The mission of USU is to support the readiness of America’s Warfighter and the health and well-being of the military community by educating and developing uniformed health professionals, scientists and leaders; by conducting cutting-edge, military-relevant research, and by providing operational support to units around the world.
Since our first graduating class in 1980, the USU's MDs. Nurses and graduates in biomedical sciences provide exceptional service through service in the U.S. Military and civilian careers of distinction. Today, America's Medical School has 691 enrolled students and 5,043 graduates. Over 1,300 graduates in Biomedical Sciences lead aggressive research in medical research. Today's 663 graduates of the School of Nursing blend science, research and field training in advanced practice and PhD degrees. The USU's Postgraduate Dental College provides advanced degree's to the military's dental community, graduating 72 students since establishment.
The University's research program covers a range of clinical and other topics important to both the military and public health. Infectious diseases, trauma medicine, health maintenance, and cancer are areas of particular strength. Researchers are also making important new efforts in state-of-the-art fields that cut across disciplines, such as genomics, proteomics, and drug-delivery mechanisms.
USU is home to many different Centers and Institutes, which help advance the university's research, education and public service missions. Faculty members and students collaborate with other leading experts at USU's Centers and Institutes on projects that push incredible boundaries across manifold disciplines of biomedical science. Their work is shaping military medicine and world health in many positive, powerful ways.
The USU's military unique curriculum is supported by military professions from all services who teach USU's military and civilian students. All military personnel are supported by the USU Brigade, the Brigade staff are managed by the Military Personnel Office.
AFRRI mission is to preserve the health and performance of U.S. military personnel and to protect humankind through research that advances understanding of the effects of ionizing radiation.
To these ends, the institute collaboratively researches the biological effects of ionizing radiation and provides medical training and emergency response to manage incidents related to radiation exposure.
1987 University of North Carolina, Chapel Hill, NC Ph.D. in Neurobiology
1982 University of Rochester, Rochester, NY B.S. in Neurosciences
Dr. Armstrong is Chair of Professor of Anatomy, Physiology, and Genetics in the School of Medicine at USU. Dr. Armstrong holds secondary appointments in the Neuroscience and the Molecular and Cell Biology Graduate Programs. Dr. Armstrong received the faculty award for Outstanding Graduate Biomedical Educator from the School of Medicine in 2002. She served as Director of the USU Neuroscience Graduate Program from 2002-2008 before stepping down to establish the Center for Neuroscience and Regenerative Medicine (CNRM). The CNRM is a collaborative intramural research program of the Uniformed Services University of the Health Sciences (USU) with the National Institutes of Health (NIH) and the Walter Reed National Military Medical Center (WRNMMC). The CNRM focus is pre-clinical through clinical research to promote recovery from traumatic brain injury and to improve psychological health in combat casualties cared for at WRNMMC. Dr. Armstrong served as the Director of the CNRM from 2008-2017 and now serves as the CNRM Director of Translational Research.
Dr. Armstrong teaches in the first year medical student module on the nervous system and in several graduate student courses. Dr. Armstrong’s laboratory focuses on mechanisms of damage and repair in the brain and spinal cord. This work employs diverse research approaches, from molecular techniques to neuroimaging, to address ways to improve neuroregeneration and repair capacity in the CNS. Research efforts in her laboratory have been funded through peer-reviewed competitive awards from the NIH, the National Multiple Sclerosis Foundation, and the Department of Defense.
Dr. Armstrong’s research program has focused on cellular and molecular mechanisms of neuroregeneration. This work has taken from developmental studies and applied the techniques and approaches to examine repair after disease or injury. More specifically, her lab has extensive experience in white matter injury in multiple sclerosis models and in single and repetitive closed head injury models of mild traumatic brain injury.
Her research team uses diverse approaches including genetic mouse models, neural stem cell culture, immunohistochemistry, in situ hybridization, fluorescence imaging, magnetic resonance imaging and behavioral assessments. Our philosophy is that combining multiple independent techniques will result in more in-depth understanding and improved translational potential. Our work has also utilized collaborations to include analysis of human neuropathological specimens to validate aspects of our animal model studies.
PhD (Pharmacology) - University of Pennsylvania, Philadelphia, PA, 2005
MA (Chemistry) - Temple University, Philadelphia, PA, 2000
BS (Chemistry) - Temple University, Philadelphia, PA, 1998
The primary research goal of the lab is to identify the genetic causes and clarify the molecular mechanisms underlying neurodegenerative diseases. Using a combination of cell and molecular biology approaches we investigate how changes to cellular protein homeostasis impact human diseases.
Current research projects include (i) elucidating the signaling cascade that modulate the stability of the survival motor neuron (SMN) protein, which is deficient in spinal muscular atrophy (SMA), (ii) investigating the role of proteasome dynamics in traumatic brain injury, (iii) identifying small molecule therapeutics to treat neurological disorders using mouse models and (iv) identifying new genes associated with hereditary neurological disorders. These projects are designed to reveal novel clinical entities and therapeutic targets for treating disorders of the nervous system.
Moritz KE, McCormack NM, Abera MB, Viollet C, Yauger YJ, Sukumar G, Dalgard CL, Burnett BG. The role of the immunoproteasome in interferon--mediated microglial activation. Scientific Reports, 2017 Aug 24;7(1):9365.
Abera MB, Xiao J, Nofziger J, Titus S, Southall N, Zheng W, Moritz KE, Ferrer M, Cherry JJ, Androphy EJ, Wang A, Xu X, Austin C, Fischbeck KH, Marugan JJ, Burnett BG. ML372 blocks SMN ubiquitination and improves spinal muscular atrophy pathology in mice. JCI Insight. 2016 Nov 17;1(19):e88427.
Foran E, Kwon DY, Nofziger JH, Arnold ES, Hall MD, Fischbeck KH, Burnett BG. CNS uptake of bortezomib is enhanced by P-glycoprotein inhibition: Implications for spinal muscular atrophy. Neurobiology of Diseases. 2016; Apr;88:118-24.
Bricceno KV, Martinez T, Leikina E, Duguez S, Partridge TA, Chernomordik LV, Fischbeck KH, Sumner CJ, Burnett BG. Survival motor neuron protein deficiency impairs myotube formation by altering myogenic gene expression and focal adhesion dynamics. Human Molecular Genetics, 2014; 23(18):4745-57.
Landouré G, Zhu P, Johnson JO, Bricceno KV, Rinaldi C, Meilleur KG, Sangaré M, Diallo O, Ishiura H, Hein N, Stoll M, Britton A, Züchner S, Fink J, Nicholson G, Durr A, Stevanin G, Biesecker L for the NIH Intramural Sequencing Center, Tsuji S, Traynor BJ, Traoré M, Blackstone C, Fischbeck KH, Burnett BG: Mutation in C19orf12 causes hereditary spastic paraplegia type 43. Human Mutation, 2013; 34(10):1357-60.
Kwon DY, Dimitriadi M, Cable C, Hart AC, Chitnis A, Fischbeck KH, Burnett BG: The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein. Molecular Biology of the Cell, 2012; 24(12):1863-71.
Landouré G, Knight M, Stanescu H, Taye AA, Shi Y, Hernandez D, Elkahloun A, Vincent A, Willcox N, Kleta R, Fischbeck KH, Burnett BG: A candidate gene for autoimmune myasthenia gravis. Neurology, 2012;79:342-347.
Kwon DY, Motley WW, Fischbeck KH, Burnett BG: Increasing expression and decreasing degradation of smn ameliorate the spinal muscular atrophy phenotype in mice. Human Molecular Genetics 2011;20:3667-3677. (*cover illustration)
Chair, Council of Module Directors, USU School of Medicine, 2017-
Dean's Faculty Teaching Award, USU School of Medicine, 2016
Outstanding Civilian Educator Award, USU School of Medicine, 2013
Mears D, Pollard HB. Network science and the human brain: using graph theory to understand the brain and one of its hubs, the amygdala, in health and disease. J. Neurosci. Res. 94(6):590-605, 2016
Llanos P, Valencia M, Barrientos G, Hidalgo C, Mears D. Glucose-dependent insulin secretion in pancreatic β-cells requires Ca2+ signals generated by redox stimulation of ryanodine receptors. PLOS 1 10(6): e0129238. doi:10.1371/journal.pone.0129238, 2015
Mears D, Zimliki CL, Atwater I, RojasE, Glassman M, Leighton X, Pollard HB, Srivastava M. The Anx7(+/-) knockout mutation alters electrical and secretory responses to Ca2+-mobilizing agents in pancreatic β-cells. Cell Physiol. Biochem 29:697-704, 2012.
Verma R, Xu X, Jaiswal MK, Olsen C, Mears D, Caretti G, Galdzicki Z. In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components. Toxicol. Appl. Pharmacol. 253:178-87, 2011.
Contreras-Ferrat AE, Toro B, Bravo R, Parra V, Vásquez C, Ibarra C, Mears D, Chiong M, Jaimovich E, Klip A, Lavandero S. An inositol 1,4,5-triphosphate (IP3) receptor pathway is required for insulin-stimulated glucose transporter 4 translocation and glucose uptake in cardiomyocytes. Endocrinology 151:4665-77, 2010.
Atwater I, Guajardo M, Caviedes P, Jeffs S, Parrau D, Valencia M, Romero C, Arriagada C, Caamaño E, Salas A, Olguin F, Atlagich M, Maas R, Mears D, Rojas E. Isolation of viable porcine islets by selective osmotic shock without enzymatic digestion. Transplant Proc. 42:381-6, 2010.
Rutgers College Bachelor of Arts June 1974
New Brunswick, New Jersey
University of Wisconsin Master of Science in December 1976
Oshkosh, Wisconsin Clinical Psychology
City University of New York Master of Philosophy July 1983
New York, New York Doctor of Philosophy in
Dr. Joseph McCabe is Professor and Vice Chair for Faculty Affairs of the Department of Anatomy, Physiology and Genetics, and a Professor in the Neuroscience and the Cell and Molecular Biology Graduate Programs at USU. He received his undergraduate training in psychology and biology at Rutgers College, an M.S. degree in clinical psychology from the University of Wisconsin-Oshkosh, and M.Phil. and Ph.D. degrees from the City University of New York. Dr. McCabe spent 11 years at The Rockefeller University before his move to USU. He serves as the Co-Director, Translational Research, The Center for Neuroscience and Regenerative Medicine. His laboratory is interested in understanding the models of traumatic brain injury, behavioral testing, mechanisms of cell response to injury and aging, and in the development of pharmacological therapies that may reduce the functional consequences of brain injury.
The Rockefeller University Postdoctoral Fellow (1983-July 1985), Research Associate (July 1985-June 1987), Assistant Professor (July 1987-August 1989)
Co-Director, Translational Research, The Center for Neuroscience and Regenerative Medicine, USUHS, 2019-present
Program Director for Neuroprotection and Modeling, The Center for Neuroscience and Regenerative Medicine, USUHS, 2008-2019
Professor of Neuroscience (Secondary) August 1998-present
Professor of Molecular & Cell Biology (Secondary) August 1998-present
First recipient of the University’s, F. Edward Hébert School of Medicine, Outstanding Biomedical Graduate Educator Award, May 16, 1998
USUHS President’s Outstanding Service Medal, May 21, 2012
F. Edward Hébert School of Medicine Impact Award, 2015
McCabe JT, Moratz C, Liu Y, Burton E, Morgan A, Budinich C, Lowe D, Rosenberger J, Chen H, Liu J, Myers M. High-intensity focused ultrasound (HIFU) exposure as a model for mechanically-induced mild brain injury in mice. Ultrasound in Medicine and Biology, 2014, 40, 965-978.
Guo, H., Liu, J., VanShura, K., Chen, H., Flora, M.N., Myers, T.M., McDonough, J.H., McCabe, J.T. N-Acetyl-aspartyl-glutamate and inhibition of glutamate carboxypeptidases protects against soman-induced neuropathology. NeuroToxicology, 2015, 48, 180-191
Tucker, L.B., Fu, A.H., McCabe, J.T. Performance of male and female C57BL/6J mice on motor and cognitive tasks commonly used in pre-clinical traumatic brain injury research. Journal of Neurotrauma, 2016, 33, 880-894
Tucker, L.B., Burke, J.F., Fu, A.H., McCabe, J.T. Neuropsychiatric symptom modeling in male and female C57BL/6J mice following experimental traumatic brain injury. Journal of Neurotrauma, 2017, 34, 890-905
Tucker, L.B. and McCabe, J.T. Behavior of male and female C57BL/6J mice is more consistent with repeated trials in the elevated zero maze than in the elevated plus maze. Frontiers in Behavioural Neuroscience, 2017, 11 (Article 13) https://doi.org/10.3389/fnbeh.2017.00013
Velosky, A.G., Tucker, L.B., Fu, A.H., Liu, J., McCabe, J.T. Cognitive performance of male and female C57BL/6J mice after repetitive concussive brain injuries. Behavioural Brain Research, 2017, 324, 115-124
Kim, Y., Fu, A., Tucker, L., Liu, J. and McCabe, J.T. Characterization of controlled cortical impact devices by high speed image analysis. Journal of Neuroscience Research, 2018, 96, 501-511. https://doi.org/10.1002/jnr.24099
Vu, P.A., McNamara, E.H., Liu, J., Tucker, L.B., Fu, A.H., and McCabe, J.T. Sex differences in behavioral responses following fear conditioning and repeated bilateral frontal region closed head impacts. Brain Research, 2021, 1750, 147147. doi: 10.1016/j.brainres.2020.147147https://doi.org/10.1016/j.brainres.2020.147147
Tucker, L.B., Fu, A.H. and McCabe, J.T. Hippocampal-dependent cognitive dysfunction following repeated brain injury induced by CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration) in male and female mice. Journal of Neurotrauma, 2021. doi: 10.1089/neu.2021.0025
Nonaka, M., Taylor, W.W., Bukalo, O., Tucker, L.B., Fu, A.H., Kim, Y., McCabe, J.T. and Holmes, A. Behavioral and myelin-related abnormalities following blast-induced mild traumatic brain injury in mice. Journal of Neurotrauma, 2021. doi: 10.1089/neu.2020.7254
University Medical School, Szeged, Hungary M.D. 06/1976 Medicine
Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany and Hungarian Academy of Sciences, Budapest, Hungary Ph.D. 08/1992 Neurochemistry
Hungarian Academy of Sciences, Budapest, Hungary D.Sc. 06/1996 Medical Science
Head, Unit on Molecular Control of Neurodifferentiation, LDN, NICHD, NIH, Bethesda, MD 1992-1998
Associate Professor (tenured in 2001) Department of Anatomy, Physiology and Genetics, USUHS, Bethesda MD 1998-2012
Professor, USUHS, Bethesda, MD 2010-present
Guest Scientist, Karolinska Institute and Hospital, Stockholm, Sweden 2010-present
Understanding the complexities of traumatic brain injury: A big data approach to a big disease. Agoston DV. Behav Brain Res. 2017 May 30. pii: S0166-4328(17)30622-8.
