Current Faculty

• 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-Doctoral Fellow 1976 1980 NINCDS, NIH

Dr. Anders is recognized as an international expert in photobiomodulation and has been invited to speak and chair sessions at numerous international laser conferences. She serves on the Executive Councils and Scientific Advisory Boards of several laser societies. She is a fellow of the American Society of Lasers in Medicine and Surgery since 2006. 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 currently is President of the American Society of Lasers in Medicine and Surgery. She serves on the Editorial Boards of Photomedicine and Laser Surgery, Lasers in Surgery and Medicine, Lasers in Medical Science, Physiotherapy Practice and Research and has published over 60 peer reviewed articles.

For more information about Dr. Anders' work, visit the Anders Laboratory Web Page.

Selected Recent Publications (2004 - Present)

Anders, J.J., Geuna, S. and S. Rochkind (2004) Phototherapy promotes regeneration and functional recovery of injured peripheral nerve. Neurol. Res., 26: 234-240.

Byrnes, KR, L. Barna, V. M. Chenault, R. W. Waynant, I.K. Ilev, L. Longo, C. Miracco, B. Johnson, and J.J. Anders (2004) Photobiomodulation improves cutaneous wound healing in an animal model of type II diabetes. Photomed. Laser Surg., 22: 281-290.

Ilev, I.K., R.W. Waynant, K. Byrnes and J.J. Anders (2004) A fiber-optic approach for in vivo minimally-invasive study of tissue optical properties. Proceedings SPIE., 5317: 147-150.

Byrnes, KR, R.W. Waynant, I.K. Ilev, X. Wu L. Barna, K. Smith, R. Heckert, Heather Gerst and J.J Anders (2005) Light promotes regeneration and functional recovery and alters the immune response after spinal cord injury. Lasers in Surg. and Med., 36: 171-185.

Byrnes, KR, X. Wu, R.W. Waynant, I.K. Ilev, and J.J. Anders (2005) Low power laser irradiation alters gene expression of olfactory ensheathing cells in vitro. Lasers in Surg. and Med., 37:161-171.

Amat, A., J. Rigau, R.W. Waynant, I. Ilev, J. Tomas and J.J. Anders (2005) Modification of the intrinsic fluorescence and the biochemical behavior of ATP after irradiation with visible and near-infrared light. J. Photochem. and Photobiol. B: Biology, 81: 26-32

Amat, A., J. Rigau, R.W. Waynant, I. Ilev and J.J. Anders (2005) The electric field induced by light can explain cellular responses to electromagnetic energy: a hypothesis of mechanism. J. Photochem. and Photobiol. B: Biology, 82: 152-160.

Hamblin, M.R., R.W. Waynant and J.J. Anders. (Editors) (2006) Proceedings of SPIE: 6140 Mechanisms for Low-Light Therapy, 222 pages.

Gopalendu, P., A. Dutta , K. Mitra, M. S. Grace, A.Amat, T. B. Romanczyk, X. Wu, K. Chakrabarti, J. J. Anders, E.Gorman, R. W. Waynant, Darrell B.Tata (2007) Effect of low intensity laser interaction with human skin fibroblast cells using fiber-optic nano-probes. J. Photochem. and Photobiol. B: Biology, 86: 252-261.

Tata, D.B., M. Fahey, K. Mitra, J.J. Anders, R.W. Waynant (2007) Near-Infrared Induced Suppression of Metabolic Activity in Aggressive Cancers. Proceedings of SPIE Vol. 6428, 64280E-1.

Dutta, A., K. Mitra, M. S. Grace, R. W. Waynant, D. B.Tata, E.Gorman, J. J. Anders (2007) Analysis of Biomodulaive Effects of Low Intensity Laser on Human Skin Fibroblast cells Using Fiber-Optic Nano-Probes. Proceedings of SPIE Vol. 6428, 64280D-1.

Hamblin, M.R., R.W. Waynant and J.J. Anders. (Editors) (2007) Proceedings In Biomedical Optics and Imaging: Mechanisms for Low-Light Therapy II. SPIE Vol. 6428.

