroxidation; ISBN 980-953-307-143-0. Eds.: Angel Catala, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp.261-278, 2012.
9. Gorbunov NV, Elliott TB, McDaniel DP, Lund K, Liao PJ, Zhai M, Kiang JG. Up-regulation of autophagy defense mechanisms in mouse mesenchymal stromal cells in response to ionizing irradiation followed by bacterial challenge. In: Autophagy, ISBN 980-953-307-971-9. Ed: Yannick Bailly, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp. 331-350, 2013.
10. Kiang JG. Characterization and therapeutic uses of adult mesenchymal stem cells. In: Stem Cell Toxicity and Medicine (ed. S.C. Sahu). Wiley & Sons, West Sussex, pp. 288-301, 2016.
Representative publications, projects, and/or deployments
- Patent 1. Method of Inhibiting Inflammatory Response, Wei ET, and Kiang JG, U.S. Patent 4,801,612 (January 31, 1989)
- Patent 2. System and method for diminishing the function of microorganisms with a visible femtosecond laser, Tsen KT, Tsen SWD, and Kiang JG, U.S. Patent 60,932,668 (June 1, 2007); South Africa Patent 2010/00380 (Sep 29. 2010); China Patent CN101971008B (May 15, 2012)
- Patent 3. 17-DMAG as a radioprotectant, Kiang JG, U.S. Provisional Patent 61,122,041 (Dec 11, 2008)
- Best Poster Award, Society of Chinese Bioscientists in America, 3-18-2017
- AFRRI Research Award, AFRRI, 2016
- Research and Development Achievements Award, U.S. Department of Army, U.S. Department of Defense, 2006
- DOD Female Science, Technology, Engineering, Mathematics Role Models, 2006
- Order of Military Medical Merit, 2006
- Outstanding Alumni Award 2005, Fu-Jen Catholic University, 2005
- The 20th Century Award for Achievement in Life Sciences, International Biographical Centre of Cambridge, England, 2000
Bibliography
- Kiang JG, Anderson MN, Smith JT. Ghrelin therapy sustains granulocyte colony-stimulating factor and keratinocyte factor to mitigate hematopoietic syndrome and spleen after whole-body ionizing irradiation combined with wound. Cell Biosci 8:27, 2018. doi: 10.1186/s13578-018-0225-3.
- Gorbunov NV, Kiang JG. Ghrelin therapy decreases incidents of intracranial hemorrhage in mice after whole-body ionizing irradiation combined with burn trauma. Int J Mol Sci 18(8). pii: E1693, 2017. doi: 10.3390/ijms18081693. PMID: 28771181
- Kiang JG, Smith JT, Anderson MN, Elliott TB, Gupta P, Balakathiresan N, Maheshwari RK, Knollmann-Ritschel B. Hemorrhage enhances cytokine, complement component 3, and caspase-3, and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury. PLoS ONE 12(9):e0184393, 2017. doi: 10.1371/journal.pone.0184393.PMID: 28934227
- Kiang JG, Smith JT, Anderson MN, Swift JM, Gupta P, Balakathiresan N, Maheshwari RK. Hemorrhage exacerbates radiation effects on survival, leukocytopenia, thrombopenia, erythropenia, bone marrow cell depletion and hematopoiesis, and inflammation-associated microRNAs expression in kidney. PLoS ONE 10:e0139271, 2015. doi: 10.1371/journal.pone.0139271. PMID: 26422254
- Swift JM, Smith JT, Kiang JG. Ciprofloxacin therapy mitigates ATP loss after irradiation combined with wound trauma: Preservation of pyruvate dehydrogenase and inhibition of pyruvate dehydrogenase kinase 1. Radiat Res 183: 684-692, 2015. PMID: 26010714
- Kiang JG, Gorbunov NV. Bone marrow mesenchymal stem cells increases survival after ionizing irradiation combined with wound trauma: Characterization and therapy. J Cell Sci Ther 5:190 (8 pages), 2014. doi: 10.4172/2157-7013.1000190
- Kiang JG, Zhai M, Liao P-J, Elliott TB, Gorbunov NV. Ghrelin therapy improves survival after whole-body ionizing irradiation combined with wound or burn: Amelioration of leukocytopenia, thrombopenia, splenomegaly, and bone marrow injury. Oxid Med Cell Longev 2014: 215858, 2014. doi: 10.1155/2014/215858. PMID: 25374650
- Fukumoto R, Burns TM, Kiang JG. Ciprofloxacin Enhances Stress Erythropoiesis in Spleen and Increases Survival after Whole-Body Irradiation Combined with Skin-Wound Trauma, PLoS One 9(2): e90448, 2014. doi: 10.1371/journal.pone.0090448. PMID: 24587369
- Kiang JG, Jiao W, Cary L, Mog SR, Elliott TB, Pellmar TC, Ledney GD. Wound trauma increases radiation-induced mortality by increasing iNOS, cytokine concentrations, and bacterial infections. Radiate Res 173: 319-332, 2010.
- Kiang JG, Krishnan S, Lu X, Li Y. Inhibition of inducible nitric oxide synthase protects human T cells from hypoxia-induced injury. Mol Pharmacol 73:738-747, 2008.
Robert L Kortum, M.D., Ph.D.
Name: Robert L Kortum, M.D., Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Assistant Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Cancer Cell Signaling
Ras
Email:
Office Phone:
(301) 295-3249
Department Website:
Education
Ph.D. - University of Nebraska Medical School, 2004
M.D. - University of Nebraska Medical School, 2006
M.D. - University of Nebraska Medical School, 2006
Bibliography
Biosketch Link:
Irwin Lucki, Ph.D.
Name: Irwin Lucki, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Professor and Chair
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Neuropharmacology
Antidepressant drugs
Email:
Office Phone:
(301) 295-3248
Education
Education: 1972 B.A. University of Illinois, Psychology
1976 M.A. University of Iowa, Psychology
1979 Ph.D. University of Iowa, Biopsychology
Postgraduate Training:
1979-1981 Postdoctoral Research Fellow, Psychopharmacology Training Program, Department of Psychiatry, University of Pennsylvania
1976 M.A. University of Iowa, Psychology
1979 Ph.D. University of Iowa, Biopsychology
Postgraduate Training:
1979-1981 Postdoctoral Research Fellow, Psychopharmacology Training Program, Department of Psychiatry, University of Pennsylvania
Biography
Selected from 180 publications:
Cryan, J.F., Valentino, R.J. and Lucki, I. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neuroscience and Biobehavioral Reviews, 2005, 29:547-569.
Valentino, R.J., Lucki, I. and Van Bockstaele, E. Corticotropin-releasing factor in the dorsal raphe nucleus: Linking stress coping and addiction. Brain Research, 2010, 1314:29-37. PMC2819581
Ho, N., Sommers, M.S. and Lucki, I. Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression. Neuroscience and Biobehavioral Reviews, 2013, 37:1346-1362. PMC3788092
Browne, C.A. and Lucki, I. Mechanisms mediating the antidepressant-like Lucki, I. The spectrum of behaviors influenced by serotonin. Biological Psychiatry, 1998, 44:151-162.
Page, M.E., Cryan, J.F., Sullivan, A., Dalvi, A. and Lucki, I. Behavioral and neurochemical effects of EMD 68843: A combined selective inhibitor of serotonin reuptake and partial 5-HT1A receptor agonist. Journal of Pharmacology and Experimental Therapeutics, 2002, 302:1-8.
Carr, G.V. and Lucki, I. The role of serotonin receptor subtypes in treating depression: A review of animal studies. Psychopharmacology, 2011, 213:265-287. PMC3374933
Carr, G.V., Schechter, L.E. and Lucki, I. Antidepressant and anxiolytic effects of
selective 5-HT6 receptor agonists in rats. Psychopharmacology, 2011, 213:499-507. PMC2910165
effects of ketamine: Screening for fast-acting novel antidepressants. Frontiers in Neuropharmacology, 2013, 4:161, 1-18. PMC3873522.
Mayorga, A.J., Dalvi, A., Page, M.E., Zimov-Levinson, S., Hen R. and Lucki, I. Antidepressant-like behavioral effects in 5-HT1A and 5-HT1B receptor mutant mice. Journal of Pharmacology and Experimental Therapeutics, 2001, 298:1101-1107.
Cryan, J.F., O’Leary, O.F., Jin, S.-H., Friedland, J.C., Ouyang, M., Hirsch, B.R., Page, M.E., Dalvi, A., Thomas, S.A. and Lucki, I. Norepinephrine deficient mice lack responses to antidepressant drugs, including SSRIs. Proceedings of the National Academy of Sciences, 2004, 101:8186-8191.
O’Leary, O.F., Bechtholt, A.J., Crowley, J.J., Valentino, R.J. and Lucki, I. The role of noradrenergic tone in the dorsal raphe nucleus of the mouse in the acute behavioral effects of antidepressant drugs. European Neuropsychopharmacology, 2007, 17:215-226.
Balu, D.T., Turner, J.R., Brookshire, B.R., Hill, T.E., Blendy, J.A. and Lucki, I. Brain monoamines and responses to antidepressant drugs in MRL/MpJ versus C57BL/6J and mice. Neuropharmacology, 2013, 67:503-510. PMC437180
Cryan, J.F., Markou, A. and Lucki, I. Assessing antidepressant-like activity in laboratory animals: Recent developments and future needs. Trends in Pharmacological Sciences, 2002, 23(5): 238-245.
Crowley, J.J. and Lucki, I. Opportunities to discover genes regulating depression and antidepressant response from rodent behavioral genetics. Current Pharmaceutical Design, 11:157-169, 2005.
Bechtholt, A.J., Valentino, R.J. and Lucki, I. Overlapping and distinct brain regions associated
with the anxiolytic effects of chlordiazepoxide and chronic fluoxetine. Neuropsychopharmacology, 2008, 33:2117-2130.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Price, M. L., Curtis, A.L., Kirby, L.G., Valentino, R.J. and Lucki, I. Biphasic effects of corticotropin-releasing factor on brain serotonergic activity. Neuropsychopharmacology, 1998, 18:492-502.
Price, M.L. and Lucki, I. Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor. Journal of Neuroscience, 2001, 21:2833-2841.
Howard, O., Carr, G.V., Hill, T.E., Valentino, R.J. and Lucki, I. Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin. Psychopharmacology, 2008, 199:569-82. PMC2744742
Snyder, K.P., Hill-Smith, T.E., Lucki, I. and Valentino, R.J. Corticotropin-releasing factor in the rat dorsal raphe nucleus promotes different forms of behavioral flexibility depending on social stress history. Neuropsychopharmacology, 2015, 40:2517-25. PMCID in process.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Falcon, E., Maier, K., Robinson, S.A. and Lucki, I. Effects of buprenorphine on behavioral tests for antidepressant and anxiolytic drugs in mice. Psychopharmacology, 2015, 232:907-915. PMC4326609
Browne, C.A., van Nest, D. and Lucki, I. Antidepressant-like effects of buprenorphine in rats are strain dependent. Behavioural Brain Research, 2015, 278:385-392. PMC4382376
Falcon, E., Browne, C.A., Leon, R.M., Fleites, V.C., Sweeney, R., Kirby, L.G. and Lucki, I. Antidepressant-like effects of buprenorphine are mediated by kappa opioid receptors. Neuropsychopharmacology, 2016, 41(9):2344-2351. PMC4946065
A full bibliography of over 170 peer-reviewed publications is available at: http://www.ncbi.nlm.nih.gov/sites/myncbi/irwin.lucki.1/bibliography/45296221/public/?sort=date&direction=ascending.
Cryan, J.F., Valentino, R.J. and Lucki, I. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neuroscience and Biobehavioral Reviews, 2005, 29:547-569.
Valentino, R.J., Lucki, I. and Van Bockstaele, E. Corticotropin-releasing factor in the dorsal raphe nucleus: Linking stress coping and addiction. Brain Research, 2010, 1314:29-37. PMC2819581
Ho, N., Sommers, M.S. and Lucki, I. Effects of diabetes on hippocampal neurogenesis: Links to cognition and depression. Neuroscience and Biobehavioral Reviews, 2013, 37:1346-1362. PMC3788092
Browne, C.A. and Lucki, I. Mechanisms mediating the antidepressant-like Lucki, I. The spectrum of behaviors influenced by serotonin. Biological Psychiatry, 1998, 44:151-162.
Page, M.E., Cryan, J.F., Sullivan, A., Dalvi, A. and Lucki, I. Behavioral and neurochemical effects of EMD 68843: A combined selective inhibitor of serotonin reuptake and partial 5-HT1A receptor agonist. Journal of Pharmacology and Experimental Therapeutics, 2002, 302:1-8.
Carr, G.V. and Lucki, I. The role of serotonin receptor subtypes in treating depression: A review of animal studies. Psychopharmacology, 2011, 213:265-287. PMC3374933
Carr, G.V., Schechter, L.E. and Lucki, I. Antidepressant and anxiolytic effects of
selective 5-HT6 receptor agonists in rats. Psychopharmacology, 2011, 213:499-507. PMC2910165
effects of ketamine: Screening for fast-acting novel antidepressants. Frontiers in Neuropharmacology, 2013, 4:161, 1-18. PMC3873522.
Mayorga, A.J., Dalvi, A., Page, M.E., Zimov-Levinson, S., Hen R. and Lucki, I. Antidepressant-like behavioral effects in 5-HT1A and 5-HT1B receptor mutant mice. Journal of Pharmacology and Experimental Therapeutics, 2001, 298:1101-1107.
Cryan, J.F., O’Leary, O.F., Jin, S.-H., Friedland, J.C., Ouyang, M., Hirsch, B.R., Page, M.E., Dalvi, A., Thomas, S.A. and Lucki, I. Norepinephrine deficient mice lack responses to antidepressant drugs, including SSRIs. Proceedings of the National Academy of Sciences, 2004, 101:8186-8191.
O’Leary, O.F., Bechtholt, A.J., Crowley, J.J., Valentino, R.J. and Lucki, I. The role of noradrenergic tone in the dorsal raphe nucleus of the mouse in the acute behavioral effects of antidepressant drugs. European Neuropsychopharmacology, 2007, 17:215-226.
Balu, D.T., Turner, J.R., Brookshire, B.R., Hill, T.E., Blendy, J.A. and Lucki, I. Brain monoamines and responses to antidepressant drugs in MRL/MpJ versus C57BL/6J and mice. Neuropharmacology, 2013, 67:503-510. PMC437180
Cryan, J.F., Markou, A. and Lucki, I. Assessing antidepressant-like activity in laboratory animals: Recent developments and future needs. Trends in Pharmacological Sciences, 2002, 23(5): 238-245.
Crowley, J.J. and Lucki, I. Opportunities to discover genes regulating depression and antidepressant response from rodent behavioral genetics. Current Pharmaceutical Design, 11:157-169, 2005.
Bechtholt, A.J., Valentino, R.J. and Lucki, I. Overlapping and distinct brain regions associated
with the anxiolytic effects of chlordiazepoxide and chronic fluoxetine. Neuropsychopharmacology, 2008, 33:2117-2130.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Price, M. L., Curtis, A.L., Kirby, L.G., Valentino, R.J. and Lucki, I. Biphasic effects of corticotropin-releasing factor on brain serotonergic activity. Neuropsychopharmacology, 1998, 18:492-502.
Price, M.L. and Lucki, I. Regulation of serotonin release in the lateral septum and striatum by corticotropin-releasing factor. Journal of Neuroscience, 2001, 21:2833-2841.
Howard, O., Carr, G.V., Hill, T.E., Valentino, R.J. and Lucki, I. Differential blockade of CRF-evoked behaviors by depletion of norepinephrine and serotonin. Psychopharmacology, 2008, 199:569-82. PMC2744742
Snyder, K.P., Hill-Smith, T.E., Lucki, I. and Valentino, R.J. Corticotropin-releasing factor in the rat dorsal raphe nucleus promotes different forms of behavioral flexibility depending on social stress history. Neuropsychopharmacology, 2015, 40:2517-25. PMCID in process.
Carr, G.V., Bangasser, D.A., Bethea, T., Young, M., Valentino, R.J. and Lucki, I. Antidepressant-like effects of kappa opioid receptor antagonists in Wistar-Kyoto rats. Neuropsychopharmacology, 2010, 35(3):752-63. PMC2813986
Falcon, E., Maier, K., Robinson, S.A. and Lucki, I. Effects of buprenorphine on behavioral tests for antidepressant and anxiolytic drugs in mice. Psychopharmacology, 2015, 232:907-915. PMC4326609
Browne, C.A., van Nest, D. and Lucki, I. Antidepressant-like effects of buprenorphine in rats are strain dependent. Behavioural Brain Research, 2015, 278:385-392. PMC4382376
Falcon, E., Browne, C.A., Leon, R.M., Fleites, V.C., Sweeney, R., Kirby, L.G. and Lucki, I. Antidepressant-like effects of buprenorphine are mediated by kappa opioid receptors. Neuropsychopharmacology, 2016, 41(9):2344-2351. PMC4946065
A full bibliography of over 170 peer-reviewed publications is available at: http://www.ncbi.nlm.nih.gov/sites/myncbi/irwin.lucki.1/bibliography/45296221/public/?sort=date&direction=ascending.
Representative publications, projects, and/or deployments
- 2007 - present, Principal Field Editor, Psychopharmacology
- 1995 - present, Editorial Advisory Board, Neuropsychopharmacology
- 2014 – present, Editorial Advisory Board, Neurobiology of Stress
- Buprenorphine for Depression and Anxiety.PI. NIMH, R01 MH92412, 2012-2018. Total direct costs = $1,250,000. The goal of this grant is to examine animal models supporting the development of buprenorphine for the clinical treatment of depression and anxiety.
- Kappa Receptor Antagonists as Rapid Acting Antidepressants. PI. NIMH, R01 MH105623, 2016-2020. Total direct costs = $1,000,000. The goal of this grant is to study animal models supporting the development of novel kappa receptor antagonists for the clinical treatment of mood disorders.
- Training Program in Neuropsychopharmacology. NIMH, T32 MH14654-34-38, 1978-2021. I was Training Program Director at the University of Pennsylvania 1992-2016.
- Regulation of Hippocampal Neurogenesis by Antidepressants. PI. NIMH, R01 MH86599, 2009-2015.
- Biology of Serotonin in Brain; Program Project Grant: Irwin Lucki, Ph.D., Program Director (1994-2007). NIMH, PO1-MH-48125.
- Regulation of Neurogenesis by Stress and Antidepressants. Program Director. National Cooperative Drug Discovery Group involving University of Pennsylvania and Wyeth Neuroscience. U01-MH 72832, 2005-2009.