Military Blast Injury and Chronic Neurodegeneration: Research Presentations from the 2015 International State-of-the-Science Meeting. Agoston DV et al. J Neurotrauma. 2017 Sep;34(S1):S6-S17
Modeling the Long-Term Consequences of Repeated Blast-Induced Mild Traumatic Brain Injuries. Agoston, DV. J Neurotrauma. 2017 Sep;34(S1):S44-S52.
Closed head experimental traumatic brain injury increases size and bone volume of callus in mice with concomitant tibial fracture. Brady RD et al. Sci Rep. 2016 Sep 29;6:34491
Behavioral, blood, and magnetic resonance imaging biomarkers of experimental mild traumatic brain injury. Wright DK1 et al. Sci Rep. 2016 Jun 28;6:28713
The effect of concomitant peripheral injury on traumatic brain injury pathobiology and outcome. McDonald SJ et al. J Neuroinflammation. 2016 Apr 26;13(1):90.
Modeling the Neurobehavioral Consequences of Blast-Induced Traumatic Brain Injury Spectrum Disorder and Identifying Related Biomarkers. Agoston DV and Kamnaksh A Frontiers in Neuroengineering. 2015. Chapter 23.
How to Translate Time? The Temporal Aspect of Human and Rodent Biology. Agoston, DV Front Neurol. 2017 Mar 17;8:92.
Editorial: When Physics Meets Biology; Biomechanics and Biology of Traumatic Brain Injury. Agoston DV and Skold MK. Front Neurol. 2016 Jun 15;7:91.
The Temporal Pattern of Changes in Serum Biomarker Levels Reveals Complex and Dynamically Changing Pathologies after Exposure to a Single Low-Intensity Blast in Mice. Ahmed F et al. Front Neurol. 2015 Mar 17;6:47.
Degree Year Institution Field of Study
Ph.D. 1977 University of Maryland Medical School, MD Anatomy
M.S. 1972 Pennsylvania State University, PA Zoology
B.A. 1969 Wilkes University, PA Biology
POST-GRADUATE MEDICAL EDUCATION:
Specialty Year Institution
Post-Doctoral Fellow 1976 to 1980 NINCDS, NIH
Juanita Anders is internationally recognized as an expert in Photobiomodulation research and has served as invited Chair and Speaker globally. Her specialty is peripheral and central nervous system injury and repair mechanisms, and light tissue interactions. Dr. Anders received her Ph.D. in Anatomy from the University of Maryland Medical School then joined the National Institutes of Health in the Laboratory of Neuropathology and Neuroanatomical Sciences, NINDS. She is affiliated with the Uniformed Services University of the Health Sciences as a Professor of Anatomy, Physiology and Genetics and Professor of Neuroscience. Dr. Anders serves on the Executive Councils and Scientific Advisory Boards of numerous international laser conferences. She is the past president of the North American Association of Laser Therapy, a founding member of the International Academy of Laser Medicine and Surgery, and Past President of the American Society of Lasers in Medicine and Surgery. She has recently been appointed as a board member of the International Society of Lasers in Medicine and Surgery and currently serves as the Director of the Optical Society of America Photobiomodulation Technical Group. She is a Senior Editor of Photomedicine and Laser Surgery, Associate Editor of Lasers in Surgery and Medicine, Associate Editor of Lasers in Medical Science, and on the editorial board of Physiotherapy Practice and Research and has published over 70 peer reviewed articles.
1976 -1980 Postdoctoral Fellow, Laboratory of Neuropathology and Neuroanatomical Sciences, NINCDS, NIH; 1983 -1989 Assistant Professor, Department of Anatomy, USUHS .. 1989-2006 Associate Professor, Department of Anatomy, Physiology and Genetics, USUHS; 2006 -Present Professor, Department of Anatomy, Physiology and Genetics, USUHS; 2006- Present Professor of Neuroscience (Secondary), USUHS.
2011 Harold Chaffer Trust Visiting Professorship, University of Otago, New Zealand;
2014- 2015 President of the American Society of Lasers in Medicine and Surgery; 2016 Excellence in Education Award from the American Society of Lasers for Medicine and Surgery;
The Chukuka Enwemeka Leadership Award in Photobiomodulation from the North American Association for Photobiomodulation Therapy (NAALT).
Patent: Light promotes regeneration and functional recovery after spinal cord injury US 20060036299 A1 Application number US 11/022,314 Publication date Feb 16, 2006 Inventors Juanita Anders, Ilko Ilev, Ronald Waynant, Kimberly Byrnes
Patent: Juanita J. Anders, USU and Nitto Denko Corp with USPTO (application # 61/547,267). Organic Light Emitting Diode (OLED) Low Power Light Therapy for Wound Healing (filed 2011)
Patent: Light as a Replacement for Mitogenic Factors on Progenitor Cells #067400143 JJ Anders Co-Inventor, granted full patent status. United States Patent No. 9,205,276, issued on 12/8/2015.
2003- 2014 Editorial Board, Journal of Photomedicine and Laser Surgery; 2014- Present Senior Editor of Journal of Photomedicine and Laser Surgery; 2005- Present Editorial Board, Journal of Lasers in Surgery and Medicine 2016- Present Appointed Assistant Editor of Lasers in Surgery and Medicine 2009- Present Editorial Board, Journal of Lasers in Medical Science; 2015- Present Associate Editor of Lasers in Medical Science
Holanda VM, M.C. Chavantes, X. Wu and J.J. Anders (2017) The mechanistic basis for photobiomodulation therapy of neuropathic pain by near infrared laser light. Lasers Surg. Med. 48: 653-659Published online in Wiley Online Library (wileyonlinelibrary.com) January DOI 10.1002/lsm.22628
Anders, J.J., A. K. Ketz and X. Wu (2017 Basic Principles of Photobiomodulation and Its Effects at the Cellular, Tissue, and System Levels. In: Laser Therapy in Veterinary Medicine: Photobiomodulation, First Edition. Edited by R. J. Riegel and J. C. Godbold, Jr., John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd. Chp.5: 36 -51.
Baxter, G.D., L. Liu, S. Petrich, A. Gisselman, C, Chapple, J. J. Anders and S. Tumilty (2017) Low level laser therapy (Photobiomodulation therapy) for breast cancer-related lymphedema: A systematic review. BMC Cancer 17: 833. doi: 10.1186/s12885-017-3852-x
Anders, J.J. and X. WU (2016) Comparison of light penetration of continuous wave 810 nm and super-pulsed 904 nm wavelength light in anesthetized rats. Photomed. Laser Surg., 34 (9): 1–7 DOI: 10.1089/pho.2016.4137.
Ketz, A. K., K.R. Byrnes, N. E. Grunberg, C. E. Kasper, L. Osborne, B. Pryor, N. L. Tosini, X. Wu, J.J. Anders (2017) Characterization of macrophage/microglial activation and effect of photobiomodulation in the spared nerve injury model of neuropathic pain. Pain Medicine (5): 932-946.
Holanda VM, M.C. Chavantes, D.F. Silva, C.V. de Holanda, J.O. de Oliveira Jr., X. Wu, J.J. Anders (2016) Photobiomodulation of the dorsal root ganglion for the treatment of low back pain: A pilot study. Lasers Surg. Med., 48 (7):653-659. Published first online, Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/lsm.22522.
Anders J.J., R. Lanzafame, P. R. Arany (2015) Low-Level Light/Laser Therapy Versus Photobiomodulation Therapy. Photomed. Laser Surg., 33 (4):183–184. DOI: 10.1089/pho.2015.9848. (Editorial).
Wu, X., S. Alberico, E. Saidu, S. R. Khan, S. Zheng, R. Romero, H. S. Chae, S. Li, A. Mochizuki, J.J. Anders (2015) Organic light emitting diode irradiation improves diabetic cutaneous wound healing in rats. Wound Repair and Regen.,23 (1): 104–114.
Tedford, C.E., S. DeLapp, S. Jacques and J.J. Anders (2015) Quantitative analysis of transcranial and intraparenchymal light penetration in human cadaver brain tissue. Lasers Surg. Med., 47(4): 312-322. Article first published online: 13 MAR 2015 | DOI: 10.1002/lsm.22343.
Anders J.J., H. Moges, X. Wu, I. Erbele, S. Alberico, E. Saidu, J. Smith, and B. Pryor (2014) In vitro and in vivo optimization of infrared laser treatment for injured peripheral nerves. Lasers Surg. Med., 46: 34-45.
Uniformed Services University of the Health Sciences, Bethesda, MD
1) Development of safe and effective medical countermeasures that can protect military personnel and civilians against nerve agent toxicity and lethality, including nerve agent-induced seizures, brain damage, and associated long-term morbidity.
2) Physiology and pathophysiology of the amygdala; implications for epilepsy and neuropsychiatric diseases, with emphasis on anxiety disorders, schizophrenia, and autism. 3) Mechanisms of learning and memory at the systems- and cellular/molecular level.
1991: Ph.D., Kent State University, Kent, Ohio, and Northeastern Ohio Universities College of Medicine, Rootstown, Ohio
Major: Neuroscience; Minors: Neurophysiology, Reproductive Endocrinology
Thesis Title: Long-term potentiation (LTP) and depression (LTD) in primary visual cortex of juvenile and adult rats: the role of NMDA receptors.
1987: Master’s degree, Kent State University, Kent, Ohio
Major: Exercise Physiology
Thesis Title: Effects of exogenous growth hormone and heavy-resistance exercise on rat skeletal muscle during developmental growth.
1982: B.A., University of Athens, Athens, Greece
Dr. Vassiliki Aroniadou-Anderjaska has been working for 30 years in Neuroscience research making great contributions to the fields of a) mechanisms of synaptic plasticity underlying learning and memory, and their age-dependency, b) the nature of intra-columnar and inter-columnar synaptic interactions in the cerebral cortex, c) physiology of the olfactory bulb, with high-impact discoveries such as the dendro-dendritic self-excitation of mitral cells and the presence of GABA-B heteroreceptors in the olfactory nerve terminals, and d) physiology of- and synaptic plasticity in the amygdala, with discoveries that have major implications in understanding the molecular/cellular mechanisms underlying stress and anxiety, as well as seizure generation. Since 2006, the primary aim of Dr. Aroniadou-Anderjaska’s work has been to discover novel compounds that can effectively terminate status epilepticus induced by acute nerve agent exposure, and protect against brain damage and the accompanying long-term neurological, cognitive, and emotional deficits. These research efforts have resulted in the discovery of LY293558 (Tezampanel), as a highly efficacious and safe anticonvulsant and neuroprotectant, and have led to the creation of a new company (Proniras), funded by the Biomedical Advanced Research and Development Authority (BARDA) to perform both basic and clinical studies that will advance the development of LY293558 as a new countermeasure against nerve agents.
As a PhD student (Department of Neurobiology, NEOUCOM; mentor: Dr. Timothy J. Teyler), I worked on Long-Term Potentiation (LTP) of synaptic transmission (the cellular mechanism believed to underlie learning and memory functions) in neocortical areas. I was the first to report that LTP can be induced in the visual cortex of both young and adult rats, without manipulating the neuronal circuitry by pharmacologically reducing synaptic inhibition. I found that induction of LTP in the adult neocortex was NMDA receptor-independent, and involved L-type, voltage-gated calcium channels. The importance of voltage-gated calcium channels in synaptic plasticity, in neocortical and other brain regions, was later confirmed by other investigators.
As a post-doctoral fellow (1993, Department of Anatomy, USUHS) in the laboratory of Dr. Asaf Keller, I used electrophysiological and anatomical techniques to study intra- and inter-columnar synaptic interactions and synaptic plasticity, as well as inhibitory pathways in motor and somatosensory/barrel cortex of rats and mice. I demonstrated the capacity of intrinsic synapses in motor and somatosensory cortex to undergo LTP, in both young and adult animals. My studies supported the view that more than one mechanism may participate in the induction of LTP.
As a Research Assistant Professor at the University of Maryland, School of Medicine /Department of Anatomy and Neurobiology, I studied synaptic physiology and plasticity in the rat olfactory bulb. I discovered, for the first time, the presence of GABA(B) heteroreceptors on olfactory nerve terminals. I showed that despite the absence of conventional synapses between GABAergic neurons and glutamatergic olfactory nerve terminals, the presynaptic GABA(B) heteroreceptors are activated –via a paracrine mechanism– by GABA released from juxtaglomerular cells, and mediate both tonic and phasic inhibition of sensory input to the olfactory bulb. In addition, I was the first to present evidence of dendrodendritic self-excitation of mitral cells in the olfactory bulb; this finding provided strong support to the emerging realization that neuronal communication is effected not only via conventional synapses, but also via autocrine and paracrine actions of neurotransmitters (including “fast neurotransmitters” like glutamate).
In 2000, I joined the Department of Psychiatry at USUHS, where my research focus has been in the amygdala, the brain structure that plays a most central role in epilepsy, as well as in emotional behavior and neuropsychiatric diseases. I was the first to demonstrate that field potentials can be recorded from the amygdala, in in vitro brain slices, despite that this structure does not have a laminar organization, and, therefore, it does not generate strong extracellular current dipoles during population activity. Using this preparation, I demonstrated the capacity of the external capsule to basolateral amygdala (BLA) synapses to undergo input-specific LTP and depotentiation. In 2001, in collaboration with Dr. Maria Braga and Dr. He Li, we discovered a novel effect of the anticonvulsant lamotrigine in the amygdala, which could explain the effectiveness of this drug in certain psychiatric illnesses. Our studies on the modulation of GABA release by presynaptic GluK1 (GluR5) kainate receptors in the BLA were part of our efforts to understand the mechanisms regulating neuronal excitability in this brain region, which is central to seizure generation/epilepsy, as well as emotional disorders such as PTSD. Our finding of the reduction of the α1A adrenoceptor-mediated facilitation of GABAergic transmission in the BLA following exposure to stress, provided important insights into the mechanisms that may underlie the hyperexcitability of the amygdala in certain stress-related disorders such as PTSD, the antiepileptogenic effects of norepinephrine in temporal lobe epilepsy, and the stress-induced exacerbation of seizure activity in epileptic patients.