Othon,C., M., X. Wu, J.J. Anders, and B. R.Ringeisen (2008) Single cell printing to form three dimensional lines of olfactory ensheathing cells. Biomedical Materials Special Issue: Advanced methods and protocols for the biomedical sciences. 3(034101):1-6. Anders, J.J, T. B. Romanczyk, Ilko K.Ilev, H. Moges, L. Longo, X. Wu, and R. W. Waynant (2008) Light Supports Neurite Outgrowth of Human Neural Progenitor Cells In Vitro: The Role of P2Y Receptors. IEEE Journal of selected Topics in Quantum Electronics, 14(1): 118-125.

Hamblin, M.R., R.W. Waynant and J.J. Anders. (Editors) (2008) Proceedings In Biomedical Optics and Imaging: Mechanisms for Low-Light Therapy III. SPIE Vol. 6846.

Hamblin, M.R., R.W. Waynant and J.J. Anders. (Editors) (2009) Proceedings In Biomedical Optics and Imaging: Mechanisms for Low-Light Therapy IV. SPIE Vol. 7161.

Wu, X., A.E. Dmitriev, M.J. Cardoso, A.G. Viers-Costello, R.C. Borke, J. Streeter, and J.J. Anders (2009) 810nm Wavelength Light: An Effective Therapy for Transected or Contused Rat Spinal Cord. Lasers in Surg. and Med., 41:36-41.

Moges, H., O.M. Vasconcelos, W.W. Campbell, R.C. Borke, J.A. McCoy, L. Kaczmarczyk, J. Feng and J.J. Anders (2009) Light therapy and Supplementary Riboflavin in the SOD1 Transgenic Mouse Model of Familial Amyotrophic Lateral Sclerosis(FALS). Lasers in Surg. and Med., 41:52-59.

Anders, J.J., H. Moges, X. Wu, I. Ilev, R. Waynant, and L. Longo (2010) The Combination of Light and Stem Cell Therapies: A Novel Approach in Regenerative Medicine. American Institute of Physics Proceedings, 1 226: 3-11.

Hamblin, M.R., R.W. Waynant and J.J. Anders. (Editors) (2010) Proceedings In Biomedical Optics and Imaging: Mechanisms for Low-Light Therapy V. SPIE Vol. 7552.

Hamblin, M.R., R.W. Waynant and J.J. Anders. (Editors) (2011) Proceedings In Biomedical Optics and Imaging: Mechanisms for Low-Light Therapy V. SPIE Vol. 7887.

Anders, J.J., H. Moges, X. Wu, I. Ilev, R. Waynant, and L. Longo (2010) The Combination of Light and Stem Cell Therapies: A Novel Approach in Regenerative Medicine. American Institute of Physics Proceedings, 1 226: 3-10. Laser Florence 2009, Editor L. Longo, AIP Conference Proceedings, Melville, NY

Moges H., Wu X., McCoy J., Vasconcelos O.M., Bryant H., Grunberg N.E., and J.J. Anders (2011) Effect of 810?nm light on nerve regeneration after autograft repair of severely injured rat median nerve. Lasers Surg Med. 43(9): 901-6. doi: 10.1002/lsm.21117.

Wu X., Alberico S., Moges H., De Taboada L., Tedford C., and J.J. Anders. (2012) Pulsed Light Irradiation Improves Behavioral Outcome in a Rat Model of Chronic Mild Stress. Lasers Surg Med. Lasers Surg Med. 44:227-232.DOI 10.1002/lsm.22004

Wu X., Moges H., DeTaboada L., and J.J. Anders. (2012) Comparable effects of pulsed and continuous wave light on axonal regeneration in a rat model of spinal cord injury. Lasers in Medical Science, 27:525-528.

Hamblin, M.R., R.W. Waynant and J.J. Anders. (Editors) (2012) Proceedings In Biomedical Optics and Imaging: Mechanisms for Low-Light Therapy VII. SPIE Vol. 8211.

Alcântara C.C., Gigo-Benato D., Salvini T., Oliveira A., Anders J.J., and T.L. Russo (2013) Effect of low-level laser therapy (LLLT) on acute neural recovery and inflammation-related gene expression after crush injury in rat sciatic nerve. Lasers in Surg and Med. 45: 246-252.

von Leden R., Cooney S., Ferrara T., Zhao Y., Dalgard C., Anders J.J., and K.R. Byrnes (2013) 808nm wavelength light induces a dose-dependent alteration in microglial polarization and resultant microglial induced neurite growth. Lasers in Surg and Med. 45: 253-263.