Bibliography
- 2016- present Professor (with tenure) and Chair, Department of Pharmacology and Molecular Therapeutics, Uniformed University of the Health Sciences, Bethesda MD
- 2016-present Professor, Department of Psychiatry, Uniformed University of the Health Sciences, Bethesda MD
- 1996-2016 Professor of Psychology in Psychiatry (with tenure), Depts. of Psychiatry and Pharmacology, University of Pennsylvania, Philadelphia PA
- 1990-1996 Associate Professor of Psychology in Psychiatry (with tenure), Depts. of Psychiatry and Pharmacology, University of Pennsylvania, Philadelphia PA
- 1989-1990 Assistant Professor, Department of Pharmacology, University of Pennsylvania, Philadelphia PA
- 1984-1990 Assistant Professor of Psychology in Psychiatry, Department of Psychiatry, University of Pennsylvania, Philadelphia PA
- 1981-1984 Research Associate, Department of Psychiatry, University of Pennsylvania, Philadelphia PA
Fereshteh S. Nugent, Ph.D.
Name: Fereshteh S. Nugent, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
USU faculty
Faculty Rank:
Associate Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Synaptic plasticity, Reward Pathway, Addiction Neuorpsychiatric Disorders
Novel Anidepressants
Email:
Office Phone:
(301) 295-3243
Department Website:
Education
Ph.D., Neurophysiology, Tarbiat Modarres University, Tehran, Iran, 2003
Postdoctoral, Neuroscience, Brown University
Postdoctoral, Neuroscience, Brown University
Biography
Synaptic Plasticity of the Reward Pathway
Since the discovery of synaptic plasticity as the cellular correlate of learning and memory, strong overlaps between neural and cellular substrates of learning, drug addiction and stress-related disorders have been recognized. Yet it remains a major challenge to identify the neural circuits and synaptic mechanisms contributing to abnormalities in dopamine signaling induced by addictive drugs and adverse early life experiences. The major focus of my laboratory is the elucidation of synaptic mechanisms underlying reward learning, drug addiction and neuropsychiatric disorders such as depression, with particular emphasis on the midbrain dopamine system originating from the ventral tegmental area (VTA) and its control by the lateral habenula (LHb). Research in our laboratory also explores effects of severe early life stress on synaptic transmission and plasticity of distinct VTA dopamine circuits to identify the neural circuits and molecular mechanisms contributing to abnormalities in dopamine signaling induced by adverse early life experiences. To achieve these goals, we use a combination of immunohistochemical, biochemical, epigenetic, electrophysiological and behavioral techniques. We expect that identifying novel epigenetic mechanisms in the regulation of synaptic plasticity and memory formation in midbrain dopamine circuits will point to new directions in pharmacotherapy for drug addiction and stress-related disorders.
Selected Publications
Authement M.E., L. L. D., Shepard R.D., Browne C.A., Lucki L., Kassis H., Nugent F.S., A role for corticotrophin releasing factor signaling in the lateral habenula and its modulation by early life stress, Science Signaling, 11(520) (2018), Featured as the cover story
Summary: http://stke.sciencemag.org/cgi/content/summary/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Abstract: http://stke.sciencemag.org/cgi/content/abstract/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Reprint: http://stke.sciencemag.org/cgi/reprint/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Full text: http://stke.sciencemag.org/cgi/content/full/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Langlois, L.D. and Nugent F.S. Opiates and plasticity in ventral tegmental area, Invited Review, ACS Chemical Neuroscience, 20;8(9):1830-1838 (2017)
Authement M.E., Kodangattil J.N.,Gouty,S., Rusnak, M., Symes A.J., Cox B.M., and Nugent F.S., Histone deacetylase inhibition rescues maternal deprivation-induced GABAergic metaplasticity through restoration of AKAP signaling, Neuron, 86: 1240–1252 (2015)
Kodangattil J.N., Dacher M.A., Authement, M.E. and Nugent F.S., Spike timing-dependent plasticity at GABAergic synapses in the Ventral tegmental area. Journal of Physiology, 591.19: 4699-710 (2013)
Dacher, M. A., Gouty, S., Dash, S., Cox, B.M., and Nugent, F.S., A-kinase anchoring protein-calcineurin signaling in long-term depression of GABAergic synapses, Journal of Neuroscience, 33:2650-60 (2013)
Nugent, F.S., Penick, E.C., Kauer, J.A., Opiates block long-term potentiation of GABAergic synapses. Nature, 466: 1086-1095 (2007)
Postdoctoral Fellows: Dr. Ludovic Langlois
Graduate Students: Ryan Shepard
Lab Alumni: Dr. Matthieu Dacher (Université Pierre et Marie Curie, France), Dr. Jayaraj N. Kodangattil, Dr. Haifa Kassis, Dr. Michael Authement (NIAAA) and Steven Dash
Since the discovery of synaptic plasticity as the cellular correlate of learning and memory, strong overlaps between neural and cellular substrates of learning, drug addiction and stress-related disorders have been recognized. Yet it remains a major challenge to identify the neural circuits and synaptic mechanisms contributing to abnormalities in dopamine signaling induced by addictive drugs and adverse early life experiences. The major focus of my laboratory is the elucidation of synaptic mechanisms underlying reward learning, drug addiction and neuropsychiatric disorders such as depression, with particular emphasis on the midbrain dopamine system originating from the ventral tegmental area (VTA) and its control by the lateral habenula (LHb). Research in our laboratory also explores effects of severe early life stress on synaptic transmission and plasticity of distinct VTA dopamine circuits to identify the neural circuits and molecular mechanisms contributing to abnormalities in dopamine signaling induced by adverse early life experiences. To achieve these goals, we use a combination of immunohistochemical, biochemical, epigenetic, electrophysiological and behavioral techniques. We expect that identifying novel epigenetic mechanisms in the regulation of synaptic plasticity and memory formation in midbrain dopamine circuits will point to new directions in pharmacotherapy for drug addiction and stress-related disorders.
Selected Publications
Authement M.E., L. L. D., Shepard R.D., Browne C.A., Lucki L., Kassis H., Nugent F.S., A role for corticotrophin releasing factor signaling in the lateral habenula and its modulation by early life stress, Science Signaling, 11(520) (2018), Featured as the cover story
Summary: http://stke.sciencemag.org/cgi/content/summary/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Abstract: http://stke.sciencemag.org/cgi/content/abstract/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Reprint: http://stke.sciencemag.org/cgi/reprint/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Full text: http://stke.sciencemag.org/cgi/content/full/sigtrans;11/520/eaan6480?ijkey=HdDvVlA/ZsP76&keytype=ref&siteid=sigtrans
Langlois, L.D. and Nugent F.S. Opiates and plasticity in ventral tegmental area, Invited Review, ACS Chemical Neuroscience, 20;8(9):1830-1838 (2017)
Authement M.E., Kodangattil J.N.,Gouty,S., Rusnak, M., Symes A.J., Cox B.M., and Nugent F.S., Histone deacetylase inhibition rescues maternal deprivation-induced GABAergic metaplasticity through restoration of AKAP signaling, Neuron, 86: 1240–1252 (2015)
Kodangattil J.N., Dacher M.A., Authement, M.E. and Nugent F.S., Spike timing-dependent plasticity at GABAergic synapses in the Ventral tegmental area. Journal of Physiology, 591.19: 4699-710 (2013)
Dacher, M. A., Gouty, S., Dash, S., Cox, B.M., and Nugent, F.S., A-kinase anchoring protein-calcineurin signaling in long-term depression of GABAergic synapses, Journal of Neuroscience, 33:2650-60 (2013)
Nugent, F.S., Penick, E.C., Kauer, J.A., Opiates block long-term potentiation of GABAergic synapses. Nature, 466: 1086-1095 (2007)
Postdoctoral Fellows: Dr. Ludovic Langlois
Graduate Students: Ryan Shepard
Lab Alumni: Dr. Matthieu Dacher (Université Pierre et Marie Curie, France), Dr. Jayaraj N. Kodangattil, Dr. Haifa Kassis, Dr. Michael Authement (NIAAA) and Steven Dash
Frank Shewmaker, Ph.D.
Name: Frank Shewmaker, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Assistant Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Molecular and Cell Biology Graduate Program
Email:
Office Phone:
(301) 295-3527
Education
B.S., Biochemistry, Auburn University
Ph.D., Biochemistry, Tulane University
Post-Doctoral Training, Laboratory of Biochemistry & Genetics, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health (NIH)
Ph.D., Biochemistry, Tulane University
Post-Doctoral Training, Laboratory of Biochemistry & Genetics, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health (NIH)
Bibliography
Biosketch Link:
Vijay K. Singh, Ph.D.
Name: Vijay K. Singh, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Prof.
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Radiation Biology
Countermeasures
Email:
Office Phone:
(301) 295-2347
Department Website:
Education
1983 Ph.D., Central Drug Research Institute (KU), India
1978 M.Sc., Kanpur University, India
1975 B.Sc., Magadh University, India
1978 M.Sc., Kanpur University, India
1975 B.Sc., Magadh University, India
Biography
Mechanism of radiation injury and advanced development of radiation countermeasures
My laboratory focuses attention on the molecular basis of radiation injury which results in acute radiation syndromes (ARS), and the mechanism of action of potential radiation countermeasures. Our ultimate goal is to develop radiation countermeasures to protect military personnel, first responders and civilians from succumbing to ARS following radiation exposure whether it is accidental or as a result of deliberate attack. To achieve this goal we are currently investigating the mechanism of action of gamma-tocotrienol (GT3, an isomer of Vitamin E), Ex-RAD (a chlorobenzylsulphone derivative), toll-like receptor (TLR) ligands (CBLB502), and anti-ceramide antibody at the cellular level, by evaluating cell signaling pathways (cytokine expression, p53 pathway, TLR activation) including DNA damage and repair pathways.
In collaboration with corporate partners, my lab is developing several radiation countermeasures which are under advanced stages of development. CBLB502 and anti-cermide antibody appear to be promising. Ex-RAD has been shown to have both radioprotective and radiomitigative properties. Ex-RAD protects the hematopoietic system and is able to increase survival of irradiated mice by alleviating the severe radiation induced pancytopenia and restoring select bone marrow functions through the up-regulation of the PI3-kinase/AKT pathways and pathways involved with the DNA damage response and DNA repair. Ex-RAD studies have received significant funding from DMRDP (DoD) and BARDA (HHS).
My lab is also working to develop GT3, as a radiation countermeasure in collaboration with Prof. Martin Hauer-Jensen. It has shown great promise in rodent model, capable of mobilizing progenitors, and its radioprotective efficacy is mediated through G-CSF in murine model. Recently, we found that a single administration of GT3, without additional support (fluids, antibiotics, blood products, etc.), was just as effective as multiple administrations of G-CSF, the current gold standard of radiation countermeasures approved by US FDA, with full support. Based on the promising results of our pilot study using the large animal model, we have received funding from CDMRP (DoD) for the advanced development of GT3.
Additionally, we are working to develop a novel anti-ceramide antibody in collaboration with Prof. Richard Kolesnick of Sloan Kettering and Ceramide Theraprutics as a radiation countermeasure, capable of being administered prior to or after radiation exposure. Studies have indicated that this potential countermeasure inhibits ceramide-mediated endothelial apoptosis, which provides significant protection against radiation induced, potentially fatal, gastrointestinal syndrome. Additional studies have shown that a single chain variable fragment of the full length antibody molecule is effective in doses one tenth of the full length version. This project had been supported by DMRDP (DoD). Additional countermeasures being investigated are CBLB612, CBLB613, and myeloid progenitors in collaboration with various academic and corporate partners with support from various funding agencies such as BARDA, NIAID, JPC7, CDMRP, and DMRDP.
My laboratory focuses attention on the molecular basis of radiation injury which results in acute radiation syndromes (ARS), and the mechanism of action of potential radiation countermeasures. Our ultimate goal is to develop radiation countermeasures to protect military personnel, first responders and civilians from succumbing to ARS following radiation exposure whether it is accidental or as a result of deliberate attack. To achieve this goal we are currently investigating the mechanism of action of gamma-tocotrienol (GT3, an isomer of Vitamin E), Ex-RAD (a chlorobenzylsulphone derivative), toll-like receptor (TLR) ligands (CBLB502), and anti-ceramide antibody at the cellular level, by evaluating cell signaling pathways (cytokine expression, p53 pathway, TLR activation) including DNA damage and repair pathways.
In collaboration with corporate partners, my lab is developing several radiation countermeasures which are under advanced stages of development. CBLB502 and anti-cermide antibody appear to be promising. Ex-RAD has been shown to have both radioprotective and radiomitigative properties. Ex-RAD protects the hematopoietic system and is able to increase survival of irradiated mice by alleviating the severe radiation induced pancytopenia and restoring select bone marrow functions through the up-regulation of the PI3-kinase/AKT pathways and pathways involved with the DNA damage response and DNA repair. Ex-RAD studies have received significant funding from DMRDP (DoD) and BARDA (HHS).
My lab is also working to develop GT3, as a radiation countermeasure in collaboration with Prof. Martin Hauer-Jensen. It has shown great promise in rodent model, capable of mobilizing progenitors, and its radioprotective efficacy is mediated through G-CSF in murine model. Recently, we found that a single administration of GT3, without additional support (fluids, antibiotics, blood products, etc.), was just as effective as multiple administrations of G-CSF, the current gold standard of radiation countermeasures approved by US FDA, with full support. Based on the promising results of our pilot study using the large animal model, we have received funding from CDMRP (DoD) for the advanced development of GT3.
Additionally, we are working to develop a novel anti-ceramide antibody in collaboration with Prof. Richard Kolesnick of Sloan Kettering and Ceramide Theraprutics as a radiation countermeasure, capable of being administered prior to or after radiation exposure. Studies have indicated that this potential countermeasure inhibits ceramide-mediated endothelial apoptosis, which provides significant protection against radiation induced, potentially fatal, gastrointestinal syndrome. Additional studies have shown that a single chain variable fragment of the full length antibody molecule is effective in doses one tenth of the full length version. This project had been supported by DMRDP (DoD). Additional countermeasures being investigated are CBLB612, CBLB613, and myeloid progenitors in collaboration with various academic and corporate partners with support from various funding agencies such as BARDA, NIAID, JPC7, CDMRP, and DMRDP.
Representative publications, projects, and/or deployments
- G1B23687 Determination of radiation dose response for the AFRRI LINAC and subsequent non-clinical studies to evaluate potential medical countermeasures as mitigators of hematopoietic and/or low dose GI syndromes (H-ARS; GI-ARS) in an NHP model. Biomedical Advanced Research and Development Authority (BARDA), $8,535,865, September 15, 2015 – September 14, 2019
- G1B22927 Advanced development of gamma-tocotrienol as a radiation countermeasure. Congressionally Directed Medical Research Programs (CDMRP), $7,811,978, September 21, 2015 – September 20, 2019.
- G2B2HF Evaluation of radiation mitigators in nonhuman primates with supportive care. National Institute of Allergy and Infectious Diseases (NIAID), FY 2016 $406,581, FY 2017 $1,264,698, September 2015 – Sepetember 2017, Open ended, yearly renewal expected every year with additional budget.
- NAB22586 Advanced development of Ex-RAD as a radiomitigator. Defense Medical Research and Development Program (DMRDP), $ 1,198,000, April 2014 – September 2017
- G1B24024 Advanced Development of BIO 300 for Acute Radiation Syndrome and Delayed Effects of Acute Radiation Exposure, Congressionally Directed Medical Research Programs (CDMRP), $1,195,189, October 2016 – September 2019
- RAB24402 Biomarkers for radiation injury: Integrative omics study, AFRRI, $240,000, November 11, 2016 – September 30, 2019
- AFR-B2-4365 Development of Bio 301: An encapsulated nano-genistein therapy, Congressionally Directed Medical Research Programs (CDMRP), $712,295, POP to be negotiated
Bibliography
Biosketch Link:
- Singh VK, Seed TM: A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures. Int J Radiat Biol (in press: DOI: 10.1080/09553002.2017.1332438), 2017.
- Singh VK, Garcia M, Seed TM: A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status. Int J Radiat Biol (in press: DOI: 10.1080/09553002.2017.1338782), 2017.
- Singh VK, Hanlon BK, Santiago PT, Seed TM: A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: Part III. Countermeasures under early stages of development along with ‘standard of care’ medicinal and procedures not requiring regulatory approval for use. Int J Radiat Biol (in press: DOI: 10.1080/09553002.2017.1332440), 2017.
- Fendler W, Malachowska B, Meghani K, Konstantinopoulos PA, Guha C, Singh VK, Chowdhury C: Evolutionarily conserved serum microRNAs can predict radiation-induced fatality in non-human primates. Sci Transl Med 9:eaal2408, 2017
- Singh VK, Fatanmi OO, Wise SY, Newman VL, Romaine PLP, Seed TM: The potentiation of the radioprotective efficacy of two medical countermeasures, gamma-tocotrienol and amifostine, by a combination prophylactic modality. Radiat Prot Dosimetry 172:302-310, 2016.
- Singh VK, Kulkarni S, Fatanmi OO, Wise SY, Newman VL, Romaine PLP, Hendrickson H, Gulani J, Ghosh SP, Kumar KS, Hauer-Jensen M: Radioprotective efficacy of gamma-tocotrienol in nonhuman primates. Radiat Res 185:285-298, 2016.
- Krivokrysenko VI, Toshkov I, Gleiberman A, Krasnov P, Shyshynova I, Bespalov I, Maitra R, Narizhneva N, Singh VK, Whitnall MH, Purmal A, Shakhov A, Gudkov A, Feinstein E: TLR5 agonist Entolimod mitigates acute radiation syndrome in non-human primates. PLoS One 10:e0135388, 2015.
- Elliott TB, Bolduc DL, Ledney GD, Kiang JG, Fatanmi OO, Wise SY, Romaine PLP, Newman VL, Singh VK: Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in mice exposed to radiation and combined injury. Int J Radiat Biol 91:690-702, 2015.
- Dalgard CL, Jacobowitz DM, Singh VK, Saleem KS, Ursano RJ, Starr JM, Pollard HB: A novel analytical brain block tool to enable functional annotation of discriminatory transcript biomarkers among discrete regions of the fronto-limbic circuit in primate brain. Brain Res 1600:42-58, 2015.
- Singh VK, Wise SY, Fatanmi OO, Scott J, Romaine PLP, Newman VL, Verma A, Elliott TB, Seed TM: Progenitors mobilized by gamma-tocotrienol as an effective radiation countermeasure. PLoS ONE 9:e114078, 2014.
Andrew L Snow, Ph.D.
Name: Andrew L Snow, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Associate Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
human immunology, lymphocyte signaling & apoptosis, primary immune disorders
Email:
Office Phone:
(301) 295-3267
Education
B.S., Biology, Visual Arts, Duke University
Ph.D., Immunology, Stanford University School of Medicine
Postdoctoral Training, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH
Ph.D., Immunology, Stanford University School of Medicine
Postdoctoral Training, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, NIH
Biography
RESEARCH INTERESTS
The major emphasis of my laboratory is to elucidate how aberrations in lymphocyte signaling contribute to deranged immune homeostasis in novel lymphoproliferative disorders and primary immunodeficiencies. Our research focuses on identifying novel molecular regulators of lymphocyte apoptosis and differentiation in humans, with the ultimate goal of informing new therapeutic approaches for controlling immune responses by manipulating cell death sensitivity.