My most recent research efforts, in collaboration with Dr. Braga, have been focused on finding effective antidotes against nerve agent-induced seizures and brain damage. The discoveries from this research have been exceptionally promising and may soon lead to FDA approval of a new anticonvulsant and neuroprotectant against nerve agents, that is effective even if administered with a delay after the exposure; anticonvulsant efficacy at delayed post-exposure time points is particularly important considering that control and monitoring of status epilepticus by medical personnel may not be immediately available in an emergency situation with mass casualties. At the same time, we continue research on the physiology and pathophysiology of the amygdala, with an emphasis on the mechanisms regulating neuronal excitability in the BLA (abnormal excitability of the BLA network is a characteristic feature in anxiety disorders). We have found that activation of GluK1 kainate receptors in the rat BLA facilitates both GABA and glutamate release, but the facilitation of glutamate release prevails, and, therefore, activation of these receptors can have an anxiogenic and seizurogenic net function. In contrast, we found that α(7)-containing nicotinic acetylcholine receptors are active in the basal state enhancing GABAergic inhibition, and their further exogenous activation produces a transient but dramatic increase of spontaneous inhibitory postsynaptic currents in principal BLA neurons, which may underlie the anxiolytic effects of nicotine. We further demonstrated that acid-sensing ion channels (ASICs) also contribute significantly to inhibition of the BLA in the basal state, and activation of these channels produces anxiolytic effects. Most recently, we discovered that the NMDA receptor subtype that contains the GluN2A subunit plays a central role in the regulation of rhythmic inhibition in the BLA, a finding with potentially significant implications for the treatment of schizophrenia, autism, and depressive disorders.
Aroniadou-Anderjaska V, Figueiredo TH, Apland JP, Prager EM, Pidoplichko VI, Miller SL, Braga MF. (2016) Long-term neuropathological and behavioral impairments after exposure to nerve agents. Ann N Y Acad Sci. 1374(1):17-28.
Miller SL, Aroniadou-Anderjaska V, Figueiredo TH, Prager EM, Almeida-Suhett CP, Apland JP, Braga MF. (2015) A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists. Toxicol Appl Pharmacol. 284:204-216
Apland JP, Aroniadou-Anderjaska V, Figueiredo TH, Rossetti F, Miller SL, Braga MF. (2014) The Limitations of Diazepam as a Treatment for Nerve Agent-Induced Seizures and Neuropathology in Rats: Comparison with UBP302. J Pharmacol Exp Ther. 351:359-72.
Apland JP, Aroniadou-Anderjaska V, Figueiredo TH, Green CE, Swezey RR, Yang C, Qashu F, Braga MF (2013) Efficacy of the GluK1/AMPA Receptor Antagonist LY293558 Against Seizures and Neuropathology in a Soman-Exposure Model without Pretreatment and its Pharmacokinetics after Intramuscular Administration. J Pharmacol Exp Ther. 344:133-40
Figueiredo TH, Aroniadou-Anderjaska V, Qashu F, Apland JP, Pidoplichko V, Stevens D, Ferrara TM, Braga MFM (2011) Neuroprotective efficacy of caramiphen against soman and mechanisms of action. British J. Pharmacol., 164:1495-505.
Williams LR, Aroniadou-Anderjaska V, Qashu F, Finne H, Pidoplichko V, Bannon DI, and Braga MFM. (2011) RDX Binds to the GABAA Receptor-Convulsant Site and Blocks GABAA Receptor-Mediated Currents in the Amygdala: a Mechanism for RDX-Induced Seizures. Environmental Health Perspectives. 119:357-363.
Aroniadou-Anderjaska V, Figueiredo TH, Apland JP, Qashu F, Braga MF. (2009) Primary brain targets of nerve agents: the role of the amygdala in comparison to the hippocampus. Neurotoxicology 30:772-6.
Braga, M.F.M., Aroniadou-Anderjaska, V., Manion, S.T., Hough, CJ and Li, H. (2004) Stress impairs alpha1A adrenoceptor-mediated noradrenergic facilitation of GABAergic transmission in the basolateral amygdala. Neuropsychopharmacology. Vol. 29, 45-58.
Braga, M.F.M., Aroniadou-Anderjaska, V., Xie, J. and Li, H. (2003) Bidirectional modulation of GABA release by presynaptic GluR5 kainate receptors in the basolateral amygdala. Journal of Neuroscience. Vol 23, 442-452.
Braga, M.F.M., Aroniadou-Anderjaska, V., Post, R.M. and Li H. (2002) Lamotrigine reduces spontaneous and evoked GABAA receptor-mediated synaptic transmission in the basolateral amygdala: Implications for its effects in seizure- and affective disorders. Neuropharmacology, 42, 522-529.
Aroniadou-Anderjaska V, Pidoplichko VI, Figueiredo TH, Braga MFM. (2018) Oscillatory Synchronous Inhibition in the Basolateral Amygdala and its Primary Dependence on NR2A-containing NMDA Receptors. Neuroscience, 373:145-158.
Pidoplichko V†, Aroniadou-Anderjaska V†, Prager EM, Figueiredo TH, Almeida-Suhett CP, Miller S, and Braga MFM. (2014). ASIC1a activation enhances inhibition in the basolateral amygdala and reduces anxiety. J Neurosci. 34(9):3130-41. (The Journal of Neuroscience had a Press Release based on the findings of our paper) †shared first authorship
Aroniadou-Anderjaska V, Brita Fritsch, Felicia Qashu and Maria F.M. Braga (2008) Pathology and Pathophysiology of the Amygdala in Epileptogenesis and Epilepsy. Epilepsy Research, 78(2-3):102-16.
Aroniadou-Anderjaska V, Pidoplichko V, Figueiredo TH, Almeida-Suhett CP, Prager EM, and Braga MFM. (2012) Presynaptic Facilitation of Glutamate Release in the Basolateral Amygdala: a Mechanism for the Anxiogenic and Seizurogenic Function of GluK1 receptors. Neuroscience. 221:157-169
Aroniadou-Anderjaska V, Felicia Qashu and Maria F.M. Braga (2007) Mechanisms Regulating GABAergic Inhibitory Transmission in the Basolateral Amygdala: Implications for Epilepsy and Anxiety Disorders. Amino Acids, 32:305-15
Aroniadou-Anderjaska, V., Zhou FM, Priest CA, Ennis , M. and Shipley M.T. (2000) Tonic and synaptically evoked presynaptic inhibition of sensory input to the rat olfactory bulb via GABA-B heteroreceptors. J. Neurophysiol., 84, 1194-1203.
Aroniadou-Anderjaska, V., Ennis , M. and Shipley M.T. (1999) Dendrodendritic recurrent excitation in mitral cells of the rat olfactory bulb. J. Neurophysiol. , 82, 489-494.
Aroniadou-Anderjaska, V., Ennis , M. and Shipley M.T. (1999) Current Source Density analysis in the rat olfactory bulb: Laminar distribution of kainate/AMPA and NMDA receptor-mediated currents. J. Neurophysiol., 81, 15-29.
Aroniadou, V.A. and Keller, A. (1995) Mechanisms of LTP induction in rat motor cortex in vitro. Cerebral Cortex, 5, 353-362.
Aroniadou, V.A. and Keller A. (1993) The patterns and synaptic properties of horizontal intracortical connections in the rat motor cortex. J. Neurophysiol., 70, 1553-1569.
Chronic diseases and even aging itself are known to damage the body by dys-regulated inflammatory processes. Dysregulated expression of the pro-inflammatory cytokine and chemokine genes are known to contribute to chronic inflammatory diseases. Recently, endogenous non-coding RNA (ncRNA) molecules, including long non-coding RNAs (LncRNAs) and microRNAs (miRNAs, miRs) have emerged as important targets in the frontier of biomedical research. These non-coding RNAs have been proven to be key regulators of gene expression. The ability to detect non-coding RNAs in biofluids has highlighted their usefulness as non-invasive markers of diseases, including lung diseases. The expression of specific non-coding RNAs is altered in many lung diseases and their levels in the circulation often reflect the changes in expression of their lung-specific counterparts. Therefore, exploiting these biomolecules as diagnostic tools seems an obvious goal. Our goal is to investigate the role of non-coding RNAs in Cystic Fibrosis lung disease and develop novel anti-inflammatory therapeutics for pulmonary disorders.
D.D.S. Federal University of Alagoas, Brazil
Ph.D. Department of Physiology and Pharmacology, University of Strathclyde, Scotland, UK
Post Doctoral Fellow, University of Maryland School of Medicine, USA
The amygdala, an almond-shaped structure in the midtemporal lobe, plays a central role in emotional behavior, as well as in modulating cognitive functions. Thus, the amygdala is a key component of the brain's neuronal networks that determine the emotional significance of external -and internal- events. Via reciprocal connections with the prefrontal cortex, the amygdala provides a neurobiological substrate through which emotions affect cognition (and vice versa). Via reciprocal connections with the hippocampus, as well as with other cortical and subcortical areas, the amygdala modulates memory functions, and mediates certain forms of memory. Furthermore, via efferent pathways to the hypothalamus, the amygdala can trigger the autonomic and endocrine cascades associated with the response to a stressful event. It is not surprising therefore, that many emotional/psychiatric disorders are associated with dysfunction of the amygdala. For example, anxiety disorders are associated with a hyperactive and/or hyperexcitable amygdala. One goal of the research program in our laboratory is to understand the mechanisms regulating neuronal excitability in the amygdala, and the alterations in these mechanisms in anxiety disorders. As the GABAergic and glutamatergic system are the primary determinants of neuronal excitability in the brain, we are using electrophysiological techniques (whole-cell patch-clamp, intracellular and field potential recordings), as well as molecular methods, to study the modulation of GABAergic and glutamatergic synaptic transmission in the amygdala of normal and fear-conditioned rats and mice. We also study plasticity of glutamatergic synaptic transmission (Long-Term Potentiation, LTP) in these animals, as LTP is considered to be the cellular mechanism for acquiring and consolidating information, and therefore alterations in synaptic plasticity can have a profound effect on the function of a brain region.
In addition to its role in emotional disorders, the amygdala also plays a central role in epilepsy. The basolateral nucleus of the amygdala (BLA), in particular, is highly prone to generating seizure activity, and, in many models of epilepsy, it is the focal point from where epileptic activity is spread to other brain areas, culminating in status epilepticus. The second research goal in our laboratory is to understand the role of the amygdala in epileptogenesis. Epileptogenesis is the process whereby, after an acute brain insult, such as traumatic brain injury, progressive pathophysiological alterations in neuronal networks occur that lead to the development of epilepsy. We recently identified an important mechanism regulating neuronal excitability and epileptic activity in BLA. We demonstrated that, in the rat BLA, kainate receptors containing the GluR5 subunit (GluR5KRs) regulate GABAergic inhibitory synaptic transmission via both postsynaptic and presynaptic mechanisms. The relevance of these findings to epilepsy is suggested by additional findings that a) activation of GluR5KRs can induce epileptiform activity in in vitro amygdala slices, and epilepsy in vivo, b) expression of these receptors is elevated in epileptic temporal lobe regions, in both humans and rats, c) GluR5-KRs are a primary target of a commonly used antiepileptic drug (topiramate), and d) GluR5-KR antagonists prevent limbic seizures. We are working on identifying the alterations in GABAergic and glutamatergic synaptic transmission, in the BLA, during the course of epileptogenesis, and determining whether changes in the function of GluR5KRs contribute to these alterations. We will also determine whether genetic elimination or pharmacological blockade of GluR5KRs can inhibit epileptogenesis. Unraveling the role of GluR5KRs in the pathogenesis of epilepsy may have significant implications for the discovery of antiepileptogenic drugs that have fewer side effects, as GluR5KR antagonist do not affect normal synaptic transmission and GluR5KRs are not widely distributed in the brain.
In summary, the goal of our research program is to provide the basic knowledge that is necessary for the development of effective therapeutic strategies aimed at preventing or treating certain neurological and psychiatric disorders where dysfunction of the amygdala plays a pivotal, causative role.
Project 1: INCREASING BRAIN ACIDITY MAY REDUCE ANXIETY - Animal study highlights potential new target for treating anxiety disorders
The lifetime prevalence of anxiety disorders (generalized anxiety disorder, panic disorder, social phobia, posttraumatic stress disorder, and obsessive-compulsive disorder) is already more than 20% in the general population, and it is only rising. The associated personal and societal burden is considerable. Available psychotropic drug treatments require careful selection and close patient monitoring, and are often ineffective or have serious adverse effects. Dr. Maria Braga and colleagues (APG USUHS) reported a novel mechanism associated with the generation and expression of anxiety, which may potentially lead to the development of new pharmacological treatments for anxiety disorders (The Journal of Neuroscience, 2014 Feb 26;34(9):3130-41).
This study was performed in Dr. Braga’s lab at USU with the participation of 3 neuroscience graduate students*, and was authored by Pidoplichko VI, Aroniadou-Anderjaska V, Prager EM*, Figueiredo TH, Almeida-Suhett CP*, Miller SL*, and Braga MFM. The Society for Neuroscience covered their paper entitled "ASIC1a Activation Enhances Inhibition in the Basolateral Amygdala and Reduces Anxiety" in a press release. The Press Release was also published in ScienceDaily which is one of the Internet's most popular science news web sites. Since starting in 1995, this award-winning site has earned the loyalty of students, researchers, healthcare professionals, government agencies, educators and the general public around the world. Now with more than 3 million monthly visitors, ScienceDaily generates nearly 15 million page views a month and is steadily growing in its global audience. Please see the press release at https://www.eurekalert.org/pub_releases/2014-02/sfn-iba022414.php or you may also contact Dr. Maria Braga to request a pdf copy of the SFN press release.
Below, please find other articles published by Maria's team elucidating new and important mechanisms regulating neuronal excitability in the amygdala, and the discussion of how alterations in these mechanisms play a critical role in anxiety disorders and epilepsy.
NIH Sponsored Selected Publications:
Pidoplichko VI, Aroniadou-Anderjaska V, Prager EM, Figueiredo TH, Almeida-Suhett CP, Miller SL, Braga MF. ASIC1a activation enhances inhibition in the basolateral amygdala and reduces anxiety. J Neurosci. 2014 Feb 26;34(9):3130-41.
Aroniadou-Anderjaska V, Pidoplichko VI, Figueiredo TH, Braga MFM. Oscillatory Synchronous Inhibition in the Basolateral Amygdala and its Primary Dependence on NR2A-containing NMDA Receptors. Neuroscience. 2018 Mar 1;373:145-158.
Pidoplichko VI, Prager EM, Aroniadou-Anderjaska V, Braga MF. α7-Containing nicotinic acetylcholine receptors on interneurons of the basolateral amygdala and their role in the regulation of the network excitability. J Neurophysiol. 2013 Nov;110(10):2358-69.