Wu X., W. E. Bolger, and J. J. Anders (2013) Fibroblasts Isolated from Human Middle Turbinate Mucosa Cause Neural Progenitor Cells to Differentiate into Glial Lineage Cells. PLoS ONE 8(10): e76926. doi:10.1371/journal.pone.0076926

Anders J.J., H. Moges, X. Wu 1, 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 in Surg and Med. 46: 34 -45.

Cellular and Molecular Mechanisms of Glial Cell

Dr. Armstrong's current research activities focus on the cellular and molecular mechanisms of glial cell development and regeneration. During development, one glial cell type, the oligodendrocyte, forms myelin which ensheaths axons to enable efficient neurotransmission in the CNS. Dr. Armstrong has studied the growth factors regulating the proliferation and migration of oligodendrocytes prior to myelin formation. Current experiments examine the differentiation of precursors of oligodendrocytes into mature oligodendrocytes, which express myelin-specific genes. This work is identifying proteins which bind to DNA and control transcription of genes expressed only in myelin-forming cells.

The proliferation, migration, and differentiation of oligodendrocytes are also being studied in adult animals after experimental myelin damage, or demyelination. Demyelination causes neurological dysfunction in several human diseases, the most common being multiple sclerosis. In multiple sclerosis myelin repair, or remyelination, is insufficient and recovery of function is incomplete. In the experimental model studied, demyelinated areas, with oligodendrocyte and myelin loss, are efficiently remyelinated. Dr. Armstrong is attempting to identify factors from lesioned areas which can induce cells around a lesion to proliferate and/or migrate into the lesion, and express myelin-specific genes, as required for myelination. It will be interesting to determine whether factors which control these processes during development will have the same roles in adult tissue during remyelination, and whether factors which are active in rodent experimental models of demyelination can also promote remyelination in human diseased issues.

• Ph.D., George Washington University, 1979

Plastic Responses of Neurons During Development and Regeneration

The research program in this laboratory is focused on plastic responses of motoneurons during development and regeneration. The major interest is to gain an understanding of developmentally-regulated substances that are re-expressed after nerve injury to adult motoneurons. Studies center on two different types of substances: those that are produced at high levels during ontogeny and either progressively decline to low levels or are not detectable in intact adult motoneurons. Developmental plasticity studies involve 1) defining profiles of gene expression and 2) determining the types of signal transfer mechanisms that regulate changes in the levels of expression of these substances during ontogeny. Experiments involve surgical and chemical manipulation of central (local neuropil environment around the motoneuron) and peripheral (injured nerve and its innervation target) developmental events to examine whether the down-regulation in intact motoneurons is coincident with a defined phase of glial/Schwann cell development and if it is controlled by events at the growing tip of the axon, the postsynaptic neuromuscular junction or presynaptic input to the motoneuron. The other phase of research is to investigate the role of these substances to changes in and around axotomized adult motoneurons that are considered germane to regeneration: whether the up-regulation of these substances influences anterograde (growing axonal tip at the injury site and reinnervation of the target site) and retrograde (glial reaction and afferent synaptic displacement) regenerative processes. Techniques utilized in carrying out this research program include general and stereotaxic surgery, neurotrophic factor or implants, immunocytochemistry, image analysis, the polymerase chain reaction, as well as horseradish peroxidase labeling and nerve stimulation to assay anatomic and functional reinnervation.

Recent Publications

Walsh, D. W., Ho, V. B., Borke, R. C. And Rovira, M., Anomalous Course of the Common Carotid Arteries: CT and MR( A) Illustration, Angiology 49: 235-238, 1998.

Nash, H. H., Borke, R. C. and Anders, J. J. A New Method of Purification for Establishing Primary Cultures of Ensheathing Cells from the Adult Olfactory Bulb. Glia 34, 81-87, 2001.

Nash, H. H., Borke, R. C. and Anders, J. J. Ensheathing Cells and Methylprednisolone Promote Axonal Regeneration and Functional Recovery in the Lesioned Adult Rat Spinal Cord, In Press J. of Neuroscience, 2002.