ONGOING PROJECTS
1. Signal regulation and physiological relevance of specific T cell apoptosis pathways
The regulation and eventual contraction of activated T cells during an immune response is critical for maintaining equilibrium in the immune system and preventing unwanted damage to host tissues. Normally, specific apoptosis programs induced by T cell receptor (TCR) restimulation or cytokine withdrawal work to cull the majority of activated effector T cells, leaving a small pool of memory T cells behind to protect against subsequent infections (Fig 1). We now appreciate that genetic defects in lymphocyte apoptosis directly contribute to excess lymphoproliferation in humans. For example, T cells from patients with X-linked lymphoproliferative disease (XLP-1) display a profound defect in T cell receptor restimulation-induced cell death (RICD; also known as activation-induced cell death), a critical self-regulatory apoptosis program that constrains effector T cell expansion. Our lab has defined several biochemical mechanisms by which signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), which is lost or mutated in XLP patients, facilitates RICD. Most recently, we led an international collaborative effort demonstrating that inhibition of diacylglycerol kinase alpha (DGKa), a modulatory enzyme with elevated activity in SAP-deficient T cells, presents a viable therapeutic approach for treating EBV-induced fulminant mononucleosis in XLP-1 patients, via restoration of RICD. Collectively, this work underscores the physiological relevance of RICD in preventing excessive T cell accumulation, severe immunopathology and mortality in XLP patients infected with EBV. We continue to investigate how RICD sensitivity is “tuned” via SAP-dependent signals.
We are also investigating novel links between metabolic programming and apoptosis sensitivity in human T cells. Our recent work indicates that while excessive anabolic metabolism (i.e. glycolysis) leaves effector T cells more susceptible to RICD, catabolic metabolism (i.e. autophagy) can protect T cells derived from distinct memory compartments from death induced by cytokine withdrawal. We have delineated specific molecular mechanisms responsible for these changes in cell death sensitivity, and continue to investigate how specific metabolic programs affect T cell viability. Our work illuminates how metabolic changes govern T cell survival, and may explain why certain memory T cells give rise to a larger, more robust effector response (via reduced cell death) that better protects the host when challenged with a pathogen or tumor.
2. Novel immunological disorders linked to mutations in CARD11
We discovered that gain-of-function (GOF) mutations in the CARD11 gene cause a rare congenital B cell lymphoproliferative disorder called B cell Expansion with NF-kB and T cell Anergy (BENTA) disease. My laboratory has taken a leading role in the genetic diagnosis and phenotypic characterization of an expanding cohort of BENTA patients (Fig 2). CARD11 encodes a scaffolding protein that links antigen receptor signaling to NF-kB activation in lymphocytes. Unlike the wild-type protein, CARD11 GOF mutants spontaneously oligomerize and drive constitutive activation of NF-kB, contributing to increased proliferation and enhanced survival of both immature and naïve patient B cells. Surprisingly, BENTA patients also exhibit hallmarks of immunodeficiency, including B cell differentiation defects, selective antibody deficiency, and opportunistic viral infections (e.g. molluscum contagiousum, chronic EBV) that reflect impaired T cell responses. Our latest findings pinpoint intrinsic molecular defects in plasma cell differentiation and antibody secretion in activated BENTA patient B cells, despite profound apoptosis resistance that likely explains excessive B cell expansion.
In collaboration with Dr. Joshua Milner (NIH) and others, we are also investigating loss-of-function (LOF) CARD11 mutations in atopic patients with severe eczema. We recently described 4 families with distinct, hypomorphic CARD11 mutations that dominantly interfere with WT CARD11 signaling, resulting in impaired NF-kB and mTORC1 signaling. Extensive structure-function studies of the CARD11 molecule continue in my lab, drawing from an expanding list of natural mutations in human patients. Using cell transfection systems, murine models and primary patient lymphocytes, my lab also continues to investigate how both GOF and LOF CARD11 mutations perturb signaling, differentiation and function of B and T cells.
The major emphasis of my laboratory is to elucidate how aberrations in lymphocyte signaling contribute to deranged immune homeostasis in novel lymphoproliferative disorders and primary immunodeficiencies. Our research focuses on identifying novel molecular regulators of lymphocyte apoptosis and differentiation in humans, with the ultimate goal of informing new therapeutic approaches for controlling immune responses by manipulating cell death sensitivity.
ONGOING PROJECTS
1. Signal regulation and physiological relevance of specific T cell apoptosis pathways
The regulation and eventual contraction of activated T cells during an immune response is critical for maintaining equilibrium in the immune system and preventing unwanted damage to host tissues. Normally, specific apoptosis programs induced by T cell receptor (TCR) restimulation or cytokine withdrawal work to cull the majority of activated effector T cells, leaving a small pool of memory T cells behind to protect against subsequent infections (Fig 1). We now appreciate that genetic defects in lymphocyte apoptosis directly contribute to excess lymphoproliferation in humans. For example, T cells from patients with X-linked lymphoproliferative disease (XLP-1) display a profound defect in T cell receptor restimulation-induced cell death (RICD; also known as activation-induced cell death), a critical self-regulatory apoptosis program that constrains effector T cell expansion. Our lab has defined several biochemical mechanisms by which signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), which is lost or mutated in XLP patients, facilitates RICD. Most recently, we led an international collaborative effort demonstrating that inhibition of diacylglycerol kinase alpha (DGKa), a modulatory enzyme with elevated activity in SAP-deficient T cells, presents a viable therapeutic approach for treating EBV-induced fulminant mononucleosis in XLP-1 patients, via restoration of RICD. Collectively, this work underscores the physiological relevance of RICD in preventing excessive T cell accumulation, severe immunopathology and mortality in XLP patients infected with EBV. We continue to investigate how RICD sensitivity is “tuned” via SAP-dependent signals.
We are also investigating novel links between metabolic programming and apoptosis sensitivity in human T cells. Our recent work indicates that while excessive anabolic metabolism (i.e. glycolysis) leaves effector T cells more susceptible to RICD, catabolic metabolism (i.e. autophagy) can protect T cells derived from distinct memory compartments from death induced by cytokine withdrawal. We have delineated specific molecular mechanisms responsible for these changes in cell death sensitivity, and continue to investigate how specific metabolic programs affect T cell viability. Our work illuminates how metabolic changes govern T cell survival, and may explain why certain memory T cells give rise to a larger, more robust effector response (via reduced cell death) that better protects the host when challenged with a pathogen or tumor.
2. Novel immunological disorders linked to mutations in CARD11
We discovered that gain-of-function (GOF) mutations in the CARD11 gene cause a rare congenital B cell lymphoproliferative disorder called B cell Expansion with NF-kB and T cell Anergy (BENTA) disease. My laboratory has taken a leading role in the genetic diagnosis and phenotypic characterization of an expanding cohort of BENTA patients (Fig 2). CARD11 encodes a scaffolding protein that links antigen receptor signaling to NF-kB activation in lymphocytes. Unlike the wild-type protein, CARD11 GOF mutants spontaneously oligomerize and drive constitutive activation of NF-kB, contributing to increased proliferation and enhanced survival of both immature and naïve patient B cells. Surprisingly, BENTA patients also exhibit hallmarks of immunodeficiency, including B cell differentiation defects, selective antibody deficiency, and opportunistic viral infections (e.g. molluscum contagiousum, chronic EBV) that reflect impaired T cell responses. Our latest findings pinpoint intrinsic molecular defects in plasma cell differentiation and antibody secretion in activated BENTA patient B cells, despite profound apoptosis resistance that likely explains excessive B cell expansion.
In collaboration with Dr. Joshua Milner (NIH) and others, we are also investigating loss-of-function (LOF) CARD11 mutations in atopic patients with severe eczema. We recently described 4 families with distinct, hypomorphic CARD11 mutations that dominantly interfere with WT CARD11 signaling, resulting in impaired NF-kB and mTORC1 signaling. Extensive structure-function studies of the CARD11 molecule continue in my lab, drawing from an expanding list of natural mutations in human patients. Using cell transfection systems, murine models and primary patient lymphocytes, my lab also continues to investigate how both GOF and LOF CARD11 mutations perturb signaling, differentiation and function of B and T cells.
Bibliography
Biosketch Link:
- Voss K, Larsen SE, Snow AL. 2017. Metabolic reprogramming and apoptosis sensitivity: defining the contours of a T cell response. Cancer Letters 408:190-96.
- Arjunaraja S, Nosé BD, Sukumar G, Lott NM, Dalgard CL, Snow AL. 2017. Intrinsic Plasma Cell Differentiation Defects in BENTA Patient B Cells. Frontiers in Immunology 8: 913.
- Larsen SE, Voss K, Laing ED, Snow AL. 2017. Differential cytokine withdrawal-induced death sensitivity of effector T cells derived from distinct human CD8+ memory subsets. Cell Death Discovery 3:17031.
- Ma CA, Stinson JR, Zhang Y, Abbott JK, Weinreich MA, Hauk PJ, Reynolds PR, Lyons JJ, Nelson CG, Ruffo E, Dorjbal B, Glauzy S, Stoddard J, Niemela J, Rosenzweig SD, McElwee JJ, DiMaggio T, Stone KD, Palma A, Oleastro M, Prieto E, Bernasconi A, Dubra G, Danielian S, Zaiat J, Marti M, Kim B, Cooper MA, Romberg N, Meffre E, Gelfand EW*, Snow AL*, Milner JD*. 2017. “Germline hypomorphic CARD11 mutations in severe atopic disease.” Nature Genetics 49:1192-1201.
- Larsen SE, Bilenkin A, Snow AL. 2017. Sensitivity to restimulation-induced cell death is linked to glycolytic metabolism in human T cells. Journal of Immunology 198: 147-55.
- Ruffo E, Malacarne V, Larsen SE, Das R, Patrussi L, Wulfing C, Biskup C, Schwartzberg PL, Baldari TC, Rubio I, Nichols KE*, Snow AL*, Baldanzi G*, Graziani A*. 2016. Inhibition of diacylglycerol kinase alpha restores TCR-induced diacylglycerol signaling and restimulation-induced cell death in XLP-1 T lymphocytes. Science Translational Medicine 8: 321ra7.
- Brohl AS, Stinson JR, Su HC, Badgett T, Jennings CD, Sukumar G, Sindiri S, Wang W, Moir S, Dalgard CL, Moscow JA, Khan J, Snow AL. 2015. Germline CARD11 mutation in a patient with severe congenital B cell lymphocytosis. Journal of Clinical Immunology, 35: 32-46. ePub Oct 2014.
- Katz G, Krummey SM, Larsen SE, Stinson JR, Snow AL. 2014. SAP facilitates recruitment and activation of LCK at NTB-A receptors during restimulation-induced cell death. Journal of Immunology 192: 4202-9.
- Snow AL, Xiao W, Chaigne-Delalande B, Pittaluga S, Stinson JR, Matthews HF, Lu W, Zheng L, Schmitz R, Jhavar S, Kuchen S, Lamborn IT, Jing H, Raffeld M, Su HC, Staudt LM, Lenardo MJ. 2012. Congenital B cell lymphocytosis explained by novel germline CARD11 mutations. Journal of Experimental Medicine 209: 2247-61.
- Snow AL, Marsh RA, Krummey SM, Roehrs P, Young LR, Zhang K, van Hoff J, Dhar D, Nichols KE, Filipovich AH, Su HC, Bleesing JJ, Lenardo MJ. 2009. Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency. Journal of Clinical Investigation 119: 2976-2989.
Aviva J Symes, Ph.D.
Name: Aviva J Symes, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Traumatic brain injury
Role of renin angiotensin system in the brain after injury
Email:
Office Phone:
(301) 295-3234
Education
B.Sc.(Hons). Biochemistry, University of Manchester, UK
Ph.D. Biochemistry/Molecular Biology, University College London, UK
Post-doctoral training: Massachusetts General Hospital/ Harvard Medical School, Boston.
Ph.D. Biochemistry/Molecular Biology, University College London, UK
Post-doctoral training: Massachusetts General Hospital/ Harvard Medical School, Boston.
Biography
RESEARCH INTERESTS:
My lab aims to understand the mechanisms through which the brain responds to traumatic injury and more specifically to delineate the pathways through which detrimental neuroinflammatory cascades can be altered to enhance recovery after injury. The initial lesion can produce significant tissue damage and breakdown of the blood brain barrier. These immediate effects lead to activation of many secondary cascades involving interplay between endogenous surviving neurons and glia, and infiltrating cells and molecules from the bloodstream. Injury therefore leads to acute neuroinflammatory cascades, and also to more chronic inflammatory effects. Indeed, activated microglia have been documented in postmortem brains many years after the initial insult. Our lab focuses on understanding the molecular signaling cascades that occur after injury in addition to testing potential therapeutics to enhance recovery from injury. We currently utilize several different rodent models of traumatic brain injury (TBI), with assays ranging from behavioral through molecular to understand the complex interactions that occur after injury, and to determine how manipulations may impact on functional recovery. We also utilize primary cell cultures to tease apart the molecular signaling pathways that contribute to inflammation after injury.
Angiotensin receptor blockers as potential therapeutics for TBI
Angiotensin receptor blockers (ARBs) are widely used FDA-approved anti-hypertension drugs with a favorable side effect profile that have been used as a mechanism for reducing the amount of TGF-β signaling in several different organ systems. In the CNS, ARBs have also been shown to be neuroprotective, anti-inflammatory and protective of the cerebral blood flow (CBF). The brain possesses its own renin angiotensin system, with many different components of the system expressed in the different cell types in the brain. However, in addition to acting as antagonists at the Angiotensin II receptor 1 (AT1R) some ARBs also possess potent PPARγ agonist activity that enhances their anti-inflammatory action. We have demonstrated that the ARB candesartan, lessens inflammation, reduces lesion volume, limits glial reactivity, increases neuronal survival and improves motor and cognitive recovery up to 28 days after injury. These beneficial effects are seen when low-dose candesartan is administered up to 6 hours after injury, a clinically acceptable therapeutic window. Our data suggest that both AT1 receptor antagonism and PPARγ agonism contribute to the efficacy of ARB treatment after TBI and it is this multimodal action by a single drug that makes it a strong candidate for TBI clinical trials. We are pursuing translational studies for candesartan for brain injury in addition to investigating the consequences of TBI on the endogenous renin-angiotensin system in the brain.
TGF-β signaling after injury
TGF-β is an injury induced cytokine that has complex roles in the central nervous system. After brain injury TGF-β can promote astrogliosis and enhance the deposition of molecules inhibitory to regeneration in the glial scar. Yet TGF-β is also neuroprotective indicating the sometimes conflicting roles of this cytokine. We have shown that after a penetrating brain injury mice that lack expression of the TGF-β signaling molecule Smad3, form a glial scar more quickly, with a smaller scar, than wild type mice. However, we also found that Smad3 null mice have more pronounced neuronal loss after injury. Thus, global interference with TGF-β signaling is not a desirable therapeutic option. Further, TGF-β is anti-inflammatory in some contexts – so chronic repression of TGF-β signaling pathways may enhance inflammation. In primary microglial cultures we have shown that inflammatory pathways downregulate TGF-β receptor expression, allowing for prolonged enhancement of the inflammatory activated state.
My lab aims to understand the mechanisms through which the brain responds to traumatic injury and more specifically to delineate the pathways through which detrimental neuroinflammatory cascades can be altered to enhance recovery after injury. The initial lesion can produce significant tissue damage and breakdown of the blood brain barrier. These immediate effects lead to activation of many secondary cascades involving interplay between endogenous surviving neurons and glia, and infiltrating cells and molecules from the bloodstream. Injury therefore leads to acute neuroinflammatory cascades, and also to more chronic inflammatory effects. Indeed, activated microglia have been documented in postmortem brains many years after the initial insult. Our lab focuses on understanding the molecular signaling cascades that occur after injury in addition to testing potential therapeutics to enhance recovery from injury. We currently utilize several different rodent models of traumatic brain injury (TBI), with assays ranging from behavioral through molecular to understand the complex interactions that occur after injury, and to determine how manipulations may impact on functional recovery. We also utilize primary cell cultures to tease apart the molecular signaling pathways that contribute to inflammation after injury.
Angiotensin receptor blockers as potential therapeutics for TBI
Angiotensin receptor blockers (ARBs) are widely used FDA-approved anti-hypertension drugs with a favorable side effect profile that have been used as a mechanism for reducing the amount of TGF-β signaling in several different organ systems. In the CNS, ARBs have also been shown to be neuroprotective, anti-inflammatory and protective of the cerebral blood flow (CBF). The brain possesses its own renin angiotensin system, with many different components of the system expressed in the different cell types in the brain. However, in addition to acting as antagonists at the Angiotensin II receptor 1 (AT1R) some ARBs also possess potent PPARγ agonist activity that enhances their anti-inflammatory action. We have demonstrated that the ARB candesartan, lessens inflammation, reduces lesion volume, limits glial reactivity, increases neuronal survival and improves motor and cognitive recovery up to 28 days after injury. These beneficial effects are seen when low-dose candesartan is administered up to 6 hours after injury, a clinically acceptable therapeutic window. Our data suggest that both AT1 receptor antagonism and PPARγ agonism contribute to the efficacy of ARB treatment after TBI and it is this multimodal action by a single drug that makes it a strong candidate for TBI clinical trials. We are pursuing translational studies for candesartan for brain injury in addition to investigating the consequences of TBI on the endogenous renin-angiotensin system in the brain.
TGF-β signaling after injury
TGF-β is an injury induced cytokine that has complex roles in the central nervous system. After brain injury TGF-β can promote astrogliosis and enhance the deposition of molecules inhibitory to regeneration in the glial scar. Yet TGF-β is also neuroprotective indicating the sometimes conflicting roles of this cytokine. We have shown that after a penetrating brain injury mice that lack expression of the TGF-β signaling molecule Smad3, form a glial scar more quickly, with a smaller scar, than wild type mice. However, we also found that Smad3 null mice have more pronounced neuronal loss after injury. Thus, global interference with TGF-β signaling is not a desirable therapeutic option. Further, TGF-β is anti-inflammatory in some contexts – so chronic repression of TGF-β signaling pathways may enhance inflammation. In primary microglial cultures we have shown that inflammatory pathways downregulate TGF-β receptor expression, allowing for prolonged enhancement of the inflammatory activated state.