Aroniadou-Anderjaska V, Pidoplichko VI, Figueiredo TH, Almeida-Suhett CP, Prager EM, Braga MF. Presynaptic facilitation of glutamate release in the basolateral amygdala: a mechanism for the anxiogenic and seizurogenic function of GluK1 receptors. Neuroscience. 2012 Sep 27;221:157-69.
Williams LR, Aroniadou-Anderjaska V, Qashu F, Finne H, Pidoplichko V, Bannon DI, Braga MF. RDX binds to the GABA(A) receptor-convulsant site and blocks GABA(A) receptor-mediated currents in the amygdala: a mechanism for RDX-induced seizures. Environ Health Perspect. 2011 Mar;119(3):357-63.
PROJECT 2: EBBING GABA SUPPLY EXPLAINS WHY MILD TRAUMATIC BRAIN INJURY EFFECTS SLOW TO SHOW
About three quarters of people who suffer mild traumatic brain injury (mTBI)—such as soldiers who survive explosive device blasts and athletes concussed on the playing field—experience memory loss, lack of concentration, increases in anxiety, and changes in hippocampal function, even where no structural damage can be seen. In a consortium organized and led by Dr. Maria Braga (APG - USUSH) through the multi-institutional Center for Neuroscience and Regenerative Medicine (CNRM), research teams from the NIMH (Lee Eiden, PhD, Chief, Section on Molecular Neuroscience and Zheng Li, PhD, Chief, Section on Synapse Development Plasticity) and the Uniformed Services University of the Health Sciences (USUHS) (Maria F. Braga, DDS, PhD and Ann Marini, PhD, MD) have worked together to refine our understanding of how mTBI affects the brain. Working with rat models, the researchers were able to show that even one incident of mild controlled cortical impact (mCCI) can affect inhibitory interneurons’ ability to biosynthesize GABA. The resultant decrease in GABAergic tone subsequently disrupted synaptic transmission, which in turn increased anxiety. The experimenters further demonstrated that, because the loss of GABAergic function is gradual, the effects are frequently not observed until some time after an mTBI incident. These findings suggest that bolstering GABAergic neuronal function could possibly slow or even reverse deleterious changes that occur following mTBI.
Additionally, the USUHS and NIMH researchers used multi-read miRNA analysis (Dr. Li’s lab) and transcriptome microarray analysis, carried out by NIMH post-bac IRTA Cameron Waites (Pat Tilmon Scholar in residence 2013-2015; now completing medical training at Massachusetts General Hospital, Boston) to show that mCCI is immediately followed by cytokine-associated changes in non-neuronal brain compartments and in neuronal miRNA—changes that may be linked to later effects of mTBI on neuronal transmission. If the consortium receives support to continue its study of TBI, the researchers propose to test precisely how initial insult to the brain is linked neurochemically with the cascade that leads to decreased GABAergic function over a period of days, and to altered emotion and behavior over a period of weeks. Establishing and understanding causal links such as these is a first step toward the development of more effective treatments—and perhaps even to reversing adverse neuronal effects of traumatic brain injury.
This Research Program was described in an article in BrainWaves (2016), the NIMH in-house organ for disseminating information about intramural research, including collaborative research. You may contact Maria Braga to request a pdf copy of the BrainWaves article.
USUHS-NIMH CNRM-Sponsored Publications:
Figueiredo TH, Harbert CL, Pidoplichko V, Almeida-Suhett CP, Pan H, Rossetti K, Braga MFM, Marini AM. Alpha-Linolenic Acid Treatment Reduces the Contusion and Prevents the Development of Anxiety-Like Behavior Induced by a Mild Traumatic Brain Injury in Rats. Mol Neurobiol. 2018 Jan;55 (1):187-200.
Camila P. Almeida-Suhett, Eric M. Prager, Volodymyr Pidoplichko, Taiza H. Figueiredo, Ann M. Marini, Zheng Li, Lee E. Eiden, Maria F. M. Braga. GABAergic Interneuronal Loss and Reduced Inhibitory Synaptic Transmission in the Hippocampal CA1 Region after Mild Traumatic Brain Injury. Experimental Neurology Nov 2015(273):11–23.
Samal BB, Waites CK, Almeida-Suhett C, Li Z, Marini AM, Samal NR, Elkahloun A, Braga MF, Eiden LE. Acute Response of the Hippocampal Transcriptome Following Mild Traumatic Brain Injury After Controlled Cortical Impact in the Rat J Mol Neurosci. Oct 2015 (57)2:282-303.
Almeida-Suhett CP, Prager EM, Pidoplichko V, Figueiredo TH, Marini AM, Li Z, Eiden LE, Braga MF. Reduced GABAergic Inhibition in the Basolateral Amygdala and the Development of Anxiety-like Behaviors after Mild Traumatic Brain Injury. PLoS One. Jul 21, 2014(9)7:e102627.
Camila P. Almeida-Suhett, Zheng Li, Ann M. Marini, Maria F.M. Braga, and Lee E. Eiden.
Temporal Course of Changes in Gene Expression Suggests a Cytokine-Related Mechanism for Long-Term Hippocampal Alteration after Controlled Cortical Impact. J Neurotrauma Apr 1 2014 (31)7:683-690.
Zhonghua Hu, Danni Yu, Camila Almeida-Suhett, Kang Tu, Ann M. Marini, Lee Eiden,
Maria F. Braga, Jun Zhu, Zheng Li. Expression of miRNAs and Their Cooperative Regulation of the Pathophysiology in Traumatic Brain Injury. PLoS One 2012(7)6:e39357.
PROJECT 3: NEW DRUG STRIKES NERVE AGENT
Nerve agents are deadly chemical weapons that are presently a serious threat to military and civilian populations. Nerve agents have been used in the Iraq-Iran war, against Kurdish civilians, in terrorist attacks in Japan, and most recently, the world has witnessed, once again, the devastating effects of nerve agent attacks against civilians in Syria and in England. Currently FDA-approved medical countermeasures are inadequate in counteracting many of the acute intoxication symptoms, including arresting nerve agent-induced seizures (status epilepticus), and preventing brain damage, which leads to long-term neurological and neuropsychiatric disorders. Dr. Maria Braga and colleagues (APG USUHS) has discovered that Tezampanel (also known as LY- 293,558), an antagonist of the GluK1 Kainate Receptors and AMPA receptors, is very effective against nerve agent-induced seizures and neuropathology. Maria Braga conceived the initial idea in 2006, and obtained support from the National Institute of Neurological Disorders and Stroke (NINDS) to demonstrate the proof-of-concept. Since then, and with continuous support from NINDS, Maria and her team have conducted extensive pre-clinical studies demonstrating the effectiveness of Tezampanel against these weapons of mass destruction, even when the drug was administered with a significant delay after exposure to a nerve agent. Encouraged by the very promising results of her investigations, Maria convinced Eli Lilly to form a new company (Proniras) to further develop Tezampanel. On Friday, April 25, 2018, it was announced that the Biomedical Advanced Research and Development Authority (BARDA) has awarded a $89.5 million contract to Proniras for the advanced research development of Tezampanel (also known as LY- 293,558), for the treatment of nerve agent induced-seizures that are refractory to benzodiazepines. These further studies are likely to result in the development of a novel, safe and effective therapeutic treatment against nerve agent-induced seizures and brain damage that will enhance our treatment response capabilities during an emergency.
This Research Program was described in an article in DVIDS – Defense Visual Information Distribution Service (2018). DVIDS is a state-of-the-art, 24/7 operation owned by DMA (Defense Media Activity) that provides a timely, accurate and reliable connection between the media around the world and the military serving at home and abroad. Please see the press release at https://www.dvidshub.net/news/289618/new-drug-strikes-nerve-agent or you may contact Maria Braga to request a pdf copy of the DVIDS article.
NIH/DTRA Sponsored Selected Publications:
Figueiredo TH, Apland JP, Braga MFM, Marini AM. Acute and long-term consequences of exposure to organophosphate nerve agents in humans. Epilepsia. 2018 Oct;59 Suppl 2:92-99.
Apland JP, Aroniadou-Anderjaska V, Figueiredo TH, Pidoplichko VI, Rossetti K, Braga MFM. Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population. J Pharmacol Exp Ther. 2018 May;365(2):314-326
Aroniadou-Anderjaska V, Figueiredo TH, Apland JP, Prager EM, Pidoplichko VI, Miller SL, Braga MF. Long-term neuropathological and behavioral impairments after exposure to nerve agents. Ann N Y Acad Sci. 2016 Jun;1374(1):17-28.
Prager EM, Aroniadou-Anderjaska V, Almeida-Suhett CP, Figueiredo TH, Apland JP, Rossetti F, Olsen CH, Braga MF. The recovery of acetylcholinesterase activity and the progression of neuropathological and pathophysiological alterations in the rat basolateral amygdala after soman-induced status epilepticus: relation to anxiety-like behavior. Neuropharmacology. 2014 Jun;81:64-74.
Prager EM, Figueiredo TH, Long RP 2nd, Aroniadou-Anderjaska V, Apland JP, Braga MF. LY293558 prevents soman-induced pathophysiological alterations in the basolateral amygdala and the development of anxiety. Neuropharmacology. 2015 Feb;89:11-8.
Prager EM, Pidoplichko VI, Aroniadou-Anderjaska V, Apland JP, Braga MF. Pathophysiological mechanisms underlying increased anxiety after soman exposure: reduced GABAergic inhibition in the basolateral amygdala. Neurotoxicology. 2014 Sep;44:335-43
Figueiredo TH, Aroniadou-Anderjaska V, Qashu F, Apland JP, Pidoplichko V, Stevens D, Ferrara TM, Braga MF. Neuroprotective efficacy of caramiphen against soman and mechanisms of its action. British Journal of Pharmacology 2011 Nov;164(5):1495-505.
1963 B.A. (Physics, Math minor), San Diego State College, San Diego, California
1965 M.S. (Physics), San Diego State College, San Diego, California
1973 Ph.D. (Physics), University of Arizona, Tucson, Arizona
1965 , NASA Graduate Traineeship , University of Arizona, Department of Physics
1972, NIH Post Doctoral Trainee and NIH Post Doctoral Fellow, University of Arizona, College of Medicine, Department of Physiology
1976, Research Associate, Marine Biomedical Institute of University of Texas Medical Branch at Galveston, Texas
1978, Assistant Professor, Department of Physiology, Uniformed Services University of the Health Sciences, Bethesda, MD.
1985, Associate Professor, Department of Physiology, F. Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD.
2000, Associate Professor, Department of Anatomy, Physiology & Genetics, F. Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD
Helina Moges, Xingjia Wu, Jennifer McCoy, M. Vasconcelos, Howard Bryant, Neil E. Grunberg and Juanita J. Anders. Effect of 810 nm Light on Nerve Regeneration After Autograft Repair of Severely Injured Rat Median Nerve. Lasers in Surgery and Medicine, Vol 43, Num 9, 901 - 906, Nov ( 2011).
Donald D. Rigamonti, Howard J. Bryant, Osvaldo Bustos, Leon Moore, Helene M. Hoffman. Implementing Anatomic VisualizeR Learning Modules in Anatomy Education, In: The Third Visible Human Project Conference Proceedings, R.A. Banvard, Ed. (ISSN 1524-9008, Published as a CD.) (2000)
Haddy, F.J., Pamnani, M.B., and Bryant, H.J. Cardiovascular actions of 6-iodo-amiloride. In: Diuretics II Chemistry, Pharmacology and Clinical Applications, Ed. J.B. Puschett, P. 629-631 (1987)
Gruener, R., Bryant, H.J., Markovitz, D., Huxtable, R. and Bressler, R. Ionic actions of taurine on nerve and muscle membranes: Electrophysiologic studies. In: Taurine, Ed. R. Huxtable and A. Barbeau, Raven Press, New York, (1976)
Von Leden RE, Khayrullina G, Moritz KE, Byrnes KR. Age exacerbates microglial activation, oxidative stress, inflammatory and NOX2 gene expression, and delays functional recovery in a rodent model of spinal cord injury. J Neuroinflammation; 2017, In Press.
Brabazon F, Wilson CM, Jaiswal S, Frey WH II, Byrnes KR. Intranasal insulin treatment of an experimental model of moderate traumatic brain injury. J Cerebral Blood Flow Metab, 2017. In Press.
Reed JR, Grillakis A, Kline A, Byrnes KR. Gait Analysis in a Rat Model of Traumatic Brain Injury. Behavioural Brain Res. In press 2021.
Yauger YJ, Bermudez S, Moritz KE, Glaser E, Stoica B, Byrnes KR. Iron accentuated reactive oxygen species release by NADPH oxidase in activated microglia contributes to oxidative stress in vitro. J Neuroinflammation. 2019; 16(1):41. PMID: 30777083
von Leden RE, Selwyn RG, Jaiswal S, Wilson CM, Khayrullina G, Byrnes KR. 18F-FDG PET imaging of injured rat spinal cord reveals depressed glucose uptake correlating with lesion volume and functional recovery. Neurosci Letters. 2016; 621:126-32.
Selwyn RG, Cooney SJ, Khayrullina G, Hockenbury N, Wilson CM, Jaiswal S, Bermudez S, Armstrong RC, Byrnes KR. Outcome after repetitive mild traumatic brain injury is temporally related to glucose uptake profile at time of second injury. J Neurotrauma. 2016; 33:1479-91.
Khayrullina G, Bermudez S, Byrnes KR. Inhibition of NOX2 reduces locomotor impairment, inflammation and oxidative stress after spinal cord injury. J Neuroinflammation. 2015, 12:172.