Snyder, S.K., Byrnes, K.R., Borke, R.C., Sanchez, A. and Anders, J.J. Quantitation of Calcitonin Gene-Related Peptide mRNA and Neuronal Cell Death in Facial Motor Nuclei Following Axotomy and Low Power Laser Treatment, In Press, Lasers in Surgery and Medicine, 2002.

• Ph.D., University of Pennsylvania, BA., Goucher College

Molecular Mechanisms of Retinal Gene Regulation and Function

Genes that are expressed at higher relative levels in a given tissue, or tissue region, are likely to be critical to specialized tissue function. Changes that alter the expression of these genes or their subsequent gene products may underlie tissue-specific diseases. Dr. Borst studies genes that are highly expressed in the eye; her laboratory is currently focused on three projects. Control of Interphotoreceptor Retinoid-Binding Protein (IRBP) gene expression in the retina.

IRBP is synthesized in the retina solely by the photoreceptor cells and is critical for proper retinal function. Study of IRBP gene expression and its regulation is important for understanding normal and disease related function in the retina. The long-term goal of this project is to define the DNA elements required for the control of the spatial and temporal expression of the IRBP gene.

Functional genomics of fovin

The fovea is located in the macular region of the retina and is the highly specialized area of the retina responsible for high acuity vision. Fovin is a novel, previously unidentified gene that is highly expressed in the fovea. We have determined fovin's DNA sequence, its expression profile and chromosomal localization. Fovin is found on chromosome 17 and is highly expressed in the retina and brain. The long-term objective is to determine fovin's function in health and disease.

Clinical manifestations of Type II diabetes in the eye

The fat sand rat, Psammomys obesus, is an excellent animal model for the study of Type II diabetes. In collaboration with Dr. Michelle Chenault, we are characterizing the changes that occur to the lens crystallins during the formation of diabetic cataracts. We are also investigating the role that glucose transporters may play in the development of diabetic cataracts and are determining if fat sand rats develop diabetic retinopathy.

• University of Strathclyde, Scotland, 1993

Regulation of Neuronal Excitability in the Amygdala Relevance to Epilepsy and Affective Disorders

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.

• San Diego State College, 1963, 1965; University of Arizona, 1973

Regulation of Neuronal Excitability in the Amygdala Relevance to Epilepsy and Affective Disorders

Research in this laboratory is directed toward understanding the electrophysiology of the vascular smooth muscle membrane and its relation to the etiology of hypertension. In vivo and in vitro studies are carried out using animals with hypertension and their respective normotensive controls to better understand the role of smooth muscle electrophysiology in the development and maintenance of hypertension. In some experiments, animals are treated with antihypertensive agents to ameliorate the hypertension and the effects of these antihypertensive agents on the smooth muscle membrane are examined. Other areas of research include: 1) measurement of membrane potentials using a fiber optic system and voltage-sensitive dyes. 2) Measurement of electrophysiological and biophysical properties of cultured NG108 neuroblastoma cells. Several ionic currents in these cells are sensitive to the presence of chemical agents. We are currently characterizing these currents under various experimental conditions to determine if these electrophysiological changes may allow the cells to be used as biological sensors.

• Ph.D., University of Pennsylvania, 2005

Mechanisms underlying protein dynamics and turnover

Proteolysis via the ubiquitin proteasome system (UPS) is a tightly regulated, rapid and effective mechanism for degrading specific proteins. Protein substrates are targeted for degradation by the proteasome through addition of a chain of ubiquitins. Ubiquitin conjugation is accomplished in sequential reactions, catalyzed by a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3). Attachment of a chain of 4 or more ubiquitins targets a protein for degradation by the proteasome. A single E1 enzyme transfers ubiquitin to all the E2s in the cell, and a small repertoire of E2s directly transfers ubiquitin to either an E3 or to a lysine residue on the substrate. The E3s are primarily responsible for conferring substrate specificity.

Many neurodegenerative diseases result from insufficient levels of essential proteins or a buildup of toxic ones. These neurodegenerative diseases include disorders in which the pathological proteins may accumulate as is the case with polyglutamine expansion disease proteins, α-synuclein in Parkinson's disease, and tau and amyloid-β (Aβ) in Alzheimer's disease or diseases resulting from deficiency of essential proteins as in spinal muscular atrophy and muscular dystrophy. Understanding the molecular basis of protein degradation and developing strategies to manipulate these processes is thus important in developing treatments for a myriad of diseases.