Bibliography
Biosketch Link:
- Bone morphogenetic protein-2-mediated pain and inflammation in a rat model of posterolateral arthrodesis. Mitchell K, Shah JP, Dalgard CL, Tsytsikova LV, Tipton AC, Dmitriev AE, Symes AJ. BMC neuroscience. 2016; 17(1):80. PubMed [journal]PMID: 27905881 PMCID: PMC5134101
- Neurorestoration after traumatic brain injury through angiotensin II receptor blockage. Villapol S, Balarezo MG, Affram K, Saavedra JM, Symes AJ. Brain : a journal of neurology. 2015; 138(Pt 11):3299-315. PubMed [journal]PMID: 26115674 PMCID: PMC4731413
- Runx1 promotes proliferation and neuronal differentiation in adult mouse neurosphere cultures. Logan TT, Rusnak M, Symes AJ. Stem cell research. 2015; 15(3):554-564. PubMed [journal]PMID: 26473321
- Hepatic expression of serum amyloid A1 is induced by traumatic brain injury and modulated by telmisartan. Villapol S, Kryndushkin D, Balarezo MG, Campbell AM, Saavedra JM, Shewmaker FP, Symes AJ. The American journal of pathology. 2015; 185(10):2641-52. PubMed [journal]PMID: 26435412 PMCID: PMC4607758
- . Temporal patterns of cortical proliferation of glial cell populations after traumatic brain injury in mice. Susarla BT, Villapol S, Yi JH, Geller HM, Symes AJ. ASN neuro. 2014; 6(3):159-70. PubMed [journal]PMID: 24670035 PMCID: PMC4013687
- LPS antagonism of TGF-β signaling results in prolonged survival and activation of rat primary microglia. Mitchell K, Shah JP, Tsytsikova LV, Campbell AM, Affram K, Symes AJ. Journal of neurochemistry. 2014; 129(1):155-68. PubMed [journal]PMID: 24251648
- Temporal dynamics of cerebral blood flow, cortical damage, apoptosis, astrocyte-vasculature interaction and astrogliosis in the pericontusional region after traumatic brain injury. Villapol S, Byrnes KR, Symes AJ. Frontiers in neurology. 2014; 5:82. PubMed [journal]PMID: 24926283 PMCID: PMC4044679
- Smad3 deficiency increases cortical and hippocampal neuronal loss following traumatic brain injury. Villapol S, Wang Y, Adams M, Symes AJ. Experimental neurology. 2013; 250:353-65. PubMed [journal]PMID: 24120438
- TGF-β superfamily gene expression and induction of the Runx1 transcription factor in adult neurogenic regions after brain injury. Logan TT, Villapol S, Symes AJ. PloS one. 2013; 8(3):e59250. PubMed [journal]PMID: 23555640 PMCID: PMC3605457
- Candesartan, an angiotensin II AT₁-receptor blocker and PPAR-γ agonist, reduces lesion volume and improves motor and memory function after traumatic brain injury in mice. Villapol S, Yaszemski AK, Logan TT, Sánchez-Lemus E, Saavedra JM, Symes AJ. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2012; 37(13):2817-29. PubMed [journal]PMID: 22892395 PMCID: PMC3499714
PHA - Adjunct Faculty
Thomas E. Cote, Ph.D.
Name: Thomas E. Cote, Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Faculty Rank:
Associate Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Effects of Mu opiates on cell signaling
Email:
Office Phone:
(301) 295-3907
Department Website:
Bibliography
Biosketch Link:
Juliann G. Kiang, M.A., Ph.D.
Name: Juliann G. Kiang, M.A., Ph.D.
USU Department of Primary Appointment:
Pharmacology & Molecular Therapeutics
Title:
Adjunct Professor
Faculty Rank:
Professor
Location:
Uniformed Services University of the Health Sciences, Bethesda, MD
Research Interests:
Molecular mechanism underlying Radiation and drug development for radiation combined injury
Polytrauma Injury
Email:
Office Phone:
(301) 295-1076
Department Website:
Education
Postdoctoral, University of California, Berkeley, CA 1984-1988
Ph.D. University of California, Berkeley, CA, 1983
M.A. University of Nebraska, Omaha, NE, 1977
B.S. FuJen Catholic University, Taipei, Taiwan, ROC, 1975
Ph.D. University of California, Berkeley, CA, 1983
M.A. University of Nebraska, Omaha, NE, 1977
B.S. FuJen Catholic University, Taipei, Taiwan, ROC, 1975
Biography
Dr. Juliann Kiang is a principal investigator at Armed Forces Radiobiology Research Institute (AFRRI). She is Adjunct Professor in Department of Pharmacology and Molecular Therapeutics and in Department of Medicine, School of Medicine, Uniformed Services University of the Health Sciences (USU).
Dr. Kiang serves in editorial boards of several scientific journals, NIH and VA study sections, and USU committees. She worked in Water Reed Army Institute of Research from 1989 to 2006 before joining AFRRI.
Dr. Kiang is involved in studies showing corticotrophin-releasing factor and heat shock proteins are capable of protecting against edema/inflammation and hypoxia injury, respectively. She demonstrates that overexpression of inducible form of heat shock protein 70 kDa induced by sublethal heat stress, chemical stimulation, or the gene transfer produces thermotolerance and cross-tolerance that may be related to an inhibition of changes in intracellular calcium concentrations and expression of stress-related genes and proteins such as inducible nitric oxide synthase and p38-MAPK. She has found 17-DMAG, mesenchymal stem cells, G-CSF, ghrelin, or ciprofloxacin that can make cells endure much better under circumstances of low oxygen, a way to treat heat stroke, ischemia, hemorrhage, cancer, heart attack, stroke, or ionizing radiation injury.
Dr. Kiang had made four major contributions in her research career (journal references to work are noted).
Dr. Kiang is the first to demonstrate that treatment with corticotrophin-releasing factor (CRF) inhibits neurogenic and thermally-induced protein extravasation in rats (9-14). She also found that urotensin I and sauvagine (members of the CRF superfamily) possess the same properties as CRF but with greater potency (15). She holds a patent resulting from this work. She has provided evidence that CRF and its analogs increase intracellular Ca2+ concentrations in vitro (33, 36, 50), which are correlated with capacity of these neuropeptides to inhibit thermally-induced edema (50). CRF exerts its action on CRF type 2 receptors to activate enzymes such as tyrosine kinases, phospholipase 1 and 2 to lead to a result of increases in intracellular Ca2+ concentrations (56). A patent is resulted.
Dr. Kiang’s second major contribution is that she performed extensive research to establish the effect of heat shock on components of signal transduction pathways, such as H+, Ca2+, Na+, cAMP, inositol 1,4,5-trisphosphate, and heat shock proteins in cultured cells. Her findings in this area are wide-ranging and have extended knowledge in the heat shock field (18, 19, 22, 25, 29, 40-42, 44, 46-48, 51-55, 57, 58, 60-62). Her findings provide insight to unfold the mechanisms of tolerance and cross-tolerance (64, 67). Heat shock protein 70 kDa plays a very important role in cell survival – a fine-line before occurrence of apoptosis.
Dr. Kiang’s third major contribution is that she has shown heat shock protein 70 kDa (HSP-70i) can protect the rat ileum from the ischemia/reperfusion injury (37, 66), ricin injury (47), during ileitis (57), and the mouse jejunum, lung, heart, and kidney from the hemorrhagic shock (70). She has also shown that down-regulation of inducible nitric oxide synthase inhibits the activity of caspase-3, an apoptotic protease, and overexpression of HSP-70i prevents ATP loss resulted from hemorrhage (78, 87, 91, 99, 104) or radiation-injury (106-108, 110-114). The work has resulted in a provisional patent.
Dr. Kiang’s fourth major contribution is that she has characterized radiation combined injury (110, 111, 115, 120) shown that ciprofloxacin (122, 126-128, 134), ghrelin (130, 146), and bone marrow mesenchymal stem cells (132, 140) can combat radiation injury combined with skin-wound injury. The research work is ongoing. Meanwhile, she established a new combined injury model of radiation with hemorrhage (135, 138, 142, 145) that brought her the 2016 AFRRI Research Award.
Bubliography
Peer-reviewed publications (149)
1. Kiang JG, Dewey WL, and Wei ET. Tolerance to morphine bradycardia in the rat. J. Pharmacol Exp. Ther. 226:187 192, 1983.
2. Kiang JG and Wei ET. Inhibition of an opiate-induced vagal reflex in rats by naloxone, SMS 201 995 and ICI 154, 129. Regulatory Peptides 6:255 262, 1983.
3. Dashwood MR, Kiang JG, and Wei ET. An etorphine-evoked reflex in rats is inhibited by naloxone, N-methylnaloxone, and SMS 201 995. Arch. Int. Pharmacodyn. Ther. 266:77 82, 1983.
4. Kiang JG and Wei ET. Sensitivity to morphine-evoked bradycardia in rats is modified by dynorphin (1 13), (Leu)enkephalin and (Met)enkephalin. J. Pharmacol. Exp. Ther. 229:469 473, 1984.
5. Kiang JG and Wei ET. Peripheral opioid receptors influencing heart rate in rats: evidence for endogenous tolerance. Regulatory Peptides 8:297 303, 1984.
6. Tang J, Webber RJ, Chang D, Chang JK, Kiang JG, and Wei ET. Depressor and natriuretic activities of several atrial peptides. Regulatory Peptides 9:543 549, 1984.
7. Wei ET and Kiang JG. Peripheral opioid receptors influencing heart rate in rats. In: Opioid Peptides in the Periphery. (Eds, F. Fraioli, A. Isidori and M. Mazzetti) Developments in Neuroscience 18:95 101, 1984, Amsterdam, Elsevier.
8. Kiang JG and Wei ET. CRF-evoked bradycardia in urethane-anesthetized rats is blocked by naloxone. Peptides 6:409 413, 1985.
9. Kiang JG and Wei ET. CRF: an inhibitor of neurogenic plasma extravasation produced by saphenous nerve stimulation. Eur. J. Pharmacol. 114:111 112, 1985.
10. Wei ET, Kiang JG, Buchan P, and Smith T. Corticotropin-releasing factor (CRF) inhibits neurogenic plasma extravasation in the rat paw. J. Pharmacol. Exp. Ther. 238:783 787, 1986.
11. Kiang JG and Wei ET. Corticotropin-releasing factor (CRF) inhibits thermal injury. J. Pharmacol. Exp. Ther. 243:517- 520, 1987.
12. Wei ET and Kiang JG. Inhibition of protein exudation from the trachea by corticotropin-releasing factor. Eur. J. Pharmacol. 140:63-67, 1987.
13. Wei ET, Kiang JG, and Tien JQ. Anti-inflammatory activity of corticotropin-releasing factor: I. Efficacy studies. Proc. West. Pharmacol. Soc. 30:59 62, 1987.
14. Kiang JG, Poree L, and Wei ET. Anti-inflammatory activity of corticotropin-releasing factor: II. Mechanisms of action. Proc. West. Pharmacol. Soc. 30:63 65, 1987.
15. Wei ET and Kiang JG. Peptides of the corticoliberin superfamily attenuate thermal and neurogenic inflammation in rat paw skin. Eur. J. Pharmacol. 168:81 86, 1989.
16. Kiang JG and Colden-Stanfield M. Morphine induces an intracellular alkalinization in bovine aortic endothelial cells (BAECs), In: International Narcotic Research Conference (INRC) '89. (Eds. R. Quirion, K. Jhamandas and C. Gianoulakis) Alan Liss Press, N.Y., Prog. Clin. Biol. Res. 328:137 140, 1989.
17. Wei ET, Wong JC, and Kiang JG. Decreased inflammatory responsiveness of hypophysectomized rats to heat is reversed by a CRF antagonist. Regulatory Peptides 27:317 323, 1990.
18. Kiang JG, McKinney LC, and Gallin EK. Heat induces an intracellular acidification in human A 431 cells: role of Na+/H+ exchanger and metabolism. Am. J. Physiol., 259(Cell Physiol. 28):C727-C737, 1990.
19. Kiang JG, Wu YY, and Lin M. Hyperthermia elevates cAMP levels in human epidermoid A 431 cells. Biochem. J. 276:683 689, 1991.
20. Kiang JG. Effect of intracellular pH on cytosolic free [Ca2+]i in A-431 cells. Eur. J. Pharmacol. 207(Molecular Pharmacol. Section):287-296, 1991.
21. Lin W-W, Kiang JG, and Chuang D-M. Pharmacological characterization of endothelin-stimulated phosphoinositides breakdown and cytosolic Ca2+ rise in C6 rat glioma cells. J. Neurosci., 12:1077 1085, 1992.
22. Kiang JG, Koenig ML, and Smallridge RC. Heat shock increases cytosolic free Ca2+ concentration via the Na+/Ca2+ exchange in human epidermoid A 431 cells. Am. J. Physiol. 263(Cell Physiol. 32):C30-38, 1992.
23. Smallridge RC, Gist ID, and Kiang JG. Na+-H+ antiport and monensin effects on cytosolic pH and iodide transport in FRTL 5 rat thyroid cells. Am. J. Physiol. 262(Endocrinol. Metab.) 25:E834-E839, 1992.
24. Smallridge RC, Kiang JG, Gist ID, Fein HG, and Galloway R. U 72133 inhibits TRH-induced activities in GH3 cells. Endocrinol. 131:1883 1888, 1992.
25. Kiang JG and McClain DE. Effect of heat shock, Ca2+, and cAMP on inositol 1,4,5-trisphosphate in human epidermoid A 431 cells. Am. J. Physiol. 264 (Cell Physiol. 33):C1561-C1569, 1993.
26. Aloj SM, Liguoro D, Kiang JG, and Smallridge RC. Purinergic (P2) receptor -operated calcium entry into rat thyroid cells. Biophy. Biochim. Res. Comm. 195:1-7, 1993.
27. Kiang JG. Corticotropin-releasing factor increases cytosolic free calcium via receptor-mediated Ca2+ channels. Eur. J. Pharmacol. (Molecular Pharmacol. Section) 267:135-142, 1994.
28. Kiang JG and Smallridge RC. Sodium cyanide increases cytosolic free calcium: Evidence of activation of the reversed mode of Na+/Ca2+ exchanger and Ca2+ mobilization from inositol trisphosphate-insensitive pools. Toxicol. Appl. Pharmacol., 127:173-181, 1994.
29. Kiang JG, Carr FE, Burns MR, and McClain DE. HSP-72 synthesis is promoted by increase in [Ca2+]i or activation of G proteins but not pHi or cAMP. Am. J. Physiol. 267 (Cell Physiol. 36):C104-C114, 1994.
30. Tang T, Kiang JG, and Cox BM. Opioids acting through delta-receptors increase the intracellular free calcium concentration in the dorsal root ganglion neuroblastoma hybrid ND8-47 cells. J. Pharmacol. Exptl. Ther., 270:40-46, 1994.
31. Wang X, Kiang JG, and Smallridge RC. U-73122 inhibits increases in inositol trisphosphates and cytosolic free [Ca2+] induced by TSH in FRTL-5 cells. Bioph. Biochim. Acta, 1223:101-106, 1994.
32. Poola I and Kiang JG. The estrogen inducible transferrin receptor-like membrane glycoprotein is related to stress regulated proteins. J. Biol. Chem. 269:1-8, 1994.
33. Kiang JG, Wang XD, and McClain DE. Corticotropin-releasing factor increases protein kinase C activity by elevating isoforms and at the membrane. Chin J. Physiol. 37:105-110, 1994.
34. Wang XD, Kiang JG, and Smallridge RC. Identification of protein kinase C and its multiple isoforms in Frtl-5 thyroid cells. Thyroid 5:137-140, 1995.
35. Tang T, Kiang JG, Cote T, and Cox BM. Opioid-induced increase [Ca2+]i in ND8-47 neuroblastoma X DRG hybrid cells is mediated through G protein-coupled delta opioid receptors and desensitized by chronic exposure to opioid. J. Neurochem. 65:1612-1621, 1995.
36. Kiang JG. Mystixin-7 and Mystixin-11 increase [Ca2+]i and inositol trisphosphates in human A-431 cells. Eur. J. Pharmacol. (Mol. Pharmacol. Section) 291:107-113, 1995.
37. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Heat shock protein 72 kD induction protects rat intestinal mucosa from ischemia/reperfusion injury. Gastroenterol. 109:505-515, 1995.
38. Tang T, Kiang JG, Cote T, and Cox BM. Antisense oligodeoxynucleotide to Gái2 protein á-subunit sequence inhibits an opioid-induced increase in intracellular free calcium in ND8-47 neuroblastoma x DRG hybrid cells. Mol. Pharmacol. 48:189-193, 1995.
39. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Rapid assay of HSF1 and HSF2 gene expression by reverse transcriptase PCR. Mol. Cell Biochem. 158: 48-51, 1996.
40. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Increases in HSF1 translocation and synthesis in human epidermoid A-431 cells: role of protein kinase C and [Ca2+]i. J. Investig. Med. 44:144-153, 1996.
41. Kiang JG, Ding XZ, and McClain DE. Thermotolerance attenuates heat-induced increases in [Ca2+]i and HSP-72 synthesis but not heat-induced intracellular acidification in human A-431 cells. J. Investig. Med. 44:189-192, 1996.
42. Kiang JG, Wang XD, Ding XZ, Gist I, and Smallridge RC. Heat shock inhibits the hypoxia-induced effects on iodide uptake and signal transduction and enhances cell survival in rat thyroid FRTL-5 cells. Thyroid, 6:475-483, 1996.
43. Wang XD, Kiang JG, Atwa MA, and Smallridge RC. Evidence for the involvement of protein kinase C isoforms in á-1 adrenergic activation of phospholipase A2 in Frtl-5 thyroid cells, J. Investig. Med. 44:566-574, 1996.
44. Kiang JG and Koenig ML. Characterization of intracellular calcium pools in thermotolerant and their desensitization in thermotolerant cells. J. Investig. Med. 44:352-361, 1996.
45. Kiang JG and Tsokos GC. Signal transduction and heat shock protein expression. J. Biomed. Sci. 3:379-388, 1996.
46. Ding XZ, Tsokos GC, Smallridge RC, and Kiang JG. Heat shock gene expression in HSP-70 and HSF1 gene-transfected human epidermoid A-431 cells. Mol. Cell. Biochem. 167:145-152, 1997.
47. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Induction of the heat shock response limits tissue injury during acute inflammation of the rat ileum. Critical Care Medicine 25:309-317, 1997.
48. Ding XZ, Tsokos GC, and Kiang JG. Heat shock factor 1 protein in heat shock factor 1 gene-transfected human epidermoid A-431 cells requires phosphorylation prior to inducing heat shock protein-70 production. J. Clin. Investig. 99:136-143, 1997.
49. Liossis S-N, Ding XZ, Kiang JG, and Tsokos GC. Overexpression of HSP70 offers thermoprotection but enhances the TCR/CD3- and Fas-induced apoptotic death in Jurkat T-cells. J. Immunol. 158:5668-5675, 1997.
50. Kiang JG. Corticotropin-releasing factor-like peptides increase cytosolic free calcium in human epidermoid A-431 cells. Eur. J. Pharmacol. (Molecular Pharmacology Section), 329:237-244, 1997.
51. Kiang JG, Gist ID, and Tsokos GC. 17-Estradiol-induced increases in glucose-regulated proteins protect human breast cancer T47-D cells from thermal injury. Chin. J. Physiol. 40:213-219, 1997.
52. Kiang JG, Ding XZ, and McClain DE. Overexpression of HSP-70 attenuates increases in [Ca2+]i and protects human epidermoid A-431 cells after chemical hypoxia. Toxicol. Appl. Pharmacol. 149:185-194, 1998.
53. Ding XZ, Tsokos GC, and Kiang JG. Overexpression of HSP-70 inhibits the phosphorylation of HSF1 by activating protein phosphatase and inhibiting protein kinase C activity. FASEB. J. 12:451-459, 1998.