Jaiswal S, Hockenbury N, Pan H, Knutsen A, Dardzinski BJ, Byrnes KR. Alteration of FDG uptake by performing novel object recognition task in a rat model of traumatic brain injury. Neuroimage: 2019;188:419-426. PMID:30576849
Brabazon F, Bermudez S, Khayrullina G, Byrnes KR. The effects of insulin on the inflammatory action and polarization of BV2 microglia. PlosOne: 2018;13(8):e0201878. PMID: 30148836
von Leden RE, Moritz KE, Bermudez S, Jaiswal S, Wilson CM, Dardzinski BJ, Byrnes KR. Aging alters the glucose uptake pathway in the naïve and injured rodent spinal cord. Neurosci Lett: 2019;690:23-28. PMID: 30296507
2005 Ph.D., Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD
2002 A.S., Computer Science, emphasis in Bioinformatics, Foothill College, Los Altos, CA
1999 certification, Medical Laboratory Technician, Army Medical Department Center and School, Fort Sam Houston, TX
1997 B.A., Molecular and Cellular Biology, emphasis in Neurobiology, University of California, Berkeley, CA
1979-1983 B.S. in Biology, Houghton College, Houghton, NY
1983-1990 M.D.-Ph.D., Duke University School of Medicine, Duke University Graduate School, Department of Cell Biology, Durham, NC,
1990-1991 Medicine Internship, UNC Hospitals, Chapel Hill, NC
1991-1994 Dermatology Residency, Duke University Medical Center, Durham, NC
1994-1996 Clinical Associate, Dermatology Branch, NIH, Bethesda, MD
1996-1998 Clinical Fellow, Dermatology Branch, NIH, Bethesda, MD
1999-2005 Assistant Professor of Dermatology, Assistant Professor of Anatomy Physiology and Genetics (secondary), Uniformed Services University of the Health Sciences
2005-2012 Associate Professor of Dermatology, (tenured 2005) Associate Professor of Anatomy Physiology and Genetics (secondary), Associate Professor of Molecular and Cell Biology (secondary), Uniformed Services University of the Health Sciences
2012-present Professor of Dermatology Professor of Anatomy Physiology and Genetics (secondary), Professor of Molecular and Cell Biology (secondary), Uniformed Services University of the Health Sciences
2014-present Chair of Dermatology Uniformed Services University of the Health Sciences, Bethesda, MD
1994-1998 United States Public Health Service, Research Officer Group, 0-3 (LT) Sr. Assistant Surgeon, promoted to Permanent Grade: 0-4 (LT Commander) Surgeon, Bethesda, MD
2009 James Leonard Award for Excellence in Clinical Research, USUHS
2012 Member of research team that received a National Human Genome Research Institute GREAT Award, for “Discovery of the cause of Proteus syndrome”
2013 Member, American Dermatological Association
2013 Member of research team that received a National Human Genome Research Institute GREAT Award, for “Defining a new class of human disease caused by somatic mutations in the PI3K-AKT1 pathway”
2016 Member of research team to receive a NHLBI Orloff Science Award for studies of circulating tumor cells in patients with LAM and TSC
Klover PJ, Thangapazham RL, Kato J, Wang JA, Anderson SA, Hoffmann V, Steagall WK, Li S, McCart E, Nathan N, Bernstock JD, Wilkerson MD, Dalgard CL, Moss J, Darling TN. Tsc2 disruption in mesenchymal progenitors results in tumors with vascular anomalies overexpressing Lgals3. Elife. 2017;6. pii: e23202. PMID: 28695825
Bongiorno MA, Nathan N, Oyerinde O, Wang JA, Lee CR, Brown GT, Moss J, Darling TN. Clinical Characteristics of Connective Tissue Nevi in Tuberous Sclerosis Complex With Special Emphasis on Shagreen Patches. JAMA Dermatol. 2017;153(7):660-665. PMID:
Nathan N, Burke K, Moss J, Darling TN. A diagnostic and management algorithm for individuals with an isolated skin finding suggestive of tuberous sclerosis complex. Br J Dermatol. 2017;176(1):220-223. PMID: 27167640
Nathan N, Tyburczy ME, Hamieh L, Wang JA, Brown GT, Richard Lee CC, Kwiatkowski DJ, Moss J, Darling TN. Nipple Angiofibromas with Loss of TSC2 Are Associated with Tuberous Sclerosis Complex. J Invest Dermatol. 2016;136(2):535-8. PMID: 26824744
Nathan N, Burke K, Trickett C, Moss J, Darling TN. The Adult Phenotype of Tuberous Sclerosis Complex in Men. Acta Derm Venereol. 2016;96(2):278-80. PMID: 26258325
Nathan N, Wang JA, Li S, Cowen EW, Haughey M, Moss J, Darling TN. Improvement of tuberous sclerosis complex (TSC) skin tumors during long-term treatment with oral sirolimus. J Am Acad Dermatol. 2015;73:802-8. PMID: 26365597
Teng JM, Cowen EW, Wataya-Kaneda M, Gosnell ES, Witman PM, Hebert AA, Mlynarczyk G, Soltani K, Darling TN. Dermatologic and dental aspects of the 2012 international tuberous sclerosis complex consensus statements. JAMA Dermatol. 2014;150:1095-101. PMID: 25029267
Thangapazham RL, Klover P, Li S, Wang JA, Sperling L, Darling TN. A model system to analyze the ability of human keratinocytes to form hair follicles. Exp Dermatol. 2014;23:443-6. PMID: 24758480
Tyburczy ME, Wang JA, Li S, Thangapazham R, Chekaluk Y, Moss J, Kwiatkowski DJ, Darling TN. Sun exposure causes somatic second-hit mutations and angiofibroma development in tuberous sclerosis complex. Hum Mol Genet. 2014;23:2023-9. PMID: 24271014
1995 Ph.D. in Pysiology, University College London, United Kingdom
1990 BSc with honours in Biological Sciences, Birmingham, United Kingdom
My research interest is in neurogenesis with a particular focus on the transcriptional control of neuronal specification and differentiation. My early training investigated cerebellar development in spontaneous mutant mice models using classical histochemistry and electron microscopy techniques. As a postdoctoral researcher and later a Research Assistant Professor, I gained considerable experience in the creation and application of transgenic and targeted mutant mouse models in neurodevelopment research at The Rockefeller University. More recently my work has focused on using human induced pluripotent stem cells to model physiological and pathophysiological mechanisms of neuronal network connectivity in vitro. I am particularly interested in the role epigenetic factors play in neurogenesis and I have published several peer-reviewed publications on this topic in the last few years.
B.S. Stevens Institute of Technology, Hoboken, NJ Major: Chemical Biology; Minor: History 1989 – 1993
M.S. University of Maryland, Baltimore, MD Major: Physiology 1994 – 1996
Ph.D. University of Maryland, Baltimore, MD Major: Physiology 1996 – 2001
Mentor: Paul A. Welling, M.D.
Postdoctoral Washington University School of Medicine, St. Louis, MO 2001 - 2004
Mentor: Colin G. Nichols, Ph.D.
Geiger RM, MG Klein, N Fatima, RE Goldstein, MJ Krantz, MC Haigney, and TP Flagg. Rapid Assessment of Proarrhythmic Potential Using Human iPSC-Derived Cardiomyocytes. JACC Clin Electrophysiol, in press, 2020.
Khayrullina G, Moritz KE, Schooley JF, Fatima N, Viollet C, McCormack NM, Smyth JT, Doughty ML, Dalgard CL, Flagg TP, Burnett BG. SMN-deficiency disrupts SERCA2 expression and intracellular Ca2+ signaling in cardiomyocytes from SMA mice and patient-derived iPSCs. Skelet Muscle.10:16, 2020.
Goldstein RE, Klein MG, Ouimet SP, Shou M, Hood MN, Flagg TP, Haigney MC. Hemodynamic Effects of Late Sodium Current Inhibitors in a Swine Model of Heart Failure. J Card Fail. 25:828-836, 2019.
Flagg, TP, SW Rothwell, and BE Neubauer. Avoiding the chopping block in curricular reform - re-imagining physiology laboratories in the era of integrated medical curricula. Adv Physiol Educ, 41: 279-285, 2017.
Klein, MG, M Shou, J Stohlman, M Haigney, RR Tidwell, TP Flagg, RE Goldstein, MC Haigney. Role of IK1 Suppression on Terminal Action Potential Repolarization in the Failing Heart. Heart Rhythm, 14:1217-1223, 2017.
Klein, MG, MC Haigney, PS Mehler, N Fatima, TP Flagg, and MJ Krantz. Potent Inhibition of hERG Channels by the Over-The Counter Anti-Diarrheal Agent Loperamide, JACC Clin Electrophysiol, 251, 2016.
Fatima, N, DC Cohen, JF Schooley, Jr., MC Haigney, WC Claycomb, CL Dalgard, RT Cox, SE Bates, and TP Flagg. Histone deacetylase inhibitors modulate KATP subunit transcription in HL-1 cardiomyocytes through effects on cholesterol. Frontiers Pharmacol, 6:168, 2015.
Schooley, Jr., JF, AMA Namboodiri, RT Cox, R Bunger, and TP Flagg. Acetate Transiently Inhibits Myocardial Contraction by Increasing Mitochondrial Calcium Uptake. BMC Physiol,14:12, 2014.
Fatima, N., JF Schooley, Jr., WC Claycomb, and TP Flagg. Promoter DNA methylation regulates murine SUR1 (Abcc8) and SUR2 (Abcc9) expression in HL-1 cardiomyocytes. PlosOne, 7: e41533, 2012.
University of Wroclaw, Department of Experimental Physics, Wroclaw, Poland. M.Sc.
Academy of Medicine, Wroclaw, Poland, Ph.D.
Laboratory of Neurosciences, NIA, NIH, Postdoctoral
1986-1988 Visiting Fellow, research in electrophysiology and teaching- lecturer graduate students Course on Cellular Biophysics and Physiology, Biophysics Laboratory, International School for Advanced Studies (SISSA), Trieste, Italy.
1987 Research Fellow, postdoctoral studies in electrophysiology under supervision of Dr. Franco Conti, Institute of Cybernetics and Biophysics, CNR, Genova- Camogli, Italy.
1990-1994 Visiting Associate, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD.
1994-1999 Chief, Unit on Cell Pathophysiology, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD.
2000-2004 Assistant Professor Department of Anatomy, Physiology and Genetics, USUHS, School of Medicine, Bethesda MD.
2004-2012 Associate Professor Department of Anatomy, Physiology and Genetics, USUHS, School of Medicine, Bethesda MD.
2012-present Professor, Department of Anatomy, Physiology and Genetics (Primary appointment), Neuroscience and Molecular and Cell Biology Program (Secondary appointments), USUHS, School of Medicine, Bethesda MD.
L. Chakrabarti, T.K. Best, N.P. Cramer, R.S. Carney, J.T. Isaac, Z. Galdzicki, T.F. Haydar, Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome. Nat Neurosci. 2010, 13(8):927-34.
J. Keck-Wherley, D. Grover, S. Bhattacharyya, X. Xu, D. Holman, E.D. Lombardini, R. Verma, R. Biswas, Z. Galdzicki, Abnormal microRNA expression in Ts65Dn hippocampus and whole blood: contribution to Down syndrome phenotypes, Developmental Neuroscience 2011, 33(5):451-67.
N. Cramer, Z Galdzicki From abnormal hippocampal synaptic plasticity in Down syndrome mouse models to cognitive disability in Down syndrome. Neural Plast. 2012:101542. doi: 10.1155/2012/101542.
JA Rusiecki, C Byrne, Z Galdzicki, V Srikantan, L Chen, M Poulin, L Yan, A Baccarelli PTSD and DNA methylation in select immune function gene promoter regions: a repeated measures case-control study of U.S. military service members, Front Psychiatry. 2013 Jun 24;4:56.
Olmos-Serrano JL, Kang HJ, Tyler WA, Silbereis JC, Cheng F, Zhu Y, Pletikos M, Jankovic-Rapan L, Cramer NP, Galdzicki Z, Goodliffe J, Peters A, Sethares C, Delalle I, Golden JA, Haydar TF, Sestan N., Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination, Neuron. 2016 Mar 16;89(6):1208-22.
Logue OC, Cramer NP, Xu X, Perl DP, Galdzicki Z., Alterations of functional properties of hippocampal networks following repetitive closed-head injury. Exp Neurol. 2016 Mar;277:227-43.
Cramer NP, Xu X, F Haydar T, Galdzicki Z., Altered intrinsic and network properties of neocortical neurons in the Ts65Dn mouse model of Down syndrome. Physiol Rep. 2015 Dec;3(12).
Cramer NP, Xu X, Christensen C, Bierman A, Tankersley CG, Galdzicki Z., Strain variation in the adaptation of C57Bl6 and BALBc mice to chronic hypobaric hypoxia. Physiol Behav. 2015, 143:158-65.
C. Harashima, D.M. Jacobowitz, J. Witta, R.C. Borke, T.K. Best, R.J. Siarey, Z. Galdzicki, Abnormal expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in hippocampus, frontal cortex, and substantia nigra of Ts65Dn mouse: a model of DS, J of Comp.Neurobiology 2006 494(5):815-833.
R.J. Siarey, A. Kline-Burgess, M. Cho, A. Balbo, T.K. Best, C. Harashima, E. Klann, Z. Galdzicki Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in the Ts65Dn mouse model of Down Syndrome, J Neurochem. 2006 98(4):1266-1277.
T.K. Best, R.J. Siarey, Z. Galdzicki Ts65Dn, a mouse model of Down syndrome, exhibits increased GABAB induced potassium current. J Neurophysiol. 2007 97: 892-900.
Olson LE, Roper RJ, Sengstaken CL, Peterson EA, Aquino V, Galdzicki Z, Siarey R, Pletnikov M, Moran TH, Reeves RH. Trisomy for the Down syndrome 'critical region' is necessary but not sufficient for brain phenotypes of trisomic mice. Hum Mol Genet., 2007, 16: 774-782.
L. Chakrabarti, Z. Galdzicki, T.F. Haydar Defects in embryonic neurogenesis and initial synapse formation in the forebrain of the Ts65Dn mouse model of Down syndrome. J Neurosci. 2007 27:11483-11495.
K-H. Baek, A. Zaslavsky , R.C. Lynch, C. Britt, Y. Okada, R.J. Siarey, M.W. Lensch, I.H. Park, S.S. Yoon, T. Minami, J.R. Korenberg, R. Reeves, J. Folkman, W.C. Aird, Z. Galdzicki, S. Ryeom, Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. Nature 2009; 459:1126-30.
1961 1967 The School of Basic Medical Sciences, Beijing Medical University (Now: Peking University Health Science Center); Beijing, China
1978 1981 Graduate study in Department of Biophysics, Beijing Medical University. (Now: Peking University Health Science Center); Beijing, China
1982 1983 National NMR Professional Training Program Sponsored by The Ministry of Education of China.
1961 1967 M.D. (Equivalent) The School of Basic Medical Sciences, Beijing Medical University (Now: Peking University Health Science Center); Beijing, China
1978 1981 M.S. (Biophysics) Graduate study in Department of Biophysics, Beijing Medical University (Now: Peking University Health Science Center); Beijing, China
1982 1983 National NMR Professional Training Program Sponsored by The Ministry of Education of China
1985 1986 Research Associate in Dr. C. S. Johnson's Lab. of the Dept of Chemistry and Dr. D. A. Gabriel's Lab. of the Medical School in the University of North Carolina at
Chapel Hill, U. S. A. Studied protein molecular diffusion coefficient by Laser Holographic Relaxation Spectroscopy and cell electrophoresis by Laser Doppler Light
1986 1988 Research Associate in Dr. Valerie W. Hu’s Lab, Dept. of Biochemistry, USUHS, Bethesda, Maryland. U.S.A. Studied the interaction of toxin (diphtheria) protein
1988 1988 Postdoctor in Dr. M. D. Rollag's Lab and Dr. M. R. Adelman's Lab. of the Dept. of Anatomy and Cell Biology, USUHS. Set up the microinjection apparatus and
studied the pigment movement of cultured amphibian melanophores by microinjection method.
1988 1991 Research Associate in Dr. K. V. Holmes' Lab. Dept. of Pathology, USUHS.
Identification and characterization of the receptor for Mouse Hepatitis Virus (MHV; a murine Coronavirus) as a member of the Carcinoembryonic antigen Family of
1991- 1992 Research Associate in Dr. R. M. Friedman's Lab. Dept. of Pathology, USUHS.
Studied tumor suppressor gene (rrg: ras recession gene), the gene product (lysyl oxidase) and its role in reversion process of cell transformation.
1968 1978 Physician of Occupational Diseases and Doctor of Radiation Department. Hospital of First Coal Mining Engineering Company of Gan su Province, China.
1981 1985 Lecturer of Biophysics, Dept. of Biophysics. One of the originators of the Central laboratory with Mass spectrometer, NMR, Electron microscopes and other large
equipment in Beijing Medical University, China.
1992- 1995 Senior Research Associate in Dept. of R. & D. Univax Biologics Inc.Purification and characterization of recombinant protein and polysaccharide for vaccine
development. Developed the assay methods (Enzyme assay, uronic acid assay, O-acetylation assay, nonionic detergent assay.)
1995 1995 Research scientist in Dr. M. D. Rollag's Lab. of the Dept. of Anatomy, Physiology and Genetics, USUHS. Identifying and characterization of an opsin (melanopsin) in t
he cultured amphibian melanophores.
1995- 2003 Research Assistant professor in Dept. of Anatomy, physiology and Genetics, USUHS. Cloning and expression of Melanopsin gene of amphibian, chicken, mouse and
2003- 2017 Research Assistant professor in Dept. of Anatomy, physiology and Genetics, USUHS. Proteomic research focusing on the mass spectrometry (MS) running High
performance liquid chromatography (HPLC)–MS. Techniques’ development and maintenance of MS.
1968 1978 Physician of Occupational Diseases and Doctor of Radiation Department. Hospital of First Coal Mining Engineering Company of Gan su Province, China.
1981 1985 Lecturer of Biophysics, Dept. of Biophysics. One of the originators of the Central laboratory with Mass spectrometer, NMR, Electron microscopes and other large equipment in Beijing Medical University, China
1992- 1995 Senior Research Associate in Dept. of R. & D. Univax Biologics Inc. Purification and characterization of recombinant protein and polysaccharide for vaccine development. Developed the assay methods (Enzyme assay, uronic acid assay, O-acetylation assay, nonionic detergent assay.)
1995- 2003 Research Assistant professor in Dept. of Anatomy, physiology and Genetics, USUHS. Cloning and expression of Melanopsin gene of amphibian, chicken, mouse and human.
2003- 2017 Research Assistant professor in Dept. of Anatomy, physiology and Genetics, USUHS. Proteomic research focusing on the mass spectrometry (MS) running High performance liquid chromatography (HPLC)–MS. Techniques’ development and maintenance of MS.
Guisen Jiang: Shield Ruler and Methods of Using the Same. U.S. Patent Application Number 61/902,893 on 11/12/2013 at the United States Patent and Trademark Office.
Jiang Gui sen and Lin Ke chun: Fluidity Changes of Membrane Lipid Regions in Leukemic Lymphocytes. Acta Biochimica et Biophysica Sinica, Vol. 16, No. 6, P. 521-527, 1984 (with English Summary)
K. C. Lin and G. S. Jiang: 31P NMR Study of the Interaction Between Surfactants and Liposomes. Acta Biophysica Sinica, Vol. 2, No. 3, P. 233, 1986. (with English Summary)
Jiang Gui sen and Valerie W. Hu: Characterization of Diphtheria Toxin mediated Marker Release from Asolectin Vesicles. Biophysical Journal, Vol. 53, No. 2, part 2, P. 314a. 1988.
Gui sen Jiang, Rikki Solow, and Valerie W. Hu: Characterization of Diphtheria Toxin Induced Lesion in Liposomal Membranes: An Evaluation of the Relationship Between Toxin Insertion and "Channel" Formation. J. Biol. Chem., Vol. 264, No. 23, P. 13424, 1989.
Guisen Jiang, Rikki Solow, and Valerie W. Hu: Fragment A of Diphtheria Toxin Causes pH-Dependent Lesions in Model Membranes. J. Biol. Chem., Vol.264, No. 29, P. 17170, 1989.
Richard K. Williams, Guisen Jiang, Stuart W. Snyder, Mark F. Frana and Kathryn V. Holmes: Purification of the 110K Glycoprotein Receptor for Mouse Hepatitis Virus ( MHV )-A59 from Mouse Liver and Identification of a Nonfunctional, Homologous Protein in MHV-Resistant SJL/J Mice. J. Virol., Vol. 64, No. 8, P. 3817-3823, 1990.
Richard K. Williams, Guisen Jiang, and Kathryn V. Holmes: Receptor for mouse hepatitis Virus is a member of the Carcinoembryonic antigen Family of glycoproteins. Proc. Natl. Acad. Sci. USA. Vol. 88, p. 5533-5536, 1991.
Ignacio Provencio, Guisen Jiang, Willem J. De Grip, William Par Hayes, and Mark D. Rollag: Melanopsin: An opsin in melanophores, brain, and eye Proc. Natl. Acad. Sci. USA. Vol. 95, p. 340-345, 1998
Ignacio Provencio, Ignacio R. Rodriguez, Guisen Jiang, William Par Hayes, Ernesto F. Moreira, and Mark D. Rollag: A Novel Human Opsin in the Inner Retina The Journal of Neuroscience, January 15, 2000, 20(2):600–605
Juang YT, Wang Y, Jiang G, Peng HB, Ergin S, Finnell M, Magilavy A, Kyttaris VC, Tsokos GC. PP2A Dephosphorylates Elf-1 And Determines The Expression Of CD3zeta And FcRgamma In Human Systemic Lupus Erythematosus T Cells. J Immunol. 2008 Sep 1;181(5):3658-64
Flexnor Award for Outstanding Research, Institute for Neurological Sciences Philadelphia, PA, 1981.
Recipient of Cajal Club, Cortical Explorer Award for Excellence in Research, 1992.
Simpson Award, given by iiFAR (Incurably ill for Animal Research), 1992.
Distinguished Service Medal, awarded by the Department of Defense for service to USUHS, 1998.
Simpson Award, given by iiFAR (Incurably ill for Animal Research), 1992.
Henry Wu Award for Excellence in Research, USUHS, Bethesda MD, 2011.
Outstanding Service Medal, awarded by the Department of Defense for service to USUHS & CNRM, Bethesda MD 2012.
Award for Education in Neuroscience, awarded by the Society for Neuroscience, 2012.
Chair, USCRC (IBRO North American Regional Committee), 2013- present.
Organizer Teaching Tools Workshops in Africa, 2008-2017
Schwerin SC, Hutchinson EB, Radomski KL, Ngalula KP, Pierpaoli CM, Juliano SL. Establishing the ferret as a gyrencephalic animal model of traumatic brain injury: Optimization of controlled cortical impact procedures. J Neurosci Methods. 2017 May 9. pii: S0165-0270(17)30129-2. doi: 10.1016/j.jneumeth.2017.05.010. [Epub ahead of print].
Elizabeth B. Hutchinson, Alexandru V. Avram, M. Okan Irfanoglu, C. Guan Koay, Alan S. Barnett, Miki E. Komlosh, Evren Ozarslan, Susan C. Schwerin, Sharon L. Juliano and Carlo M. Pierpaoli. Cross-model analysis of noise, experimental design and model parameters for diffusion MRI in the fixed mouse brain. Magnetic Resonance in Medicine, in press.
Trentini, J.F., O’Neill, J.T., Juliano, S.L., Prenatal CO exposure results in abnormal migration of interneurons into the cerebral cortex, Neurotoxicology. Mar;53:31-44. doi: 10.1016/j.neuro.2015.11.002. Epub 2015 Nov ‘’’’;12. 2016.
Poluch, S. and Juliano, S.L. Fine tuning of neurogenesis is essential for the evolutionary expansion of the cerebral cortex, Cerebral Cortex, 25: 346-64, 2015.
Abbah, J., Braga M. F., and Juliano, S. L. Targeted disruption of layer 4 during development increases GABAA receptor neurotransmission in the neocortex, J Neurophysiol, Jan;111(2):323-35, 2014.
Abbah, J. and Juliano, S.L. Altered kinetic behavior underlies redistribution of interneurons in a model of cortical dysplasia: the influence of elevated GABAA activity, Cerebral Cortex, 24: 2297-308, 2014.
Poluch, S. and Juliano, S.L., Distinct populations of radial glial cells respond differently to reelin and neuregulin1 in a ferret model of cortical dysplasia, PLoSOne. Oct 28;5(10):e13709, 2010.
Corbin, J., Gaiano, N., Juliano, S.L., Poluch, S., Stancik, E., Haydar, T. Regulation of neural progenitor cell development in the nervous system. J. Neurochem. 106:2272-87, 2008.
Poluch, S., Jablonska, B., and Juliano, S.L. Alteration of tangential migration and GABA phenotype in a ferret model of cortical dysplasia. Cerebral Cortex, Epub 2007 Apr 18; 18:78-92, 2008.
Poluch, S. and Juliano, S.L. A normal radial glial scaffold is necessary for tangential migration during neocortical development. Glia, 55: 822-830, 2007.
Doctor of Medicine and General Surgery, University of Chile. Santiago Chile, 1994
Licentiate in Medicine, University of Chile. Santiago Chile 1992
Leighton X, Eidelman O, Jozwik C, Pollard HB, Srivastava M. ANXA7-GTPase as Tumor Suppressor: Mechanisms and Therapeutic Opportunities. Methods Mol Biol. 2017; 1513:23-35.
Srivastava A, Leighton X, Eidelman O, Starr J, Jozwik C, Srivastava M, Pollard H.B. and Singh VK. Personalized radioproteomics: Identification of a protein biomarker signature for preemptive rescue by tocopherol succinate in CD34+ irradiated progenitor cells isolated from a healthy control donor. Journal of Proteomics & Bioinformatics. 8:2, 23-30,
Diverse Effects of ANXA7 and p53 on LNCap Prostate Cancer Cells Are associated with Regulation of SGK1 Transcription and Phosphorylation of the SGK1 Target FOXO3A. Meera Srivastava, Ximena Leighton, Joshua Star Ofer #Eidelman, and Harvey Pollard. BioMed Research International, Volume 2014, (2014).
Mears D, Zimliki CL, Atwater I, Rojas E, Glassman M, Leighton X, Pollard HB, Srivastava The Anx7 (+/-) Knockout Mutation Alters Electrical and Secretory Responses to Ca- Mobilizing Agents in Pancreatic β-cells. Cell Physiol. Biochem.2012; 29 (5-6): 697-704.
Torosyan Y, Dobi A, Glasman M, Mezhevaya K, Naga S, Huang W, Paweletz C, Leighton X, Pollard HB, Srivastava M. Role of multi-hnRNP nuclear complex in regulation of tumor suppressor ANXA7 in prostate cancer cells. Oncogene 2010; 29 (17). 2457-66
Torosyan Y, Simakova O, Naga S, Mezhevaya K, Leighton X, Diaz J, Huang W, Pollard H, Srivastava M. Annexin-A7 protects normal prostate cells and induces distinct patterns of RB-associated cytotoxicity in androgen-sensitive and -resistant prostate cancer cells. Int J Cancer 2009; 125(11):2528-39.
Leighton, X., Srikantan, V., Sukumar, S., Pollard, H.B. and Srivastava, M. Significant allelic loss of ANX7 region (10q21) in hormone receptor negative breast carcinomas, 2004.Cancer Letts 210 (2004) 239-244.
Srivastava, M., Glasman, M., Leighton, X., Miller, G., Montagna, C., Reid, T., and Pollard, H.B.Genomic instability and gene expression profile in cancer prone Anx7 (+/-) knockout mouse and cell line models. Proc Natl Acad Sci USA. 2003; 100, 14287-14292.
Srivastava, M., Montagna, C., Leighton, X., Glasman, M., Naga, S., Eidelman, O., Reid, T. and Pollard, H.B., Haploinsufficiency of ANX 7 tumor suppressor gene and consequent genomic instability promotes tumorgenesis in the ANX7 (+/-) mouse.Proc. Natl. Acad. Sci. 2003, 100, 14287-14292.
Faculty of Physics of Shevchenko State University in Kyiv, Ukraine. Ph.D. in biophysics and electrophysiology from Bogomoletz Institute of Physiology, Kyiv, Ukraine.
NAME: Volodymyr Pidoplichko
1965 - 1970 Kiev State University (Faculty of Physics, B.S. in Molecular Physics)
1974 -1975 Ph.D. ( “Candidate of Biol. Sciences” ) Bogomoletz Institute of Physiology, Ukr.