54. Kiang JG, Gist ID, and Tsokos GC. Cytoprotection and regulation of heat shock proteins induced by heat shock in human breast cancer T47-D cells: role of [Ca2+]i and protein kinases. FASEB J. 12: 1571-1579, 1998.
55. Kiang JG and Tsokos GC. Heat shock protein 70 kD family: Molecular Biology, Biochemistry, and Physiology. Pharmacol.Ther. 80:183-201, 1998.
56. Kiang JG, Ding XZ, Gist ID, and Tsokos GC. Corticotropin-releasing factor increases phosphotyrosine of phospholipase C- at tyrosine residues via its receptor 2 in human epidermoid A-431 cells. Eur. J. Pharmacol. 363:203-210, 1998.
57. Goldhill JM, Stojadinovic A, KiangJG, Smallridge RC, and Shea-Donohue T. Hyperthermia prevents functional, histological and biochemical abnormalities induced during ileitis. Neurogastroenterol. Mot. 11:69-76, 1999.
58. Kiang JG, Gist ID, and Tsokos GC. Biochemical requirement of heat shock protein 72 kD expression in human breast cancer MCF-7 cells. Mol. Cell. Biochem.199: 179-188, 1999.
59. Wang XD, Kiang JG, Scheibel LW, and Smallridge RC. Phospholipase C activation by Na+/Ca2+ exchange is essential for monensin-induced Ca2+ influx and arachidonic release in FRTL-5 thyroid cells. J. Investig. Med., 47:388-396, 1999.
60. Kiang JG and McClain DE. N-nitro-L-arginine decreases resting cytosolic [Ca2+] and enhances heat stress-induced increase in cytosolic [Ca2+] in human colon carcinoma T84 cells. Chin. J. Physiol. 42: 153-160, 1999.
61. Smallridge RC, Gist ID, Tsokos GC, and Kiang JG. Characterization of distinct heat shock and thapsigargin-induced cytoprotective proteins in FRTL-5 cells. Thyroid, 9: 1041-1047, 1999.
62. Kiang JG, Gist ID, and Tsokos GC. Heat shock induces expression of heat shock protein 72 kD and 90 kD in human breast cancer MDA-231 cells. Mol. Cell. Biochem. 204: 169-178, 2000.
63. Kiang JC and Lu PY. Biological effects of qigong and an overview of research design and methodology. Proceedings: The Science and Spirituality of Healing, 1: 99-121, 2000.
64. Kiang JG, Kiang SC, Juang Y-T, and Tsokos GC. Nω-nitro-L-arginine inhibits the inducible heat shock protein 70 kDa via Ca2+, PKC, and PKA. Am. J. Physiol. 282:G415-G423, 2002.
65. Kiang JG, Marotta D, Wirkus M, Wirkus M, and Jonas WB. External bioenergy increases intracellular free calcium concentrations and reduces cellular response to heat stress. J. Investig. Med., 50: 38-45, 2002.
66. Fleming SD, Starnes BW, Kiang JG, Stojadinovic A, Tsokos GC, and Shea-Donohue T. Heat stress protection against mesenteric ischemia/reperfusion-induced alteration in intestinal mucosa in rats. J. Appl. Physiol. 92:2600-2607, 2002.
67. Kiang JG. Genistein inhibits herbimycin A-induced inducible heat shock protein 70 kDa. Mol Cell Biochem, 245:191-199, 2003.
68. Kiang JG, McClain DE, Warke VG, Krishnan S, and Tsokos GC. Constitutive NO synthase regulates the Na+/Ca2+ exchanger in human Jurkat T cells: role of [Ca2+]i and tyrosine phosphorylation. J. Cellular Biochem., 89:1030-1043, 2003.
69. Kiang JG, Warke VG, and Tsokos GC. NaCN-induced chemical hypoxia is associated with altered gene expression. Mol Cell Biochem 254:211-216, 2003.
70. Kiang JG, Bowman DP, Wu BW, Hampton N, Kiang AG, Zhao B, Juang Y-T, Atkins JL, and Tsokos GC. Geldanmaycin inhibits hemorrhage-induced increases in caspase-3 activity, KLF6, and iNOS expression in unresuscitated organs of mice: Role of inducible HSP-70. J Appl Phsiol 97:564-569, 2004.
71. Kiang JG, Bowman PD, Zhao B, Atkins JL, and Tsokos GC. Heat shock protein-70 inducers and iNOS inhibitors as therapeutics to ameliorate hemorrhagic shock. NATO-HFM-109-P28:1-11, 2004.
72. Fleming SD, Kiang JG, and Tsokos GC. Targeting complement in treatment of ischemia/reperfusion-induced injury. NATO-HFM-109-P24:1-13, 2004.
73. Bowman PD, Zhao B, Bynum JA, Sondeen JL, Kiang JG, Dubick MA, and Atkins JL. Application of gene expression analysis with microarrays and proteinomics to the problem of hemorrhagic shock and resuscitation. NATO-HFM-109-P29:1-15, 2004.
74. Kiang JG. Inducible heat shock protein 70 kD and inducible nitric oxide synthase in hemorrhage/resuscitation-induced injury. Cell Res 14:450-459, 2004.
75. Kiang JG, Ives JH, and Jonas WB. External bioenergy-induced increases in intracellular free calcium concentrations are mediated by the Na+/Ca2+ exchanger and L-type calcium channel. Mol Cell Biochem 271:51-59, 2005.
76. Kiang JG. Lu X, Tabaku LS, Bentley TB, Atkins JL, and Tsokos GC. Resuscitation with lactated Ringers solution limits the expression of molecular events associated with lung injury after hemorrhage. J Appl Physiol 98:550-556, 2005.
77. Krishnan S, Kiang JG, Fisher CU, Nambiar MP, Nguyen HT, Kyttaris VC, Chowdhury B, Rus V, Tsokos GC. Increased caspase-3 expression and activity contributes to reduced CD3 expression in Systemic Lupus Erythematosus T cells. J Immunol 175:3417-3423, 2005.
78. Kiang JG, Bowman DP, Lu X, Li Yansong, Ding XZ, Zhao B, Juang YT, Atkins JL, Tsokos GC. Geldanmaycin treatment prevents hemorrhage-induced ATP loss in mouse organs by overexpressing HSP-70 and activating pyruvate dehydrogenase. Am J Physiol 291:G117-G127, 2006.
79. Tsen KT, Tsen SWD, Kiang JG. Lycopene is more potent than bata carotene in the neutralization of singlet oxygen: role of energy transfer probed by ultrafast Raman spectroscopy. J Biomed Optics 11:064025 (6 pages), 2006.
80. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN: Dependence on the injected carrier density. App Physics Lett 89:11211 (3 pages), 2006.
81. Tsen KT, Kiang JG, Ferry DK, Kochelap VA, Komirenko SM, Kim KW, Morkoc H. Subpicosecond Raman studies of electric-field-induced optical phonon instability in an In0.53Ga0.47As-based semiconductor nanostructure. J Phys: Condens Matter 18:7961-7974, 2006.
82. Kiang JG, Tsen KT. Biology of hypoxia. Chin J Physiol 49:223-233, 2006.
83. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Observation of the low frequency vibrational modes of bacteriophage M13 in water by Raman spectroscopy. Virology J 3:79 (11 pages), 2006.
84. Tsen KT, Dykeman E, Sankey OF, Lin N-T, Tsen S-WD, Kiang JG. Raman scattering studies of the low frequency vibrational modes of bacteriophage M13 in water. Nanotecnology 17:5474-5479, 2006.
85. Tsen KT, Kiang JG, Ferry DK, and Morkoc H. Subpicosecond time-resolved Raman studies of field-induced transient transport in an -based p-i-n semiconductor nanostructure. App Physics Lett, 89: 262101 (3 pages), 2006.
86. Tsen KT, Kiang JG, and Ferry DK. Subpicosecond transient Raman scattering studies of field-induced electron transport in an -based p-i-n nanostructure: Direct observation of the effects of electron momentum randomization. J Phys: Condens Matter 18:L585-L592, 2006.
87. Kiang JG, Peckham RM, Duke LE, Chaudry IH, Tsokos GC. Androstenediol inhibits trauma-hemorrhage-induced increase in caspase-3 by downregulating inducible nitric oxide synthase pathway. J App Physiol 102: 933-941, 2007.
88. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Probing the low frequency vibrational modes of viruses with Raman scattering -- bacteriophage M13 in water. J Biomed Optics. 12: 024009 (6 pages), 2007.
89. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN. Proc of SPIE 6473: 64730Q-1 – 64730Q-12, 2007.
90. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Studies of longitudinal optical phonons in GaN by sybpicosecond time-resolved Raman Spectroscopy. Proc of SPIE 6471: 64710X-1 – 64710X-10, 2007.
91. Kiang JG, Bowman DP, Lu X, Li Y, Wu BW, Loh HH, Tsen KT, Tsokos GC. Geldanmaycin treatment inhibits hemorrhage-induced increases in caspase-3 activity: Role of inducible nitric oxide synthase. J App Physiol 103: 1045-1055, 2007.
92. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Direct measurements of the lifetimes of longitudinal optical phonon modes and their dynamics in InN. App Physics Lett 90: 152107 (3 pages), 2007.
93. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Subpicosecond time-resolved Raman studies of electron-longitudinal optical phonon interactions in InN. App Physics Lett 90: 172108 (3 pages), 2007.
94. Tsen KT, Kiang JG, Ferry DK, Lu H, Schaff WJ, Lin HW, Gwo S. Electron-density dependence of longitudinal-optical phonon lifetime in InN studied by subpicosecond time-resolved Raman spectroscopy. J Phy Condens Matter 19: 236219 (8 pages), 2007.
95. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by coherent excitations with low power visible femtosecond laser. Virology J 4:50 (6 pages), 2007.
96. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses with a very low power visible femtosecond laser. J Physics: Condens Matter 19:322102 (9 pages), 2007.
97. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by laser-driven coherent excitations via impulsive stimulated Raman scattering process. J Biomed Optics 12:064030 (6 pages), 2007.
98. Tsen KT, TsenS-W D, Sankey OF, Kiang JG. Selective inactivation of microorganisms by near-IR femosecond laser pulses. J Phy Condens Matter 19: 472201 (7 pages), 2007.
99. Kiang JG, Krishnan S, Lu X, Li Y. Inhibition of inducible nitric oxide synthase protects human T cells from hypoxia-induced injury. Mol Pharmacol 73:738-747, 2008.
100. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kiang JG. Selective inactivation of human immunodeficiency virus with subpicosecond near-infrared laser pulses. J Phys Condens matter 20:25220 (4 pages), 2008.
101. Atkins JL, Hammamiech R, Jett M, Gorbounov NV, Asher LV, Kiang JG. α-Defensin-4 and asymmetric dimethyl arginine (ADMA) increase in mesenteric lymph after hemorrhage in anesthetized rats. Shock 30: 411-146, 2008.
102. Tsen KT, Tsen S-W D, Chang C-L, Hung C-F, Wu T-C, Ramakrishna K, Mossman K, Kiang JG. Inactivation of viruses with a femtosecond laser via impulsive stimulated Raman scattering. In: Optical Interactions with Tissue and Cells XIX (edited by Steven L. Jacques, William P. Roach, Robert J. Thomas), Proc. of SPIE 6854: 68540N1-6854N10, 2008.
103. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Dynamics of LO phonons in InN studied by subpicosecond time-resolved Raman spectroscopy. In: Ultrafast Phenomena in Semiconductors and Nanostructure Materials XII (edited by J.J. Song, K.T. Tsen, M. Betz and A. Elezzabi), Proc. of SPIE Vol. 6892: 689206 (12 pages), 2008.
104. Kiang JG, Kiang SC, Bowman PD. 17-DMAG inhibits hemorrhage-induced injury in small intestine and lung by inactivating caspase-3. International Proceedings of International Shock Congress K628C0171:23-27, 2008.
105. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kibler K, Jacob B, Kiang JG. Selective inactivation of human immunodeficiency virus with an ultrashort pulsed laser. Proc. of SPIE 7175: 717510-1 – 717510-8, 2009.
106. Kiang JG, Smith JA, and Agravante NG. Geldanamycin analog 17-DMAG inhibits iNOS and caspases in gamma irradiated human T cells. Radiat Res 172: 321-330, 2009.
107. Gorbunov NV, Kiang JG. Up-regulation of Autophagy in the Small Intestine Paneth Cell in Response to Total-Body γ-Irradiation. J Pathol 219: 242-252, 2009.
108. Jiao W, Kiang JG, Cary L, Elliott TB, Pellmar TC, Ledney GD. COX-2 inhibitors are contraindicated for therapy of combined injury. Radiat Res 172: 686-697, 2009.
109. Tsen KT, Tsen S-WD, Fu Q, Lindsay SM, Kibler K, Jacobs B, Wu TC, Karanam B, Jagu S, Roden RBS, Hung C-F, Sankey OF, Ramakrishna B, Kiang JG. Photonic approach to the selective inactivation of viruses with a near-infrared subpicosecond fiber laser. J Biomed Opt 14: 064042 (10 pages), 2009.
110. Kiang JG, Jiao W, Cary L, Mog SR, Elliott TB, Pellmar TC, Ledney GD. Wound trauma increases radiation-induced mortality by increasing iNOS, cytokine concentrations, and bacterial infections. Radiate Res 173: 319-332, 2010.
111. Kiang JG, Garrison BR, Gorbunov NV. Radiation combined injury: DNA damage, apoptosis, and autophagy. Adapt Med 2: 1-10, 2010. doi: 10.4247/AM.2010.ABA004.
112. Daly MJ, Gaidamakova EK, Matrosova VY, Kiang JG, Fukumoto R, Wehr NB, Viteri G, Berlett BS, Levine RL. Small molecule proteome-shield in Deinococcus radiodurans. PLoS One 5(9): e12570 (15 pages), 2010.
113. Gorbunov NV and Kiang JG. Activation of IL-1β pathway and augmentation of Paneth cell α-defensin-4 in small intestine following total-body γ-irradiation. Intl J Immunopathol Pharmacol 23: 1111-1123, 2010.
114. Kiang JG, Smith JA, Agravante NG, Gorbunov NV. Geldanamycin analog 17-DMAG has radioprotective activity in mice. Radiat Res, in review.
115. Fukumoto R, Kiang JG. Geldanamycin analog 17-DMAG limits apoptosis in human peripheral blood cells by inhibition of p53 activation and its interaction with heat shock protein 90 kDa after ionizing radiation. Radiat Res 176: 333-345, 2011.
116. Kiang JG, Agravante NG, Smith JT, Bowman PD. 17-DMAG increases Bcl-2 and inhibits hemorrhage-induced increases in iNOS activation, caspase-3 activity and TNF-a. Cell & Bioscience 1: 21 (10 pages), 2011.
117. Tsen KT, Tsen SWD, Fu Q, Lindsay SM, Li Z, Yan H, Cope S, Vaiana S, Kiang JG. Studies of inactivation of encephalomyocaditis virus, M13 bacteriophage and Salmomella typhimurium by using a visible femtosecond laser irradiation: insight into the possible inactivation mechanisms. J Biomed Optics 16: 078003 (11 pages), 2011.
118. Whitnall MH, Cary LH, Moroni M, Ngudiankama BF, Landauer MR, Singh VK, Ghosh SP, Kulkarni S, Miller AC, Kiang JG, Srinivasan V, Xiao M. United States Armed Forces Radiobiology Research Institute countermeasures program and related policy questions. Proceedings,Hiroshima University, 2012.
119. Kiang JG, Garrison BR, Burns TM, Zhai M, Dews IC, Ney PH, Fukumoto R, Cary LH, Elliott TB, Ledney GD. Wound trauma alters ionizing radiation dose assessment. Cell Bioscience 2: 20 (12 pages), 2012.
120. Tsen S-W D, Wu TC, Kiang JG, Tsen KT. Prospects for a novel ultrashort pulsed laser technology for pathogen inactivation. J Biomed Sci 19: 62 (11 pages), 2012.
121. Kiang JG. Overview of biological effects of irradiation combined injury. NATO-HFM-223-P5:1-18, 2012.
122. Fukumoto R, Cary LH, Gorbunov NV, Elliott TB, Kiang JG. Ciprofloxacin modulates cytokine profiles, accelerates bone marrow recovery and mitigates ileum injury after radiation combined with wound trauma. PLoS One 8: e58389 (11 pages), 2013. doi: 10.1371/journal.pone.0058389. PMID: 23520506
123. Gorbunov NV, Garrison BR, McDaniel DP, Zhai M, Liao1 P-J, Nurmemet N, Kiang JG. Adaptive redox response of mesenchymal stromal cells to stimulation with lipopolysaccharide inflammagen: mechanisms of remodeling of tissue barriers in sepsis. Oxid Med Cell Longev 2013: 186795 (16 pages), 2013. doi: 10.1155/2013/186795. PMID: 23710283
124. Lu X, Nurmemet D, Bolduc DL, Elliott TB, Kiang JG. Radioprotective effects of oral 17-DMAG in mice: Bone marrow and small intestine. Cell Bioscience 3: 36 (16 pages), 2013. doi: 10.1186/2045-3701-3-36. PMID: 24499553
125. Kiang JG, Ledney GD. Skin injuries reduce survival and modulate corticosterone, C-reactive protein, complement component 3, IgM, and prostaglandin E2 after whole-body reactor-produced mixed field (n + γ-photons) irradiation. Oxid Med Cell Longev, 2013: 821541 (10 pages), 2013. doi: 10.1155/2013/821541. PMID: 24175013
126. Kiang JG, Garrison BR, Smith JT, Fukumoto R. Ciprofloxacin as a potential radio-sensitizer to tumor cells and a radioprotectant for normal cells: Differential effects on -H2AX formation, p53 phosphorylation, Bcl-2 production, and cell death. Cell Mol Biochem 393: 133-143, 2014. doi: 10.1007/s11010-014-2053-z. PMID: 24802382
127. Kiang JG, Fukumoto R. Ciprofloxacin increases survival after ionizing irradiation combined injury: gamma-H2AX formation, cytokine/chemokine, and red blood cells. Health Physics 106: 720-726, 2014. doi: 10.1097/HP.0000000000000108. PMID: 24776905
128. Fukumoto R, Burns TM, Kiang JG. Ciprofloxacin Enhances Stress Erythropoiesis in Spleen and Increases Survival after Whole-Body Irradiation Combined with Skin-Wound Trauma, PLoS One 9(2): e90448, 2014. doi: 10.1371/journal.pone.0090448. PMID: 24587369
129. Kiang JG, Zhai M, Liao P-J, Bolduc DL, Elliott TB, Gorbunov NV. Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn. Oxid Med Cell Longev 2014: 481392 (10 pages), 2014. doi: 10.1155/2014/481392. PMID: 24738019
130. Kiang JG, Zhai M, Liao P-J, Elliott TB, Gorbunov NV. Ghrelin therapy improves survival after whole-body ionizing irradiation combined with wound or burn: Amelioration of leukocytopenia, thrombopenia, splenomegaly, and bone marrow injury. Oxid Med Cell Longev 2014: 215858, 2014. doi: 10.1155/2014/215858. PMID: 25374650
131. Gorbunov NV, Elliott TB, McDaniel DP, Zhai M, Liao P-J, Kiang JG. Mitophagy and mitochondrial remodeling in mouse mesenchymal stromal cells following a challenge with Staphylococcus epidermidis. J Cell Mol Med 19:1133-1150, 2015. doi: 10.1111/jcmm.12518. PMID: 25721260
132. Kiang JG, Gorbunov NV. Bone marrow mesenchymal stem cells increases survival after ionizing irradiation combined with wound trauma: Characterization and therapy. J Cell Sci Ther 5:190 (8 pages), 2014. doi: 10.4172/2157-7013.1000190
133. Elliott TB, Bolduc DL, Ledney GD, Kiang JG, Fatanmi OO, Wise S, Romaine PLP, Newman VL, Singh VK. Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in mice exposed to radiation and combined injury. Int J Radiat Biol 91(9):690-702, 2015. doi: 10.3109/09553002.2015.1054526. PMID: 25994812
134. Swift JM, Smith JT, Kiang JG. Ciprofloxacin therapy mitigates ATP loss after irradiation combined with wound trauma: Preservation of pyruvate dehydrogenase and inhibition of pyruvate dehydrogenase kinase 1. Radiat Res 183: 684-692, 2015. PMID: 26010714
135. Swift JM, Smith JT, Kiang JG. Hemorrhage Trauma Increases Radiation-Induced Trabecular
Bone Loss and Marrow Cell Depletion in Mice. Radiat Res 183: 578-583, 2015. doi: 10.1667/RR13960.1 PMID: 25897554
136. Swift JM, Swift SN, Smith JT, Kiang JG, Allen MR. Skin wound trauma, following high-dose radiation exposure, amplifies and prolongs skeletal tissue loss. Bone 81: 487-494, 2015. doi: 10.1016/j.bone.2015.08.022 PMID: 26335157
137. Islam A, Bolduc DL, Zhai M, Kiang JG, Swift JM. Daily Captopril Dosing Increases Survival after Whole-Body Ionizing Irradiation but Decreases Survival after in combination with Combined Burn Trauma in Mice. Radiat Res 184:273-279, 2015. doi: 10.1667/RR14113.1. PMID: 26305295
138. Kiang JG, Smith JT, Anderson MN, Swift JM, Gupta P, Balakathiresan N, Maheshwari RK. Hemorrhage exacerbates radiation effects on survival, leukocytopenia, thrombopenia, erythropenia, bone marrow cell depletion and hematopoiesis, and inflammation-associated microRNAs expression in kidney. PLoS ONE 10:e0139271, 2015. doi: 10.1371/journal.pone.0139271. PMID: 26422254
139. Klionsky DJ…Kiang JG…Zughaler SM. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12: 1-222, 2016. PMID: 26799652
140. Kiang JG. Adult mesenchymal stem cells and radiation injury. Health Phys 111:198-203, 2016. doi: 10.1097/HP.0000000000000459. PMID: 27356065
141. Gupta P, Gayen M, Smith JT, Matrosova VY, Gaidamakova EK, Daly MJ, Kiang JG, Maheshwari RK. MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation. PLoS One 11: e0160575, 2016. doi: 10.1371/journal.pone.0160575. PMID: 27500529
142. Kiang JG. Exacerbation of mild hypoxia on acute radiation syndrome and subsequent mortality. Adaptive Med 9(1): 28-33, 2017. doi: 10.4247/AM.2017.ABG170
143. Kiang JG, Zhai M, Liao P.-J., Ho C, Gorbunov NV, Elliott TB. Thrombopoietin receptor agonist mitigate hematopoietic acute radiation syndrome and improves survival after whole-body ionizing irradiation followed by wound trauma. Mediators of Inflammation 2017:7582079, 2017. doi: 10.1155/2017/7582079 PMID: 28408792
144. Kiang JG, Zhai M, Bolduc DL, Smith JT, Anderson MN, Ho C, Lin B, Jiang S. Combined therapy of pegylated-G-CSF and Alx4100TPO improves survival and mitigate acute radiation syndrome after whole-body ionizing irradiation alone and followed by wound trauma. Radiat Res 188:476-490, 2017. doi: 10.1667/RR14647.1 PMID: 28850300
145. Kiang JG, Smith JT, Anderson MN, Elliott TB, Gupta P, Balakathiresan N, Maheshwari RK, Knollmann-Ritschel B. Hemorrhage enhances cytokine, complement component 3, and caspase-3, and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury. PLoS ONE 12(9):e0184393, 2017. doi: 10.1371/journal.pone.0184393.PMID: 28934227
146. Gorbunov NV, Kiang JG. Ghrelin therapy decreases incidents of intracranial hemorrhage in mice after whole-body ionizing irradiation combined with burn trauma. Int J Mol Sci 18(8). pii: E1693, 2017. doi: 10.3390/ijms18081693. PMID: 28771181
147. Kiang JG, Smith JT, Hegge SR, Ossetrova N. Circulating cytokine/chemokine concentrations respond to ionizing radiation doses but not radiation dose rates: granulocyte-colony stimulating factor and interleukin-18. Radiat Res, in press, 2018.
148. Kiang JG, Anderson MN, Smith JT. Ghrelin therapy sustains granulocyte colony-stimulating factor and keratinocyte factor to mitigate hematopoietic syndrome and spleen after whole-body ionizing irradiation combined with wound. Cell Biosci 8:27, 2018. doi: 10.1186/s13578-018-0225-3.
149. Li X, Cui W, Hull L, Smith JT, Kiang JG, Xiao M. Effects of low-moderate doses of γ-radiation on mouse hematopoietic and immune system. Radiat Res, in review, 2018.
E-Book (1)
1. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. Cell Biology Research Progress, Nova Science Publishers, INC. Hauppauge, NY. ISBN: 978-1-62417-374-5 http://www.novapublishers.com, 2012.
Book chapters (10)
1. Yan X, Lu PY, and Kiang JG. Qigong: basic science studies in Biology. In: Healing, Intention, and Energy medicine Science, Research Methods and Clinical Implications. (Eds. WB Jonas and C Crawford) Churchill Livingstone, London, UK pp. 103-119, 2003.
2. Kiang JG and McClain DE. Heat stress. In: Combat Medicine Basic and Clinical Research in Military, Trauma, and Emergency Medicine (Eds. GC Tsokos and JL Atkins), Humana Press, New Jersey, pp. 83-101, 2003.
3. Kiang JG. Human bioenergy effects at the cellular and molecular level. In: Life and Mind In Search of Physical Basis (ed. S. Savva), Trafford Publishing, Victoria BC, Canada, pp. 117-137, 2007.
4. Tsen KT, Tsen SWD, Dykeman EC, Sankey OF, Kiang JG. Inactivation of viruses with femtosecond laser pulses. In: Contemporary Trends in Bacteriophage research (Ed: Horace T. Adams), Nova Science Publishers, NY, ISBN: 978-1-60692-181-4, pp. 151-177, 2009.
5. Kumar KS, Kiang JG, Whitnall MH, Hauer-Jensen M. Perspectives in radiological and nuclear countermeasures. In: Textbook of Military Medicine, pages 239-266, 2012.
6. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. In: Autophagy: Principles, Regulation and Roles in Disease (ed: Gorbunov NV), Nova Science Pulbishers, INC. Hauppauge, NY. 2012.
7. Gorbunov NV, Garrison BR, Zhai M, McDaniel DP, Ledney GD, Elliott TB, Kiang JG. Autophagy-mediated defense response of mouse mesenchymal stromal cells (MSCs) to challenge with Escherichia coli. In: Protein Interaction / Book 1; ISBN 979-953-307-577-7. Eds.: Cai J and Wang H. InTech Open Access Publisher; www.intechweb.org. pp. 23-44, 2012.
8. Kiang JG, Fukumoto R, Gorbunov NV. Lipid peroxidation after ionizing irradiation leads to apoptosis and autophagy. In: Lipid Peroxidation; ISBN 980-953-307-143-0. Eds.: Angel Catala, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp.261-278, 2012.
9. Gorbunov NV, Elliott TB, McDaniel DP, Lund K, Liao PJ, Zhai M, Kiang JG. Up-regulation of autophagy defense mechanisms in mouse mesenchymal stromal cells in response to ionizing irradiation followed by bacterial challenge. In: Autophagy, ISBN 980-953-307-971-9. Ed: Yannick Bailly, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp. 331-350, 2013.
10. Kiang JG. Characterization and therapeutic uses of adult mesenchymal stem cells. In: Stem Cell Toxicity and Medicine (ed. S.C. Sahu). Wiley & Sons, West Sussex, pp. 288-301, 2016.
Dr. Kiang serves in editorial boards of several scientific journals, NIH and VA study sections, and USU committees. She worked in Water Reed Army Institute of Research from 1989 to 2006 before joining AFRRI.
Dr. Kiang is involved in studies showing corticotrophin-releasing factor and heat shock proteins are capable of protecting against edema/inflammation and hypoxia injury, respectively. She demonstrates that overexpression of inducible form of heat shock protein 70 kDa induced by sublethal heat stress, chemical stimulation, or the gene transfer produces thermotolerance and cross-tolerance that may be related to an inhibition of changes in intracellular calcium concentrations and expression of stress-related genes and proteins such as inducible nitric oxide synthase and p38-MAPK. She has found 17-DMAG, mesenchymal stem cells, G-CSF, ghrelin, or ciprofloxacin that can make cells endure much better under circumstances of low oxygen, a way to treat heat stroke, ischemia, hemorrhage, cancer, heart attack, stroke, or ionizing radiation injury.
Dr. Kiang had made four major contributions in her research career (journal references to work are noted).
Dr. Kiang is the first to demonstrate that treatment with corticotrophin-releasing factor (CRF) inhibits neurogenic and thermally-induced protein extravasation in rats (9-14). She also found that urotensin I and sauvagine (members of the CRF superfamily) possess the same properties as CRF but with greater potency (15). She holds a patent resulting from this work. She has provided evidence that CRF and its analogs increase intracellular Ca2+ concentrations in vitro (33, 36, 50), which are correlated with capacity of these neuropeptides to inhibit thermally-induced edema (50). CRF exerts its action on CRF type 2 receptors to activate enzymes such as tyrosine kinases, phospholipase 1 and 2 to lead to a result of increases in intracellular Ca2+ concentrations (56). A patent is resulted.
Dr. Kiang’s second major contribution is that she performed extensive research to establish the effect of heat shock on components of signal transduction pathways, such as H+, Ca2+, Na+, cAMP, inositol 1,4,5-trisphosphate, and heat shock proteins in cultured cells. Her findings in this area are wide-ranging and have extended knowledge in the heat shock field (18, 19, 22, 25, 29, 40-42, 44, 46-48, 51-55, 57, 58, 60-62). Her findings provide insight to unfold the mechanisms of tolerance and cross-tolerance (64, 67). Heat shock protein 70 kDa plays a very important role in cell survival – a fine-line before occurrence of apoptosis.
Dr. Kiang’s third major contribution is that she has shown heat shock protein 70 kDa (HSP-70i) can protect the rat ileum from the ischemia/reperfusion injury (37, 66), ricin injury (47), during ileitis (57), and the mouse jejunum, lung, heart, and kidney from the hemorrhagic shock (70). She has also shown that down-regulation of inducible nitric oxide synthase inhibits the activity of caspase-3, an apoptotic protease, and overexpression of HSP-70i prevents ATP loss resulted from hemorrhage (78, 87, 91, 99, 104) or radiation-injury (106-108, 110-114). The work has resulted in a provisional patent.
Dr. Kiang’s fourth major contribution is that she has characterized radiation combined injury (110, 111, 115, 120) shown that ciprofloxacin (122, 126-128, 134), ghrelin (130, 146), and bone marrow mesenchymal stem cells (132, 140) can combat radiation injury combined with skin-wound injury. The research work is ongoing. Meanwhile, she established a new combined injury model of radiation with hemorrhage (135, 138, 142, 145) that brought her the 2016 AFRRI Research Award.
Bubliography
Peer-reviewed publications (149)
1. Kiang JG, Dewey WL, and Wei ET. Tolerance to morphine bradycardia in the rat. J. Pharmacol Exp. Ther. 226:187 192, 1983.
2. Kiang JG and Wei ET. Inhibition of an opiate-induced vagal reflex in rats by naloxone, SMS 201 995 and ICI 154, 129. Regulatory Peptides 6:255 262, 1983.
3. Dashwood MR, Kiang JG, and Wei ET. An etorphine-evoked reflex in rats is inhibited by naloxone, N-methylnaloxone, and SMS 201 995. Arch. Int. Pharmacodyn. Ther. 266:77 82, 1983.
4. Kiang JG and Wei ET. Sensitivity to morphine-evoked bradycardia in rats is modified by dynorphin (1 13), (Leu)enkephalin and (Met)enkephalin. J. Pharmacol. Exp. Ther. 229:469 473, 1984.
5. Kiang JG and Wei ET. Peripheral opioid receptors influencing heart rate in rats: evidence for endogenous tolerance. Regulatory Peptides 8:297 303, 1984.
6. Tang J, Webber RJ, Chang D, Chang JK, Kiang JG, and Wei ET. Depressor and natriuretic activities of several atrial peptides. Regulatory Peptides 9:543 549, 1984.
7. Wei ET and Kiang JG. Peripheral opioid receptors influencing heart rate in rats. In: Opioid Peptides in the Periphery. (Eds, F. Fraioli, A. Isidori and M. Mazzetti) Developments in Neuroscience 18:95 101, 1984, Amsterdam, Elsevier.
8. Kiang JG and Wei ET. CRF-evoked bradycardia in urethane-anesthetized rats is blocked by naloxone. Peptides 6:409 413, 1985.
9. Kiang JG and Wei ET. CRF: an inhibitor of neurogenic plasma extravasation produced by saphenous nerve stimulation. Eur. J. Pharmacol. 114:111 112, 1985.
10. Wei ET, Kiang JG, Buchan P, and Smith T. Corticotropin-releasing factor (CRF) inhibits neurogenic plasma extravasation in the rat paw. J. Pharmacol. Exp. Ther. 238:783 787, 1986.
11. Kiang JG and Wei ET. Corticotropin-releasing factor (CRF) inhibits thermal injury. J. Pharmacol. Exp. Ther. 243:517- 520, 1987.
12. Wei ET and Kiang JG. Inhibition of protein exudation from the trachea by corticotropin-releasing factor. Eur. J. Pharmacol. 140:63-67, 1987.
13. Wei ET, Kiang JG, and Tien JQ. Anti-inflammatory activity of corticotropin-releasing factor: I. Efficacy studies. Proc. West. Pharmacol. Soc. 30:59 62, 1987.
14. Kiang JG, Poree L, and Wei ET. Anti-inflammatory activity of corticotropin-releasing factor: II. Mechanisms of action. Proc. West. Pharmacol. Soc. 30:63 65, 1987.
15. Wei ET and Kiang JG. Peptides of the corticoliberin superfamily attenuate thermal and neurogenic inflammation in rat paw skin. Eur. J. Pharmacol. 168:81 86, 1989.
16. Kiang JG and Colden-Stanfield M. Morphine induces an intracellular alkalinization in bovine aortic endothelial cells (BAECs), In: International Narcotic Research Conference (INRC) '89. (Eds. R. Quirion, K. Jhamandas and C. Gianoulakis) Alan Liss Press, N.Y., Prog. Clin. Biol. Res. 328:137 140, 1989.
17. Wei ET, Wong JC, and Kiang JG. Decreased inflammatory responsiveness of hypophysectomized rats to heat is reversed by a CRF antagonist. Regulatory Peptides 27:317 323, 1990.
18. Kiang JG, McKinney LC, and Gallin EK. Heat induces an intracellular acidification in human A 431 cells: role of Na+/H+ exchanger and metabolism. Am. J. Physiol., 259(Cell Physiol. 28):C727-C737, 1990.
19. Kiang JG, Wu YY, and Lin M. Hyperthermia elevates cAMP levels in human epidermoid A 431 cells. Biochem. J. 276:683 689, 1991.
20. Kiang JG. Effect of intracellular pH on cytosolic free [Ca2+]i in A-431 cells. Eur. J. Pharmacol. 207(Molecular Pharmacol. Section):287-296, 1991.
21. Lin W-W, Kiang JG, and Chuang D-M. Pharmacological characterization of endothelin-stimulated phosphoinositides breakdown and cytosolic Ca2+ rise in C6 rat glioma cells. J. Neurosci., 12:1077 1085, 1992.
22. Kiang JG, Koenig ML, and Smallridge RC. Heat shock increases cytosolic free Ca2+ concentration via the Na+/Ca2+ exchange in human epidermoid A 431 cells. Am. J. Physiol. 263(Cell Physiol. 32):C30-38, 1992.
23. Smallridge RC, Gist ID, and Kiang JG. Na+-H+ antiport and monensin effects on cytosolic pH and iodide transport in FRTL 5 rat thyroid cells. Am. J. Physiol. 262(Endocrinol. Metab.) 25:E834-E839, 1992.
24. Smallridge RC, Kiang JG, Gist ID, Fein HG, and Galloway R. U 72133 inhibits TRH-induced activities in GH3 cells. Endocrinol. 131:1883 1888, 1992.
25. Kiang JG and McClain DE. Effect of heat shock, Ca2+, and cAMP on inositol 1,4,5-trisphosphate in human epidermoid A 431 cells. Am. J. Physiol. 264 (Cell Physiol. 33):C1561-C1569, 1993.
26. Aloj SM, Liguoro D, Kiang JG, and Smallridge RC. Purinergic (P2) receptor -operated calcium entry into rat thyroid cells. Biophy. Biochim. Res. Comm. 195:1-7, 1993.
27. Kiang JG. Corticotropin-releasing factor increases cytosolic free calcium via receptor-mediated Ca2+ channels. Eur. J. Pharmacol. (Molecular Pharmacol. Section) 267:135-142, 1994.
28. Kiang JG and Smallridge RC. Sodium cyanide increases cytosolic free calcium: Evidence of activation of the reversed mode of Na+/Ca2+ exchanger and Ca2+ mobilization from inositol trisphosphate-insensitive pools. Toxicol. Appl. Pharmacol., 127:173-181, 1994.
29. Kiang JG, Carr FE, Burns MR, and McClain DE. HSP-72 synthesis is promoted by increase in [Ca2+]i or activation of G proteins but not pHi or cAMP. Am. J. Physiol. 267 (Cell Physiol. 36):C104-C114, 1994.
30. Tang T, Kiang JG, and Cox BM. Opioids acting through delta-receptors increase the intracellular free calcium concentration in the dorsal root ganglion neuroblastoma hybrid ND8-47 cells. J. Pharmacol. Exptl. Ther., 270:40-46, 1994.
31. Wang X, Kiang JG, and Smallridge RC. U-73122 inhibits increases in inositol trisphosphates and cytosolic free [Ca2+] induced by TSH in FRTL-5 cells. Bioph. Biochim. Acta, 1223:101-106, 1994.