Acad. Sci., Kyiv, Ukraine
1975 - 1987 “Doctor of Biol. Sciences“ , senior sci. degree
1970 - 1972 Research Fellow with Dr. P.G.Kostyuk,
Bogomoletz Institute of Physiology, Kiev, Ukraine
1972 - 1974 Lieutenant-Engineer, radar specialist, Soviet Air Force
1974 - 1980 Junior Research Scientist,
Dr. P.G.Kostyuk, Chairman,
Bogomoletz Institute of Physiology, Kiev, Ukraine
1980 - 1988 Senior Research Scientist, Bogomoletz Institute of Physiology, Kiev, Ukraine
1988 - 1989 Senior Research Scientist,
Dr. Yu. Yu. Gleba, Dept. Head,
Div. of Cell Biology and Engineering, Institute of Botany, Kiev, Uktaine
1989 - 1990 Head of the Laboratory of Molecular Physiology,
Dr. Yu. Yu. Gleba, Chairman,
Institute of Cell Biology and Engineering, Kiev, Ukraine
1991 - 1992 Head of the Department of Membranology and Phytochemistry,
Dr. K.M.Sytnik, Chairman,
Institute of Botany, Kiev, Ukraine
1992 - 1995 Research Scientist,
Dr. K. G. Reymann, Dept. Head,
Institute for Neurobiology, Magdeburg, Germany
1995 - 1996 Head of the Dep. of Membranology and Phytochemistry,
Dr. K.M.Sytnik, Chairman,
Institute of Botany, Kiev, Ukraine
1996 - 2006 Research Associate/Instructor,
Dr. John A. Dani,
Div. of Neuroscience, Baylor College of Medicine, Houston, USA
2007-2014 Research Associate
Prof. Dr. Maria F. Braga,
Dep. of Anatomy, Physiology and Genetics, Uniformed Services
University of the Health Sciences, Bethesda, USA
2014-present Research Associate Professor
Prof. Dr. Maria F. Braga,
Dep. of Anatomy, Physiology and Genetics, Uniformed Services
University of the Health Sciences, Bethesda, USA
1983 Recipient State prize USSR Council of Ministers
Pidoplichko V.I. & Verkhratsky A.N. (1984) Possible existence of tetrodotoxin-sensitive voltage-dependent chloride conductance in the membrane of perfused cardiomyocytes. Doklady Akad. Nauk SSSR, Moscow, v.279, pp.1012-1015 (in Russian)
Wilsch V.W., Pidoplichko V.I., Opitz T., Shinozaki H. & Reymann K.G. (1994) Metabotropic glutamate receptor agonist DCG-IV as NMDA receptor agonist in immature rat hippocampal neurons. Eur. J. Pharmacol. v.262, pp.287-291
Pidoplichko V.I., Wilsch V.W. & Reymann K.G. (1996) Fast desensitizing kainate-gated current resolved in whole-cell experiments on isolated rat hippocampal neurons. Eur. J. Pharmacol., v. 303, pp.145-149
Pidoplichko V.I. (1996) Dependence of solution exchange time on cell or patch linear dimensions in concentration jump experiments using patch-clamped sensory neurons. Pflugers Arch. - Eur. J. Physiol. v. 432, pp. 1074-1079
Pidoplichko VI, Dani JA. (2005) Applying small quantities of multiple compounds to defined locations of in vitro brain slices. J Neurosci Methods. v.142(1), pp.55-66.
Pidoplichko VI, Dani JA. (2006) Acid-sensitive ionic channels in midbrain dopamine neurons are sensitive to ammonium, which may contribute to hyperammonemia damage. Proc Natl Acad Sci U S A. v.103(30) pp.11376-80.
Kostyuk P.G., Krishtal O.A. & Pidoplichko V.I. (1972) Potential-dependent membrane current during the active transport of ions in snail neurones. J.Physiol., London, v.226, pp.373-392
Krishtal O.A. & Pidoplichko V.I. (1975) Intracellular perfusion of snail giant neurons. Neirofiziologiya, Kiev, v.7, pp.327-329 (in Russian)
Kostyuk P.G., Krishtal O.A. & Pidoplichko V.I. (1975) Effect of internal fluoride and phosphate on membrane currents during intracellular dialysis of nerve cells. Nature, London, v.257, pp.691-693
Kostyuk P.G., Krishtal O.A. & Pidoplichko V.I. (1977) Asymmetrical displacement currents in nerve cell membrane and effect of internal fluoride. Nature, London, v.267, pp.70-72
Krishtal O.A. & Pidoplichko V.I. (1980) A receptor for protons in the nerve cell membrane. Neuroscience, v.5, pp.2325-2327
Kostyuk P.G., Krishtal O.A. & Pidoplichko V.I. (1981) Calcium inward current and related charge movements in the membrane of snail neurones. J.Physiol., London, v.310, pp.403-421
Krishtal O.A., Marchenko S.M. & Pidoplichko V.I. (1983) Receptor for ATP in the membrane of mammalian sensory neurones. Neuroscience Letters, v.35, pp.41-45
Pidoplichko V.I. (1992) Ammonia and proton-gated channel populations in trigeminal ganglion neurons. Gen Physiol. Biophys., v.11, pp.39-48
Pidoplichko V.I. , DeBiasi M., Williams J.T. & Dani J.A.(1997) Nicotine activates and desensitizes midbrain dopamine neurons. Nature, v.290, pp. 401-404
Pidoplichko V.I., Aroniadou-Anderjaska V, Prager E.M., Figueiredo T.H., Almeida-Suhett C.P., Miller S.L. & Braga M.F. (2014) ASIC1a activation enhances inhibition in the Basolateral Amygdala and reduces anxiety. J.Neuroscience, v.34(9), pp.3130-3141
INSTITUTION AND LOCATION DEGREE YEAR(s) FIELD OF STUDY
Rice University, Houston, TX B.A. 1964 Biology
University of Chicago, Chicago, IL M.D. 1969 Medicine
University of Chicago, Chicago, IL Ph.D. 1973 Biochemistry
Dr. Pollard received his undergraduate degree from Rice University, and his MD and PhD (in Biochemistry) degrees from the University of Chicago. Following postdoctoral training at the NIH and at Oxford University, Dr. Pollard returned to the NIH in the U.S. Public Health Service (USPHS), eventually becoming intramural Chief of the Laboratory of Pathology, and then Chief of the Laboratory of Cell Biology and Genetics, NIDDK. Dr. Pollard subsequently moved across Wisconsin Avenue to become Chair of the Department of Anatomy, Physiology and Genetics, in the Uniformed Services University School of Medicine, Bethesda, MD. Dr. Pollard’s principal hypothesis-driven research focus has been on proinflammatory mechanisms. Dr. Pollard is the Founding Director of the Collaborative Health Initiative Research Program (CHIRP), a whole genome sequencing (WGS) program of investigation, jointly sponsored by NHLBI and the Department of Defense. In addition, Dr. Pollard is also Founding Director of The American Genome Center (TAGC), a Department of Defense entity that is one of only four academic Genome Centers in the United States.The goals of CHIRP and the TAGC are to develop “precision medicine” as an aid to diagnosis and treatment of disorders of common interest in both civilian and military disease cohorts. Dr. Pollard has received the NIH Inventor’s Award, and has authored nearly 350 peer reviewed scientific publications and numerous invited chapters.
Laboratory Chief, Laboratory of Cell Biology and Genetics,NIADDK,
Professor and Chair of the Department of Anatomy and Cell Biology, USUSOM, USUHS
Professor and Chair of the Department of Anatomy, Physiology & Genetics, USUSOM, USUHS
Director of the Collaborative Health Initiative Research Program (CHIRP) and The American Genome Center (TAGC)
Dalgard C, Eidelman O, Jozwik C, Olsen CH, Srivastava M, Biswas R, e EudyY,.Rothwell SW, Mueller GP, Yuan P, Drevets WC, Manji HK, Vythlingam M, Charney DS. Neumeister A, Ursano RJ, Jacobowitz DM, Pollard HB, and Bonne O., The MCP-4/MCP-1 Ratio in Plasma is a Candidate Circadian Biomarker for Chronic Post-Traumatic Stress Disorder. Translational Psychiatry, 7(2):e1025 doi:10.1038/tp2016.285, 2017, 2016.
Dalgard CL, Polston KF, Sukumar G, Mallon CT, Wilkerson MD, Pollard HB. MicroRNA Expression Profiling of the Armed Forces Health Surveillance Branch Cohort for Identification of "Enviro-miRs" Associated With Deployment-Based Environmental Exposure. J Occup Environ Med. 2016 Aug;58(8 Suppl 1):S97-S103. doi: 10.1097/ JOM.0000000000000764., 2016
. Pollard HB, Shivakumar C, Starr J, Eidelman O, Jacobowitz DM, Dalgard CL, Srivastava M, Wilkerson MD, Stein MB, Ursano RJ. "Soldier's Heart": A Genetic Basis for Elevated Cardiovascular Disease Risk Associated with Post-traumatic Stress Disorder. Front Mol Neurosci. 2016 Sep 23;9:87, 2016
Wang H, Cebutaru L, Yang QF, Jozwik C, Pollard BS, Pollard HB and Guggino WB. CFTR controls the activity of the NFκB by enhancing the degradation of TRADD. Cell Physiol.Biochem. , 40(5): 1063-1078, 2016. 2016.
. Singh VK, Newman VL, Romaine PL, Hauer-Jensen M, Pollard HB. Use of biomarkers for assessing radiation injury and efficacy of countermeasures.
. Mears D, Pollard HB. Network science and the human brain: Using graph theory to understand the brain and one of its hubs, the amygdala, in health and disease.
Veit G, Avramescu RG, Chiang AN, Houck SA, Cai Z, Peters KW, Hong JS, Pollard HB, Guggino WB, Balch WE, Skach WR, Cutting GR, Frizzell RA, Sheppard DN, Cyr DM, Sorscher EJ, Brodsky JL, Lukacs GL. From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations. Mol Biol Cell. 2016 Feb 1;27(3):424-33. doi: 10.1091/mbc.E14-04-0935.PMID: 26823392
. Caohuy H, Yang Q, Eudy Y, Ha TA, Xu AE, Glover M, Frizzell RA, Jozwik C, Pollard HB. Activation of 3-phosphoinositide-dependent kinase 1 (PDK1) and serum- and glucocorticoid-induced protein kinase 1 (SGK1) by short-chain sphingolipid C4-ceramide rescues the trafficking defect of ΔF508-cystic fibrosis transmembrane conductance regulator (ΔF508-CFTR). J Biol Chem. 2014 Dec 26;289(52):35953-35968. doi: 10.1074/jbc.M114.598649. Epub 2014 Nov 10.
. Kumar P, Bhattacharuyya S, Peters KW, Glover ML, Sen A, Cox RT, Bhattacharyya A, Kundu S, Caohuy H, Frizzell RA, Pollard HB and Biswas R. Functional rescue of [ΔF508]CFTR in native cystic fibrosis cells by miR-16. Gene Ther. 22(11): 908-916, 2015
Dalgard CL, Jacobowitz DM, Singh V, Saleem KS, Ursano RJ, Starr JM, and 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 Research 1600:42-58, 2015.
2002 Ph.D. in Neuroscience, University of Sciences, Montpellier, France.
1999 Diploma of Advanced Studies in Cellular and Molecular Endocrinology, University of Sciences, Montpellier, France.
1997 Master in Cellular Biology and Physiology, University of Sciences, Reims, France.
1996 Bachelor of Science in Cellular Biology and Physiology, University of Sciences, Reims, France.
Poluch S & Juliano S. 2015. Fine-tuning of neurogenesis is essential for the evolutionary expansion of the cerebral cortex. Cerebral Cortex, 25:346-364. Cover featured article.
Trousse F, Poluch S, Pierani A, Dutrieux A, Bock H, Nagasawa T, Verdier M & Rossel M. 2015. The CXCR7 receptor controls positioning of a subpopulation of Cajal-Retzius cells. Cerebral Cortex, 10:3446- 3357.
Poluch S & Juliano S. 2010. Populations of radial glial cells respond differently to reelin and neuregulin1 in a ferret model of cortical dysplasia. PLOS One. 10:e13709.
Poluch S, Jablonska B & Juliano S. 2008. Alteration of interneuron migration in a ferret model of cortical dysplasia. Cerebral Cortex, 18:78-92.
Poluch S & Juliano S. 2007. A normal radial glial scaffold is necessary for tangential migration during neocortical development. Glia, 55:822-830.
Poluch S & König N. 2002. AMPA receptor activation induces GABA release from neurons migrating tangentially in the intermediate zone of embryonic rat neocortex. Eur J Neurosci, 16:350-354.
2009-2013 Postdoctoral Fellowship in Neuroscience, Uniformed Services University, Bethesda, MD
2006-2009 Postdoctoral Fellowship in Neuroscience, University of Florida, Gainesville, FL
2005 PhD in Neuroscience, Northwestern University Institute for Neuroscience, Evanston, IL
1995 BS in Biological Sciences, Michigan Technological University, Houghton, MI
Progression of histopathological and behavioral abnormalities following mild traumatic brain injury in the male ferret. Schwerin SC, Chatterjee M, Imam-Fulani AO, et al. J Neuro Res. 2018;96:556–572. https://doi.org/10.1002/jnr.24218
Establishing the ferret as a gyrencephalic animal model of traumatic brain injury: Optimization of controlled cortical impact procedures Schwerin, Susan C; Hutchinson, Elizabeth B; Radomski, Kryslaine L; Ngalula, Kapinga P; Pierpaoli, Carlo M; Juliano, Sharon L J Neurosci Methods. 2017 Jun 15;285:82-96. https://doi.org/10.1016/j.jneumeth.2017.05.010
Diffusion MRI and the detection of alterations following traumatic brain injury. Hutchinson EB, Schwerin SC, Avrarm AV, Juliano SL, Piepaoli C. J Neurosci Res. 2018 Apr;96(4):612-625. doi: 10.1002/jnr.24065. Epub 2017 Jun 13. Review. PMID: 28609579
Population based MRI and DTI templates of the adult ferret brain and tools for voxelwise analysis. Hutchinson EB, Schwerin SC, Radomski KL, Sadeghi N, Jenkins J, Komlosh ME, Irfanoglu MO, Juliano SL, Pierpaoli C. Neuroimage. 2017 May 15;152:575-589. doi: 10.1016/j.neuroimage.2017.03.009. Epub 2017 Mar 16. PMID: 28315740
Quantitative MRI and DTI Abnormalities During the Acute Period Following CCI in the Ferret. Hutchinson EB, Schwerin SC, Radomski KL, Irfanoglu MO, Juliano SL, Pierpaoli CM. Shock. 2016 Sep;46(3 Suppl 1):167-76. doi: 10.1097/SHK.0000000000000659. PMID: 27294688
Enhanced Motor Recovery After Stroke With Combined Cortical Stimulation and Rehabilitative Training Is Dependent on Infarct Location. Boychuk JA, Schwerin SC, Thomas N, Roger A, Silvera G, Liverpool M, Adkins DL, Kleim JA. Neurorehabil Neural Repair. 2016 Feb;30(2):173-81. doi: 10.1177/1545968315624979. Epub 2015 Dec 29. PMID: 26719353
Ipsilateral versus contralateral cortical motor projections to a shoulder adductor in chronic hemiparetic stroke: implications for the expression of arm synergies. Schwerin S, Dewald JP, Haztl M, Jovanovich S, Nickeas M, MacKinnon C. Exp Brain Res. 2008 Mar;185(3):509-19. Epub 2007 Nov 8. PMID: 17989973
Using paired pulse TMS to facilitate contralateral and ipsilateral MEPs in upper extremity muscles of chronic hemiparetic stroke patients. Schwerin SC, Yao J, Dewald JP. J Neurosci Methods. 2011 Feb 15;195(2):151-60. doi: 10.1016/j.jneumeth.2010.11.021. Epub 2010 Dec 4. PMID: 21134401
Motor map plasticity: A neural substrate for improving motor function after stroke Kleim JA, Schwerin S. Brain Repair After Stroke. 1-10. DOI: 10.1017/CBO9780511777547.002
B.S., Animal Sciences (1999), University of Massachusetts, Amherst
Ph.D., Molecular and Cellular Biology and Animal Sciences (2004), University of Massachusetts, Amherst
Post-doctoral Training, National Institute of Environmental Health Sciences, National Institutes of Health
The primary research goal of our lab is to understand how intracellular calcium signaling mechanisms regulate healthy cell and tissue physiology and disease pathogenesis. We address this using the fruit fly animal model, Drosophila melanogaster, which allows for a powerful combination of developmental genetics and in vivo analytical tools. Current projects in the lab include 1) regulation and functions of store-operated calcium entry in the heart; 2) roles of astrocyte calcium signaling in the response to nerve injury and development of neuropathic pain; 3) regulation of the morphology and dynamics of the endoplasmic reticulum, the primary calcium storage organelle in cells.