32. Poola I and Kiang JG. The estrogen inducible transferrin receptor-like membrane glycoprotein is related to stress regulated proteins. J. Biol. Chem. 269:1-8, 1994.
33. Kiang JG, Wang XD, and McClain DE. Corticotropin-releasing factor increases protein kinase C activity by elevating isoforms and at the membrane. Chin J. Physiol. 37:105-110, 1994.
34. Wang XD, Kiang JG, and Smallridge RC. Identification of protein kinase C and its multiple isoforms in Frtl-5 thyroid cells. Thyroid 5:137-140, 1995.
35. Tang T, Kiang JG, Cote T, and Cox BM. Opioid-induced increase [Ca2+]i in ND8-47 neuroblastoma X DRG hybrid cells is mediated through G protein-coupled delta opioid receptors and desensitized by chronic exposure to opioid. J. Neurochem. 65:1612-1621, 1995.
36. Kiang JG. Mystixin-7 and Mystixin-11 increase [Ca2+]i and inositol trisphosphates in human A-431 cells. Eur. J. Pharmacol. (Mol. Pharmacol. Section) 291:107-113, 1995.
37. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Heat shock protein 72 kD induction protects rat intestinal mucosa from ischemia/reperfusion injury. Gastroenterol. 109:505-515, 1995.
38. Tang T, Kiang JG, Cote T, and Cox BM. Antisense oligodeoxynucleotide to Gái2 protein á-subunit sequence inhibits an opioid-induced increase in intracellular free calcium in ND8-47 neuroblastoma x DRG hybrid cells. Mol. Pharmacol. 48:189-193, 1995.
39. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Rapid assay of HSF1 and HSF2 gene expression by reverse transcriptase PCR. Mol. Cell Biochem. 158: 48-51, 1996.
40. Ding XZ, Smallridge RC, Galloway RJ, and Kiang JG. Increases in HSF1 translocation and synthesis in human epidermoid A-431 cells: role of protein kinase C and [Ca2+]i. J. Investig. Med. 44:144-153, 1996.
41. Kiang JG, Ding XZ, and McClain DE. Thermotolerance attenuates heat-induced increases in [Ca2+]i and HSP-72 synthesis but not heat-induced intracellular acidification in human A-431 cells. J. Investig. Med. 44:189-192, 1996.
42. Kiang JG, Wang XD, Ding XZ, Gist I, and Smallridge RC. Heat shock inhibits the hypoxia-induced effects on iodide uptake and signal transduction and enhances cell survival in rat thyroid FRTL-5 cells. Thyroid, 6:475-483, 1996.
43. Wang XD, Kiang JG, Atwa MA, and Smallridge RC. Evidence for the involvement of protein kinase C isoforms in á-1 adrenergic activation of phospholipase A2 in Frtl-5 thyroid cells, J. Investig. Med. 44:566-574, 1996.
44. Kiang JG and Koenig ML. Characterization of intracellular calcium pools in thermotolerant and their desensitization in thermotolerant cells. J. Investig. Med. 44:352-361, 1996.
45. Kiang JG and Tsokos GC. Signal transduction and heat shock protein expression. J. Biomed. Sci. 3:379-388, 1996.
46. Ding XZ, Tsokos GC, Smallridge RC, and Kiang JG. Heat shock gene expression in HSP-70 and HSF1 gene-transfected human epidermoid A-431 cells. Mol. Cell. Biochem. 167:145-152, 1997.
47. Stojadinovic A, Kiang JG, Smallridge RC, Galloway RL, and Shea-Donahue T. Induction of the heat shock response limits tissue injury during acute inflammation of the rat ileum. Critical Care Medicine 25:309-317, 1997.
48. Ding XZ, Tsokos GC, and Kiang JG. Heat shock factor 1 protein in heat shock factor 1 gene-transfected human epidermoid A-431 cells requires phosphorylation prior to inducing heat shock protein-70 production. J. Clin. Investig. 99:136-143, 1997.
49. Liossis S-N, Ding XZ, Kiang JG, and Tsokos GC. Overexpression of HSP70 offers thermoprotection but enhances the TCR/CD3- and Fas-induced apoptotic death in Jurkat T-cells. J. Immunol. 158:5668-5675, 1997.
50. Kiang JG. Corticotropin-releasing factor-like peptides increase cytosolic free calcium in human epidermoid A-431 cells. Eur. J. Pharmacol. (Molecular Pharmacology Section), 329:237-244, 1997.
51. Kiang JG, Gist ID, and Tsokos GC. 17-Estradiol-induced increases in glucose-regulated proteins protect human breast cancer T47-D cells from thermal injury. Chin. J. Physiol. 40:213-219, 1997.
52. Kiang JG, Ding XZ, and McClain DE. Overexpression of HSP-70 attenuates increases in [Ca2+]i and protects human epidermoid A-431 cells after chemical hypoxia. Toxicol. Appl. Pharmacol. 149:185-194, 1998.
53. Ding XZ, Tsokos GC, and Kiang JG. Overexpression of HSP-70 inhibits the phosphorylation of HSF1 by activating protein phosphatase and inhibiting protein kinase C activity. FASEB. J. 12:451-459, 1998.
54. Kiang JG, Gist ID, and Tsokos GC. Cytoprotection and regulation of heat shock proteins induced by heat shock in human breast cancer T47-D cells: role of [Ca2+]i and protein kinases. FASEB J. 12: 1571-1579, 1998.
55. Kiang JG and Tsokos GC. Heat shock protein 70 kD family: Molecular Biology, Biochemistry, and Physiology. Pharmacol.Ther. 80:183-201, 1998.
56. Kiang JG, Ding XZ, Gist ID, and Tsokos GC. Corticotropin-releasing factor increases phosphotyrosine of phospholipase C- at tyrosine residues via its receptor 2 in human epidermoid A-431 cells. Eur. J. Pharmacol. 363:203-210, 1998.
57. Goldhill JM, Stojadinovic A, KiangJG, Smallridge RC, and Shea-Donohue T. Hyperthermia prevents functional, histological and biochemical abnormalities induced during ileitis. Neurogastroenterol. Mot. 11:69-76, 1999.
58. Kiang JG, Gist ID, and Tsokos GC. Biochemical requirement of heat shock protein 72 kD expression in human breast cancer MCF-7 cells. Mol. Cell. Biochem.199: 179-188, 1999.
59. Wang XD, Kiang JG, Scheibel LW, and Smallridge RC. Phospholipase C activation by Na+/Ca2+ exchange is essential for monensin-induced Ca2+ influx and arachidonic release in FRTL-5 thyroid cells. J. Investig. Med., 47:388-396, 1999.
60. Kiang JG and McClain DE. N-nitro-L-arginine decreases resting cytosolic [Ca2+] and enhances heat stress-induced increase in cytosolic [Ca2+] in human colon carcinoma T84 cells. Chin. J. Physiol. 42: 153-160, 1999.
61. Smallridge RC, Gist ID, Tsokos GC, and Kiang JG. Characterization of distinct heat shock and thapsigargin-induced cytoprotective proteins in FRTL-5 cells. Thyroid, 9: 1041-1047, 1999.
62. Kiang JG, Gist ID, and Tsokos GC. Heat shock induces expression of heat shock protein 72 kD and 90 kD in human breast cancer MDA-231 cells. Mol. Cell. Biochem. 204: 169-178, 2000.
63. Kiang JC and Lu PY. Biological effects of qigong and an overview of research design and methodology. Proceedings: The Science and Spirituality of Healing, 1: 99-121, 2000.
64. Kiang JG, Kiang SC, Juang Y-T, and Tsokos GC. Nω-nitro-L-arginine inhibits the inducible heat shock protein 70 kDa via Ca2+, PKC, and PKA. Am. J. Physiol. 282:G415-G423, 2002.
65. Kiang JG, Marotta D, Wirkus M, Wirkus M, and Jonas WB. External bioenergy increases intracellular free calcium concentrations and reduces cellular response to heat stress. J. Investig. Med., 50: 38-45, 2002.
66. Fleming SD, Starnes BW, Kiang JG, Stojadinovic A, Tsokos GC, and Shea-Donohue T. Heat stress protection against mesenteric ischemia/reperfusion-induced alteration in intestinal mucosa in rats. J. Appl. Physiol. 92:2600-2607, 2002.
67. Kiang JG. Genistein inhibits herbimycin A-induced inducible heat shock protein 70 kDa. Mol Cell Biochem, 245:191-199, 2003.
68. Kiang JG, McClain DE, Warke VG, Krishnan S, and Tsokos GC. Constitutive NO synthase regulates the Na+/Ca2+ exchanger in human Jurkat T cells: role of [Ca2+]i and tyrosine phosphorylation. J. Cellular Biochem., 89:1030-1043, 2003.
69. Kiang JG, Warke VG, and Tsokos GC. NaCN-induced chemical hypoxia is associated with altered gene expression. Mol Cell Biochem 254:211-216, 2003.
70. Kiang JG, Bowman DP, Wu BW, Hampton N, Kiang AG, Zhao B, Juang Y-T, Atkins JL, and Tsokos GC. Geldanmaycin inhibits hemorrhage-induced increases in caspase-3 activity, KLF6, and iNOS expression in unresuscitated organs of mice: Role of inducible HSP-70. J Appl Phsiol 97:564-569, 2004.
71. Kiang JG, Bowman PD, Zhao B, Atkins JL, and Tsokos GC. Heat shock protein-70 inducers and iNOS inhibitors as therapeutics to ameliorate hemorrhagic shock. NATO-HFM-109-P28:1-11, 2004.
72. Fleming SD, Kiang JG, and Tsokos GC. Targeting complement in treatment of ischemia/reperfusion-induced injury. NATO-HFM-109-P24:1-13, 2004.
73. Bowman PD, Zhao B, Bynum JA, Sondeen JL, Kiang JG, Dubick MA, and Atkins JL. Application of gene expression analysis with microarrays and proteinomics to the problem of hemorrhagic shock and resuscitation. NATO-HFM-109-P29:1-15, 2004.
74. Kiang JG. Inducible heat shock protein 70 kD and inducible nitric oxide synthase in hemorrhage/resuscitation-induced injury. Cell Res 14:450-459, 2004.
75. Kiang JG, Ives JH, and Jonas WB. External bioenergy-induced increases in intracellular free calcium concentrations are mediated by the Na+/Ca2+ exchanger and L-type calcium channel. Mol Cell Biochem 271:51-59, 2005.
76. Kiang JG. Lu X, Tabaku LS, Bentley TB, Atkins JL, and Tsokos GC. Resuscitation with lactated Ringers solution limits the expression of molecular events associated with lung injury after hemorrhage. J Appl Physiol 98:550-556, 2005.
77. Krishnan S, Kiang JG, Fisher CU, Nambiar MP, Nguyen HT, Kyttaris VC, Chowdhury B, Rus V, Tsokos GC. Increased caspase-3 expression and activity contributes to reduced CD3 expression in Systemic Lupus Erythematosus T cells. J Immunol 175:3417-3423, 2005.
78. Kiang JG, Bowman DP, Lu X, Li Yansong, Ding XZ, Zhao B, Juang YT, Atkins JL, Tsokos GC. Geldanmaycin treatment prevents hemorrhage-induced ATP loss in mouse organs by overexpressing HSP-70 and activating pyruvate dehydrogenase. Am J Physiol 291:G117-G127, 2006.
79. Tsen KT, Tsen SWD, Kiang JG. Lycopene is more potent than bata carotene in the neutralization of singlet oxygen: role of energy transfer probed by ultrafast Raman spectroscopy. J Biomed Optics 11:064025 (6 pages), 2006.
80. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN: Dependence on the injected carrier density. App Physics Lett 89:11211 (3 pages), 2006.
81. Tsen KT, Kiang JG, Ferry DK, Kochelap VA, Komirenko SM, Kim KW, Morkoc H. Subpicosecond Raman studies of electric-field-induced optical phonon instability in an In0.53Ga0.47As-based semiconductor nanostructure. J Phys: Condens Matter 18:7961-7974, 2006.
82. Kiang JG, Tsen KT. Biology of hypoxia. Chin J Physiol 49:223-233, 2006.
83. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Observation of the low frequency vibrational modes of bacteriophage M13 in water by Raman spectroscopy. Virology J 3:79 (11 pages), 2006.
84. Tsen KT, Dykeman E, Sankey OF, Lin N-T, Tsen S-WD, Kiang JG. Raman scattering studies of the low frequency vibrational modes of bacteriophage M13 in water. Nanotecnology 17:5474-5479, 2006.
85. Tsen KT, Kiang JG, Ferry DK, and Morkoc H. Subpicosecond time-resolved Raman studies of field-induced transient transport in an -based p-i-n semiconductor nanostructure. App Physics Lett, 89: 262101 (3 pages), 2006.
86. Tsen KT, Kiang JG, and Ferry DK. Subpicosecond transient Raman scattering studies of field-induced electron transport in an -based p-i-n nanostructure: Direct observation of the effects of electron momentum randomization. J Phys: Condens Matter 18:L585-L592, 2006.
87. Kiang JG, Peckham RM, Duke LE, Chaudry IH, Tsokos GC. Androstenediol inhibits trauma-hemorrhage-induced increase in caspase-3 by downregulating inducible nitric oxide synthase pathway. J App Physiol 102: 933-941, 2007.
88. Tsen KT, Dykeman E, Sankey OF, Tsen S-WD, Lin N-T, Kiang JG. Probing the low frequency vibrational modes of viruses with Raman scattering -- bacteriophage M13 in water. J Biomed Optics. 12: 024009 (6 pages), 2007.
89. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Subpicosecond time-resolved Raman studies of LO phonons in GaN. Proc of SPIE 6473: 64730Q-1 – 64730Q-12, 2007.
90. Tsen KT, Kiang JG, Ferry DK, Morkoc H. Studies of longitudinal optical phonons in GaN by sybpicosecond time-resolved Raman Spectroscopy. Proc of SPIE 6471: 64710X-1 – 64710X-10, 2007.
91. Kiang JG, Bowman DP, Lu X, Li Y, Wu BW, Loh HH, Tsen KT, Tsokos GC. Geldanmaycin treatment inhibits hemorrhage-induced increases in caspase-3 activity: Role of inducible nitric oxide synthase. J App Physiol 103: 1045-1055, 2007.
92. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Direct measurements of the lifetimes of longitudinal optical phonon modes and their dynamics in InN. App Physics Lett 90: 152107 (3 pages), 2007.
93. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Subpicosecond time-resolved Raman studies of electron-longitudinal optical phonon interactions in InN. App Physics Lett 90: 172108 (3 pages), 2007.
94. Tsen KT, Kiang JG, Ferry DK, Lu H, Schaff WJ, Lin HW, Gwo S. Electron-density dependence of longitudinal-optical phonon lifetime in InN studied by subpicosecond time-resolved Raman spectroscopy. J Phy Condens Matter 19: 236219 (8 pages), 2007.
95. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by coherent excitations with low power visible femtosecond laser. Virology J 4:50 (6 pages), 2007.
96. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses with a very low power visible femtosecond laser. J Physics: Condens Matter 19:322102 (9 pages), 2007.
97. Tsen KT, TsenS-W D, Chang C-L, Hung C-F, Wu T-C, Kiang JG. Inactivation of viruses by laser-driven coherent excitations via impulsive stimulated Raman scattering process. J Biomed Optics 12:064030 (6 pages), 2007.
98. Tsen KT, TsenS-W D, Sankey OF, Kiang JG. Selective inactivation of microorganisms by near-IR femosecond laser pulses. J Phy Condens Matter 19: 472201 (7 pages), 2007.
99. Kiang JG, Krishnan S, Lu X, Li Y. Inhibition of inducible nitric oxide synthase protects human T cells from hypoxia-induced injury. Mol Pharmacol 73:738-747, 2008.
100. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kiang JG. Selective inactivation of human immunodeficiency virus with subpicosecond near-infrared laser pulses. J Phys Condens matter 20:25220 (4 pages), 2008.
101. Atkins JL, Hammamiech R, Jett M, Gorbounov NV, Asher LV, Kiang JG. α-Defensin-4 and asymmetric dimethyl arginine (ADMA) increase in mesenteric lymph after hemorrhage in anesthetized rats. Shock 30: 411-146, 2008.
102. Tsen KT, Tsen S-W D, Chang C-L, Hung C-F, Wu T-C, Ramakrishna K, Mossman K, Kiang JG. Inactivation of viruses with a femtosecond laser via impulsive stimulated Raman scattering. In: Optical Interactions with Tissue and Cells XIX (edited by Steven L. Jacques, William P. Roach, Robert J. Thomas), Proc. of SPIE 6854: 68540N1-6854N10, 2008.
103. Tsen KT, Kiang JG, Ferry DK, Lu H, Scheff WJ, Lin HW, Gwo S. Dynamics of LO phonons in InN studied by subpicosecond time-resolved Raman spectroscopy. In: Ultrafast Phenomena in Semiconductors and Nanostructure Materials XII (edited by J.J. Song, K.T. Tsen, M. Betz and A. Elezzabi), Proc. of SPIE Vol. 6892: 689206 (12 pages), 2008.
104. Kiang JG, Kiang SC, Bowman PD. 17-DMAG inhibits hemorrhage-induced injury in small intestine and lung by inactivating caspase-3. International Proceedings of International Shock Congress K628C0171:23-27, 2008.
105. Tsen KT, Tsen SWD, Hung CF, Wu TC, Kibler K, Jacob B, Kiang JG. Selective inactivation of human immunodeficiency virus with an ultrashort pulsed laser. Proc. of SPIE 7175: 717510-1 – 717510-8, 2009.
106. Kiang JG, Smith JA, and Agravante NG. Geldanamycin analog 17-DMAG inhibits iNOS and caspases in gamma irradiated human T cells. Radiat Res 172: 321-330, 2009.
107. Gorbunov NV, Kiang JG. Up-regulation of Autophagy in the Small Intestine Paneth Cell in Response to Total-Body γ-Irradiation. J Pathol 219: 242-252, 2009.
108. Jiao W, Kiang JG, Cary L, Elliott TB, Pellmar TC, Ledney GD. COX-2 inhibitors are contraindicated for therapy of combined injury. Radiat Res 172: 686-697, 2009.
109. Tsen KT, Tsen S-WD, Fu Q, Lindsay SM, Kibler K, Jacobs B, Wu TC, Karanam B, Jagu S, Roden RBS, Hung C-F, Sankey OF, Ramakrishna B, Kiang JG. Photonic approach to the selective inactivation of viruses with a near-infrared subpicosecond fiber laser. J Biomed Opt 14: 064042 (10 pages), 2009.
110. Kiang JG, Jiao W, Cary L, Mog SR, Elliott TB, Pellmar TC, Ledney GD. Wound trauma increases radiation-induced mortality by increasing iNOS, cytokine concentrations, and bacterial infections. Radiate Res 173: 319-332, 2010.
111. Kiang JG, Garrison BR, Gorbunov NV. Radiation combined injury: DNA damage, apoptosis, and autophagy. Adapt Med 2: 1-10, 2010. doi: 10.4247/AM.2010.ABA004.