Petersen, C.E., Wolf, M.J., and Smyth, J.T. (2020) Suppression of store-operated calcium entry caused dilated cardiomyopathy of the Drosophila heart. Biology Open 9(3).
Karabasheva, D. and Smyth, J.T. (2019). A novel, dynein-independent mechanism focuses the endoplasmic reticulum around spindle poles in dividing Drosophila spermatocytes. Scientific Reports 9(1): 12456.
Karabasheva D and Smyth JT (2019). Preparation of Drosophila larval and pupal testes for analysis of cell division in live, intact tissue. Journal of Visualized Experiments, 159, e60961.
Smyth, J. T., T. A. Schoborg, Z. J. Bergman, B. Riggs and N. M. Rusan (2015). Proper symmetric and asymmetric endoplasmic reticulum partitioning requires astral microtubules. Open Biology 5(8).
Smyth, J. T., A. M. Beg, S. Wu, J. W. Putney, Jr. and N. M. Rusan (2012). Phosphoregulation of STIM1 leads to exclusion of the endoplasmic reticulum from the mitotic spindle. Current Biology 22(16): 1487-1493.
Smyth, J. T., J. G. Petranka, R. R. Boyles, W. I. DeHaven, M. Fukushima, K. L. Johnson, J. G. Williams and J. W. Putney, Jr. (2009). Phosphorylation of STIM1 underlies suppression of store-operated calcium entry during mitosis. Nature Cell Biology 11(12): 1465-1472.
INSTITUTION AND LOCATION DEGREE Completion Date FIELD OF STUDY
Madras University, India BS 6/1972 Chemistry
Madras University, India MS 6/1974 Biochemistry
Indian Institute of Technology, New Delhi, India Ph.D. 6/1980 Biochemistry
I received my Ph.D. degree from the highly respected Indian Institute of Technology in New Delhi, India, in Biochemistry. Following a post-doctoral year at Auburn University in Alabama with Dr. Peter Schoor studying benzo(a)pyrene metabolism, I went to the Biochemistry Department at Georgetown University to work as a Research Associate and later Research Instructor in the Department with Dr. Pat Fleming (now at Yale University School of Medicine). There I worked on the structure and function of cytochrome b561, a principal component of chromaffin granules and other types secretory vesicles in different mammalian tissues. Thereafter, I came to the Laboratory of Cell Biology and Genetics, NIDDK, NIH, to work with Dr. Harvey Pollard as a Senior Staff Fellow. In 1996, I was recruited by Dr. Pollard to join the Department of Anatomy and Cell Biology (now APG), as a Research Associate Professor.
My research has focused on the molecular basis of calcium signaling processes within cells. In early studies on chromaffin granules, which classically secrete catecholamines in response to a calcium pulse, attention was focused on the principal membrane protein cytochrome b561. This cytochrome is responsible for the unique process of vectorial electron transport across the membrane, and transfers electrons from ascorbic acid to dopamine beta hydroxylase (DBH) for the biosynthesis of norepinephrine from dopamine within the vesicle. I cloned the gene for this enzyme and interpreted the sequence in terms of a proposed transmembrane conformation. Later, when working in Dr. Pollard's lab looking for the human cytochrome b561 gene in a human library, I serendipitously isolated the long sought-for gene for human nucleolin. Aware of the critical importance of this gene for the maturation of ribosomes, I quickly moved to characterize and publish the description of this gene in the Journal of Biological Chemistry. This single author paper earned me an international reputation in a separate but related field of endeavor, in which I still contribute.
While at the NIH, I continued my interest in calcium signaling pathways by participating in the cloning the annexin 7 (ANX7) gene. Annexin 7 had been hypothesized to mediate calcium-activated membrane fusion occurring during exocytotic secretion. I determined that Anx7 was a single copy gene, characterized the exon-intron properties, and located the gene on chromosome 10q21(published in Biochemistry). I also extended this work to model organisms such as mouse and xenopus laevis, and discovered an ANX7 motif in HIV. The latter motif turned out to be of functional importance because deleting or replacing it resulted in loss of viability by the HIV virion (published in PNAS(USA)). Based on this and continuing work with site directed mutagenesis on human ANX7 by me, ANX7 is now known to be a Ca2+-activated GTPase with membrane fusion properties driven by not only calcium and GTP, but also PKC. In order to fully understand the function of the ANX7 gene in vivo, I also set about to prepare a knockout mouse for the Anx7 gene. As anticipated from the presumed importance of this gene, the Anx7(-/-) mouse had a lethal phenotype. However, the heterozygous Anx7(+/-) mouse was viable. However, the phenotype of this mutant mouse proved remarkable in terms of gender-specific growth characteristics: males grew to gigantic size. Specific organs in both males are females were very large. Islets of Langerhans were large enough to span the long axis of the pancreas. These islets of Langerhans were found to secrete insulin poorly, and to activate calcium signaling from intracellular pools quite inefficiently. In fact, the knockout mice had very low expression levels of the IP3Receptor located on the endoplasmic reticulum. (published in PNAS(USA)). Finally, when the Anx7(+/-) animals were approximately one year old they suddenly began to express tumors of various descriptions. On average, 30% of the mice developed these tumors, while none were noted in the normal littermate controls. I have conjectured that the deficiency in IP3R-dependent signaling might have consequences for defective apoptosis, since Ca2+ signaling through this channel is needed for the apoptotic process to occur in numerous biological examples.
I immediately turned to studies of human tumor cells and human tumors to see if the ANX7 gene were involved in neoplastic transformation or tumor biology. Initiating a collaboration with colleagues at NIH with tumor tissue microarrays, I discovered that ANX7 expression was vastly reduced prostate cancers characterized as hormone insensitive local recurrences or metastatic. Because of the large number of tumors access on the slides, approximately 1000 at a time, a P value for this conclusion was estimated to be P=.0001. I also found that about 30% of human prostate tumor cells had expressed either loss of heterozygosity (LOH, loss of one allele) or complete loss of both alleles for ANX7 (published in the PNAS(USA)). The method involved dissection of tumor cells from normal cells in samples of fresh-frozen prostate cancer, and analysis using the normal cells still in the sample of tumor tissue as controls. Thus, I was able to conclude that the mechanism of tumorigenesis might include mutational loss of at least one copy of the ANX7 gene. Interestingly, the locus of the ANX7 gene, 10q21, had been long hypothesized to contain an unknown tumor suppressor gene (TSG); I hypothesized that ANX7 might be this missing TSG. More recently, I have analyzed human breast cancers in the same way, and also found evidence of mutational loss of at least one of the two ANX7 alleles. Again, this occurred in about 30% of cases. In all cases, the loss of the ANX7 allele is accompanied by substantial reduction in expression by the remaining ANX7 gene.
In addition to this important work on the ANX7 gene, I have also being collaborating with Dr. Pollard and other colleagues in the Department on a study of cystic fibrosis. In particular, I developed genomic cDNA array technology for this and other Departmental use. The use of the arrays allowed me to conclude that the cause of massive lung damage in cystic fibrosis might be because of tonic upregulation of the TNFR/NFB pathway in affected lung epithelial cells (published in Molecular Medicine). The arrays developed by me have also been applied by me to studies on different tumor cell lines in which ANX7 gene expression is problematic, and collaboratively with other members of the Department and the University on important problems ranging from diabetes to brain injury.
Now, I am a skilled and experienced molecular biologist who has been at the cutting edge of research addressing the biology and biochemistry of the genes and proteins involved in kidney graft rejection, cancer, cystic fibrosis, inflammation, post-traumatic syndrome and major depressive disorder. I have extensive experience with cDNA microarrays, protein arrays, and antibody microarrays. Notably, I am the first author on the first paper to ever demonstrate the remarkable power of antibody microarrays for the identification of clinically relevant, low abundance serum biomarker proteins (Srivastava el al, 2006).
I have published my work in 90 peer reviewed articles. I am co-author of a patent on the ANX7 gene with Dr. Pollard and drug development for ERG fusion gene in Prostate cancer with Dr. Srivastava and Dr. Dalgard.
Srivastava, M., Duong Le T. and Fleming, P.J. (1984). Cytochrome b561 catalyzes transmembrane electron transfer. J. Biol. Chem.. 259: 8072-8075.
Srivastava, M., McBride, O.W., Fleming, P.J., Pollard, H.B. and Burns, A.L. (1990) Genomic organization and chromosoaml localization of the human nucleolin gene. J. Biol. Chem., 265:14922-14931.
Srivastava, M., Atwater, I., Glassman, M., Leighton, X., Goping, G., Miller, G., Mears, D., Rojas, E. and Pollard, H.B. (1999) Defects in IP3 Receptor Expression, Ca2+-Signaling and Insulin Secretion in the Anx7 (+/-) Knockout Mouse. Proc. Natl. Acad. Sci. 96,13783-13788
Srivastava, M., Bubendorf, L., L., Nolan, L., Glasman, M., Leighton, X., Koivisto, P., Willi, N., Gasser, T., Kononen, J., Sauter, G., Kallioniemi, O.P., Srivastava, S. and Pollard, H.B. (2001) ANX7, a candidate tumor-suppressor gene for prostate cancer. Proc. Natl. Acad. Sci. 98, 4575-4580.
Srivastava, M., Glasman, M., Leighton, X, Miller, G., Montagna, C., Reid, T., and Pollard, H.B. Genomic instability and gene expression profile in cancer prone Anx7(+/-) knockout mouse and cell line models. Proc Natl Acad Sci U S A. 2003; 100, 14287-14292.
Srivastava, M., Bubendorf , L., Raffeld, M., Bucher, C., Torhorst, J., Sauter, G., Olsen, C., Kallioniemi, O.P., Eidelman, E. and Pollard, H.B. Prognostic impact of ANX7-GTPase in metastatic and HER2 negative breast cancer patients. 2004 Clin. Can. Res 10:2344-50.
Srivastava, M., Eidelman, E Zhang, J Paweletz, C., Caohuy, H., Yang, O.F., Jacobson, K.A., Heldman, E, Huang, W., Jozwik, C., Pollard, B.S. and Pollard, H.B. Digitoxin mimics gene therapy with CFTR and suppresses hypersecretion of IL-8 from cystic fibrosis lung epithelial cells. Proc Natl Acad Sci U S A. 2004; 101, 7693-7698.
Torosyan Y, Dobi A, Naga S, Mezhevaya K, Glasman M, Norris C, Jiang G, Mueller G, Pollard H, Srivastava M. Distinct Effects of Annexin A7 and p53 on Arachidonate Lipoxygenation in Prostate Cancer Cells Involve 5-Lipoxygenase Transcription. Cancer Res. 2006 Oct 1;66(19):9609-16.
Torosyan Y, Dobi A, Glasman M, Mezhevaya K, Naga S, Huang W, Paweletz C, Leighton X, Pollard HB, Srivastava M. Role of multi-hnRNP nuclear complex in regulation of tumor suppressor ANXA7 in prostate cancer cells. Oncogene. 2010. 29(17):2457-66
Leighton X, Eidelman O, Jozwik C, Pollard HB, Srivastava M. ANXA7-GTPase as Tumor Suppressor: Mechanisms and Therapeutic Opportunities. Methods Mol Biol. 2017;1513:23-35.
• M.D. Binzhou Medical School, Shandong, China
• Ph.D. Biochemistry, Hebrew University, Jerusalem, Israel
• Postdoctoral Fellow: Neurology, Children’s Hospital/Harvard Medical School
• Tanaka M, Sackett S and Zhang Y. Endocannabinoid Modulation of Microglial Phenotypes in Neuropathology. Front Neurol. 2020 Feb 14;11:87.
• Tanaka M, Yagyu K, Sackett S and Zhang Y. Anti-inflammatory effects by pharmacological inhibition of knockdown of fatty acid amide hydrolase in BV2 microglia cells. Cells 2019, 8(5), 491
• Selvaraj P, Wen J, Tanaka M and Zhang Y. Therapeutic effect of a novel fatty acid amide hydrolase inhibitor PF04457845 in the repetitive closed head injury mouse model. Journal of Neurotrauma 2019 May 15;36(10):1655-1669.
• Tanaka M, Li H, Zhang X, Singh J, Dalgard C, Wilkerson M, and Zhang Y. Region- and time-dependent gene regulation in a PTSD-like mouse model by RNA-seq analysis. Molecular Brain 2019 Mar 28;12(1):25.
• Jones M, Wen J, Selvaraj P, Tanaka M, Moran S and Zhang Y. Therapeutic effect of the substrate selective COX-2 inhibitor IMMA in the animal model of chronic constriction injury. Frontiers in Pharmacology 2018; 9:1481.
• Wen J, Jones M, Tanaka M, Selvaraj P, Symes AJ, Cox B, Zhang Y. WWL70 protects against chronic constriction injury-induced neuropathic pain in mice by cannabinoid receptor-independent mechanisms. J Neuroinflammation. 2018; 15(1):9.
• Tanaka M, Moran S, Wen J, Affram K, Chen T, Symes AJ, Zhang Y. WWL70 attenuates PGE2 production derived from 2-arachidonoylglycerol in microglia by ABHD6-independent mechanism. J Neuroinflammation. 2017; 14(1):7.
• Wen J, Ariyannur P.S., Ribeiro R, Tanaka M, Moffett J.R., Kirmani B.F., Namboodiri A.M.A. and Zhang Y. Comparative effects of melatonin and N-acetylserotonin in the EAE model of multiple sclerosis. J Neuroimmune Pharmacol. 2016; 11:763-773.
• Wen J, Ribeiro R, Tanaka M and Zhang Y. Activation of CB2 receptor is required for the therapeutic effect of ABHD6 inhibition in the experimental autoimmune encephalomyelitis. Neuropharmacology 2015; 99:196-209.
• Tchantchou F, Tucker LB, Fu AH, Bluett RJ, McCabe JT, Patel S and Zhang Y. The fatty acid amide hydrolase inhibitor PF-3845 promotes neuronal survival, attenuates inflammation and improves functional recovery in mice with traumatic brain injury. Neuropharmacology 2014; 85:427-439.