112. Daly MJ, Gaidamakova EK, Matrosova VY, Kiang JG, Fukumoto R, Wehr NB, Viteri G, Berlett BS, Levine RL. Small molecule proteome-shield in Deinococcus radiodurans. PLoS One 5(9): e12570 (15 pages), 2010.
113. Gorbunov NV and Kiang JG. Activation of IL-1β pathway and augmentation of Paneth cell α-defensin-4 in small intestine following total-body γ-irradiation. Intl J Immunopathol Pharmacol 23: 1111-1123, 2010.
114. Kiang JG, Smith JA, Agravante NG, Gorbunov NV. Geldanamycin analog 17-DMAG has radioprotective activity in mice. Radiat Res, in review.
115. Fukumoto R, Kiang JG. Geldanamycin analog 17-DMAG limits apoptosis in human peripheral blood cells by inhibition of p53 activation and its interaction with heat shock protein 90 kDa after ionizing radiation. Radiat Res 176: 333-345, 2011.
116. Kiang JG, Agravante NG, Smith JT, Bowman PD. 17-DMAG increases Bcl-2 and inhibits hemorrhage-induced increases in iNOS activation, caspase-3 activity and TNF-a. Cell & Bioscience 1: 21 (10 pages), 2011.
117. Tsen KT, Tsen SWD, Fu Q, Lindsay SM, Li Z, Yan H, Cope S, Vaiana S, Kiang JG. Studies of inactivation of encephalomyocaditis virus, M13 bacteriophage and Salmomella typhimurium by using a visible femtosecond laser irradiation: insight into the possible inactivation mechanisms. J Biomed Optics 16: 078003 (11 pages), 2011.
118. Whitnall MH, Cary LH, Moroni M, Ngudiankama BF, Landauer MR, Singh VK, Ghosh SP, Kulkarni S, Miller AC, Kiang JG, Srinivasan V, Xiao M. United States Armed Forces Radiobiology Research Institute countermeasures program and related policy questions. Proceedings,Hiroshima University, 2012.
119. Kiang JG, Garrison BR, Burns TM, Zhai M, Dews IC, Ney PH, Fukumoto R, Cary LH, Elliott TB, Ledney GD. Wound trauma alters ionizing radiation dose assessment. Cell Bioscience 2: 20 (12 pages), 2012.
120. Tsen S-W D, Wu TC, Kiang JG, Tsen KT. Prospects for a novel ultrashort pulsed laser technology for pathogen inactivation. J Biomed Sci 19: 62 (11 pages), 2012.
121. Kiang JG. Overview of biological effects of irradiation combined injury. NATO-HFM-223-P5:1-18, 2012.
122. Fukumoto R, Cary LH, Gorbunov NV, Elliott TB, Kiang JG. Ciprofloxacin modulates cytokine profiles, accelerates bone marrow recovery and mitigates ileum injury after radiation combined with wound trauma. PLoS One 8: e58389 (11 pages), 2013. doi: 10.1371/journal.pone.0058389. PMID: 23520506
123. Gorbunov NV, Garrison BR, McDaniel DP, Zhai M, Liao1 P-J, Nurmemet N, Kiang JG. Adaptive redox response of mesenchymal stromal cells to stimulation with lipopolysaccharide inflammagen: mechanisms of remodeling of tissue barriers in sepsis. Oxid Med Cell Longev 2013: 186795 (16 pages), 2013. doi: 10.1155/2013/186795. PMID: 23710283
124. Lu X, Nurmemet D, Bolduc DL, Elliott TB, Kiang JG. Radioprotective effects of oral 17-DMAG in mice: Bone marrow and small intestine. Cell Bioscience 3: 36 (16 pages), 2013. doi: 10.1186/2045-3701-3-36. PMID: 24499553
125. Kiang JG, Ledney GD. Skin injuries reduce survival and modulate corticosterone, C-reactive protein, complement component 3, IgM, and prostaglandin E2 after whole-body reactor-produced mixed field (n + γ-photons) irradiation. Oxid Med Cell Longev, 2013: 821541 (10 pages), 2013. doi: 10.1155/2013/821541. PMID: 24175013
126. Kiang JG, Garrison BR, Smith JT, Fukumoto R. Ciprofloxacin as a potential radio-sensitizer to tumor cells and a radioprotectant for normal cells: Differential effects on -H2AX formation, p53 phosphorylation, Bcl-2 production, and cell death. Cell Mol Biochem 393: 133-143, 2014. doi: 10.1007/s11010-014-2053-z. PMID: 24802382
127. Kiang JG, Fukumoto R. Ciprofloxacin increases survival after ionizing irradiation combined injury: gamma-H2AX formation, cytokine/chemokine, and red blood cells. Health Physics 106: 720-726, 2014. doi: 10.1097/HP.0000000000000108. PMID: 24776905
128. Fukumoto R, Burns TM, Kiang JG. Ciprofloxacin Enhances Stress Erythropoiesis in Spleen and Increases Survival after Whole-Body Irradiation Combined with Skin-Wound Trauma, PLoS One 9(2): e90448, 2014. doi: 10.1371/journal.pone.0090448. PMID: 24587369
129. Kiang JG, Zhai M, Liao P-J, Bolduc DL, Elliott TB, Gorbunov NV. Pegylated G-CSF inhibits blood cell depletion, increases platelets, blocks splenomegaly, and improves survival after whole-body ionizing irradiation but not after irradiation combined with burn. Oxid Med Cell Longev 2014: 481392 (10 pages), 2014. doi: 10.1155/2014/481392. PMID: 24738019
130. Kiang JG, Zhai M, Liao P-J, Elliott TB, Gorbunov NV. Ghrelin therapy improves survival after whole-body ionizing irradiation combined with wound or burn: Amelioration of leukocytopenia, thrombopenia, splenomegaly, and bone marrow injury. Oxid Med Cell Longev 2014: 215858, 2014. doi: 10.1155/2014/215858. PMID: 25374650
131. Gorbunov NV, Elliott TB, McDaniel DP, Zhai M, Liao P-J, Kiang JG. Mitophagy and mitochondrial remodeling in mouse mesenchymal stromal cells following a challenge with Staphylococcus epidermidis. J Cell Mol Med 19:1133-1150, 2015. doi: 10.1111/jcmm.12518. PMID: 25721260
132. Kiang JG, Gorbunov NV. Bone marrow mesenchymal stem cells increases survival after ionizing irradiation combined with wound trauma: Characterization and therapy. J Cell Sci Ther 5:190 (8 pages), 2014. doi: 10.4172/2157-7013.1000190
133. Elliott TB, Bolduc DL, Ledney GD, Kiang JG, Fatanmi OO, Wise S, Romaine PLP, Newman VL, Singh VK. Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in mice exposed to radiation and combined injury. Int J Radiat Biol 91(9):690-702, 2015. doi: 10.3109/09553002.2015.1054526. PMID: 25994812
134. Swift JM, Smith JT, Kiang JG. Ciprofloxacin therapy mitigates ATP loss after irradiation combined with wound trauma: Preservation of pyruvate dehydrogenase and inhibition of pyruvate dehydrogenase kinase 1. Radiat Res 183: 684-692, 2015. PMID: 26010714
135. Swift JM, Smith JT, Kiang JG. Hemorrhage Trauma Increases Radiation-Induced Trabecular
Bone Loss and Marrow Cell Depletion in Mice. Radiat Res 183: 578-583, 2015. doi: 10.1667/RR13960.1 PMID: 25897554
136. Swift JM, Swift SN, Smith JT, Kiang JG, Allen MR. Skin wound trauma, following high-dose radiation exposure, amplifies and prolongs skeletal tissue loss. Bone 81: 487-494, 2015. doi: 10.1016/j.bone.2015.08.022 PMID: 26335157
137. Islam A, Bolduc DL, Zhai M, Kiang JG, Swift JM. Daily Captopril Dosing Increases Survival after Whole-Body Ionizing Irradiation but Decreases Survival after in combination with Combined Burn Trauma in Mice. Radiat Res 184:273-279, 2015. doi: 10.1667/RR14113.1. PMID: 26305295
138. Kiang JG, Smith JT, Anderson MN, Swift JM, Gupta P, Balakathiresan N, Maheshwari RK. Hemorrhage exacerbates radiation effects on survival, leukocytopenia, thrombopenia, erythropenia, bone marrow cell depletion and hematopoiesis, and inflammation-associated microRNAs expression in kidney. PLoS ONE 10:e0139271, 2015. doi: 10.1371/journal.pone.0139271. PMID: 26422254
139. Klionsky DJ…Kiang JG…Zughaler SM. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12: 1-222, 2016. PMID: 26799652
140. Kiang JG. Adult mesenchymal stem cells and radiation injury. Health Phys 111:198-203, 2016. doi: 10.1097/HP.0000000000000459. PMID: 27356065
141. Gupta P, Gayen M, Smith JT, Matrosova VY, Gaidamakova EK, Daly MJ, Kiang JG, Maheshwari RK. MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation. PLoS One 11: e0160575, 2016. doi: 10.1371/journal.pone.0160575. PMID: 27500529
142. Kiang JG. Exacerbation of mild hypoxia on acute radiation syndrome and subsequent mortality. Adaptive Med 9(1): 28-33, 2017. doi: 10.4247/AM.2017.ABG170
143. Kiang JG, Zhai M, Liao P.-J., Ho C, Gorbunov NV, Elliott TB. Thrombopoietin receptor agonist mitigate hematopoietic acute radiation syndrome and improves survival after whole-body ionizing irradiation followed by wound trauma. Mediators of Inflammation 2017:7582079, 2017. doi: 10.1155/2017/7582079 PMID: 28408792
144. Kiang JG, Zhai M, Bolduc DL, Smith JT, Anderson MN, Ho C, Lin B, Jiang S. Combined therapy of pegylated-G-CSF and Alx4100TPO improves survival and mitigate acute radiation syndrome after whole-body ionizing irradiation alone and followed by wound trauma. Radiat Res 188:476-490, 2017. doi: 10.1667/RR14647.1 PMID: 28850300
145. Kiang JG, Smith JT, Anderson MN, Elliott TB, Gupta P, Balakathiresan N, Maheshwari RK, Knollmann-Ritschel B. Hemorrhage enhances cytokine, complement component 3, and caspase-3, and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury. PLoS ONE 12(9):e0184393, 2017. doi: 10.1371/journal.pone.0184393.PMID: 28934227
146. Gorbunov NV, Kiang JG. Ghrelin therapy decreases incidents of intracranial hemorrhage in mice after whole-body ionizing irradiation combined with burn trauma. Int J Mol Sci 18(8). pii: E1693, 2017. doi: 10.3390/ijms18081693. PMID: 28771181
147. Kiang JG, Smith JT, Hegge SR, Ossetrova N. Circulating cytokine/chemokine concentrations respond to ionizing radiation doses but not radiation dose rates: granulocyte-colony stimulating factor and interleukin-18. Radiat Res, in press, 2018.
148. Kiang JG, Anderson MN, Smith JT. Ghrelin therapy sustains granulocyte colony-stimulating factor and keratinocyte factor to mitigate hematopoietic syndrome and spleen after whole-body ionizing irradiation combined with wound. Cell Biosci 8:27, 2018. doi: 10.1186/s13578-018-0225-3.
149. Li X, Cui W, Hull L, Smith JT, Kiang JG, Xiao M. Effects of low-moderate doses of γ-radiation on mouse hematopoietic and immune system. Radiat Res, in review, 2018.
E-Book (1)
1. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. Cell Biology Research Progress, Nova Science Publishers, INC. Hauppauge, NY. ISBN: 978-1-62417-374-5 http://www.novapublishers.com, 2012.
Book chapters (10)
1. Yan X, Lu PY, and Kiang JG. Qigong: basic science studies in Biology. In: Healing, Intention, and Energy medicine Science, Research Methods and Clinical Implications. (Eds. WB Jonas and C Crawford) Churchill Livingstone, London, UK pp. 103-119, 2003.
2. Kiang JG and McClain DE. Heat stress. In: Combat Medicine Basic and Clinical Research in Military, Trauma, and Emergency Medicine (Eds. GC Tsokos and JL Atkins), Humana Press, New Jersey, pp. 83-101, 2003.
3. Kiang JG. Human bioenergy effects at the cellular and molecular level. In: Life and Mind In Search of Physical Basis (ed. S. Savva), Trafford Publishing, Victoria BC, Canada, pp. 117-137, 2007.
4. Tsen KT, Tsen SWD, Dykeman EC, Sankey OF, Kiang JG. Inactivation of viruses with femtosecond laser pulses. In: Contemporary Trends in Bacteriophage research (Ed: Horace T. Adams), Nova Science Publishers, NY, ISBN: 978-1-60692-181-4, pp. 151-177, 2009.
5. Kumar KS, Kiang JG, Whitnall MH, Hauer-Jensen M. Perspectives in radiological and nuclear countermeasures. In: Textbook of Military Medicine, pages 239-266, 2012.
6. Gorbunov NV, Kiang JG. Autophagy-mediated innate defense mechanism in crypt cells responding to impairment of small intestine barrier after total-body gamma-photon irradiation. In: Autophagy: Principles, Regulation and Roles in Disease (ed: Gorbunov NV), Nova Science Pulbishers, INC. Hauppauge, NY. 2012.
7. Gorbunov NV, Garrison BR, Zhai M, McDaniel DP, Ledney GD, Elliott TB, Kiang JG. Autophagy-mediated defense response of mouse mesenchymal stromal cells (MSCs) to challenge with Escherichia coli. In: Protein Interaction / Book 1; ISBN 979-953-307-577-7. Eds.: Cai J and Wang H. InTech Open Access Publisher; www.intechweb.org. pp. 23-44, 2012.
8. Kiang JG, Fukumoto R, Gorbunov NV. Lipid peroxidation after ionizing irradiation leads to apoptosis and autophagy. In: Lipid Peroxidation; ISBN 980-953-307-143-0. Eds.: Angel Catala, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp.261-278, 2012.
9. Gorbunov NV, Elliott TB, McDaniel DP, Lund K, Liao PJ, Zhai M, Kiang JG. Up-regulation of autophagy defense mechanisms in mouse mesenchymal stromal cells in response to ionizing irradiation followed by bacterial challenge. In: Autophagy, ISBN 980-953-307-971-9. Ed: Yannick Bailly, InTech Open Access Publisher: www.intechweb.org, Rijeka, Croatia. pp. 331-350, 2013.
10. Kiang JG. Characterization and therapeutic uses of adult mesenchymal stem cells. In: Stem Cell Toxicity and Medicine (ed. S.C. Sahu). Wiley & Sons, West Sussex, pp. 288-301, 2016.
Representative publications, projects, and/or deployments
- Patent 1. Method of Inhibiting Inflammatory Response, Wei ET, and Kiang JG, U.S. Patent 4,801,612 (January 31, 1989)
- Patent 2. System and method for diminishing the function of microorganisms with a visible femtosecond laser, Tsen KT, Tsen SWD, and Kiang JG, U.S. Patent 60,932,668 (June 1, 2007); South Africa Patent 2010/00380 (Sep 29. 2010); China Patent CN101971008B (May 15, 2012)
- Patent 3. 17-DMAG as a radioprotectant, Kiang JG, U.S. Provisional Patent 61,122,041 (Dec 11, 2008)
- Best Poster Award, Society of Chinese Bioscientists in America, 3-18-2017
- AFRRI Research Award, AFRRI, 2016
- Research and Development Achievements Award, U.S. Department of Army, U.S. Department of Defense, 2006
- DOD Female Science, Technology, Engineering, Mathematics Role Models, 2006
- Order of Military Medical Merit, 2006
- Outstanding Alumni Award 2005, Fu-Jen Catholic University, 2005
- The 20th Century Award for Achievement in Life Sciences, International Biographical Centre of Cambridge, England, 2000
Bibliography
- Kiang JG, Anderson MN, Smith JT. Ghrelin therapy sustains granulocyte colony-stimulating factor and keratinocyte factor to mitigate hematopoietic syndrome and spleen after whole-body ionizing irradiation combined with wound. Cell Biosci 8:27, 2018. doi: 10.1186/s13578-018-0225-3.
- Gorbunov NV, Kiang JG. Ghrelin therapy decreases incidents of intracranial hemorrhage in mice after whole-body ionizing irradiation combined with burn trauma. Int J Mol Sci 18(8). pii: E1693, 2017. doi: 10.3390/ijms18081693. PMID: 28771181
- Kiang JG, Smith JT, Anderson MN, Elliott TB, Gupta P, Balakathiresan N, Maheshwari RK, Knollmann-Ritschel B. Hemorrhage enhances cytokine, complement component 3, and caspase-3, and regulates microRNAs associated with intestinal damage after whole-body gamma-irradiation in combined injury. PLoS ONE 12(9):e0184393, 2017. doi: 10.1371/journal.pone.0184393.PMID: 28934227
- Kiang JG, Smith JT, Anderson MN, Swift JM, Gupta P, Balakathiresan N, Maheshwari RK. Hemorrhage exacerbates radiation effects on survival, leukocytopenia, thrombopenia, erythropenia, bone marrow cell depletion and hematopoiesis, and inflammation-associated microRNAs expression in kidney. PLoS ONE 10:e0139271, 2015. doi: 10.1371/journal.pone.0139271. PMID: 26422254
- Swift JM, Smith JT, Kiang JG. Ciprofloxacin therapy mitigates ATP loss after irradiation combined with wound trauma: Preservation of pyruvate dehydrogenase and inhibition of pyruvate dehydrogenase kinase 1. Radiat Res 183: 684-692, 2015. PMID: 26010714
- Kiang JG, Gorbunov NV. Bone marrow mesenchymal stem cells increases survival after ionizing irradiation combined with wound trauma: Characterization and therapy. J Cell Sci Ther 5:190 (8 pages), 2014. doi: 10.4172/2157-7013.1000190
- Kiang JG, Zhai M, Liao P-J, Elliott TB, Gorbunov NV. Ghrelin therapy improves survival after whole-body ionizing irradiation combined with wound or burn: Amelioration of leukocytopenia, thrombopenia, splenomegaly, and bone marrow injury. Oxid Med Cell Longev 2014: 215858, 2014. doi: 10.1155/2014/215858. PMID: 25374650
- Fukumoto R, Burns TM, Kiang JG. Ciprofloxacin Enhances Stress Erythropoiesis in Spleen and Increases Survival after Whole-Body Irradiation Combined with Skin-Wound Trauma, PLoS One 9(2): e90448, 2014. doi: 10.1371/journal.pone.0090448. PMID: 24587369
- Kiang JG, Jiao W, Cary L, Mog SR, Elliott TB, Pellmar TC, Ledney GD. Wound trauma increases radiation-induced mortality by increasing iNOS, cytokine concentrations, and bacterial infections. Radiate Res 173: 319-332, 2010.
- Kiang JG, Krishnan S, Lu X, Li Y. Inhibition of inducible nitric oxide synthase protects human T cells from hypoxia-induced injury. Mol Pharmacol 73:738-747, 2008.