A fundamental question with relevance to many neurodegenerative diseases is how disease proteins are targeted for degradation. Research in this area has been limited by the fact that (i) most of the current compounds target the catalytic sites of the proteasome and have significant associated toxicity whilst only a few target the enzymes that selectively tag a protein for degradation (ii) many compounds that target the UPS, when given systemically, do not enter the central nervous system (CNS) in appreciable levels, and (iii) the role of the UPS in the development and maintenance of neurons is not very well understood.

Our goal is to begin answering some of these outstanding questions using genetic and biochemical techniques.

• Ph.D., Uniformed Services University of the Health Sciences, 2003

Traumatic Brain and Spinal Cord Injury: Post-Injury Inflammation and Metabolic Changes

The research in Dr. Byrnes' laboratory focuses on the mechanisms of inflammation following traumatic brain and spinal cord injury using animal modeling, non-invasive imaging, behavioral assessments and a variety of therapeutic approaches.  There are two major lines of investigation currently ongoing in the lab:

1.      The role of NADPH oxidase in recovery after spinal cord injury.  Spinal cord injury (SCI) results in both acute and chronic inflammation.  This inflammation includes activation of microglia, invasion of macrophages and activation of the NADPH oxidase (NOX) enzyme.  We have previously shown that NOX, particularly the NOX2 and 4 isoforms, are up-regulated after central nervous system (CNS) injury in a number of cells, including microglia and macrophages.  This enzyme is responsible for producing reactive oxygen species, and contributes to oxidative stress that can lead to further inflammation, neuronal damage and impairment of recovery.  The lab is now investigating the mechanism behind NOX activation, the effects of inhibition of the NOX enzyme, and the role of NOX in aging with SCI, using both animal and cell culture models, as well as behavioral, histological, magnetic resonance imaging, and biochemical outcomes. 

2.      The role of glucose uptake in outcome after brain and spinal cord injury.  Previously, we have shown that a single mild traumatic brain injury (mTBI) results in a transient reduction in brain glucose uptake as measured by [¹⁸F]fluorodeoxyglucose (FDG) with positron emission tomography (PET).  This transient reduction in uptake is maximally depressed at 24 hours post-injury with a return to baseline level by 16 days.  Glucose uptake impairments have been correlated with impairments in motor function, cognitive function and glial activation.  The lab is now investigating the correlation of glucose uptake alterations with outcome after a repeated mTBI model and after spinal cord injury.  In addition, the lab is investigating novel therapeutic approaches to improve glucose uptake and alter recovery after injury.

Pubmed Link (http://www.ncbi.nlm.nih.gov/pubmed?term=Byrnes%20KR[Author])

Profile

Kwang Choi, Ph.D., is an Assistant Professor of Psychiatry at the Uniformed Services University of the Health Sciences in Bethesda, Maryland. Dr. Choi received B.S. and M.A. in Biology from the Dongguk University in South Korea and Ph.D. in Neuroscience and Psychiatry from the University of Alberta in Edmonton, Canada. He completed a postdoctoral work at the Dept of Psychiatry of the University of Texas Southwestern Medical Center at Dallas, TX, and worked as a Scientist in the Stanley Laboratory of Brain Research, Rockville, MD.

The long-term goal of Dr. Choi's research is to better understand the biological mechanisms of stress, anxiety and substance abuse. He is conducting a translational research using clinically relevant animal models of stress and drug abuse as well as postmortem brain tissue of psychiatric patients including mood and anxiety disorders. He is currently using various animals models such as intravenous drug self-administration and fear/anxiety behavior as well as non-invasive brain imaging technology (FDG-PET and MRI) to study molecular mechanisms of comorbid anxiety disorders and substance abuse. These approaches complement each other by elucidating the neurobiological mechanisms mediated by biological and environmental factors contributing to vulnerability or resilience to fear/anxiety and substance abuse. By identifying the mechanisms in which drugs and environment interact, and change the brain to lead to psychiatric symptoms, we can develop improved treatments of a comorbid substance abuse and anxiety disorders.

Selected Publications

Choi KH, Clements RLH, Greenshaw AJ (2005) Simultaneous AMPA/kainite receptor blockade and dopamine D2/3 receptor stimulation in the nucleus accumbens decreases brain stimulation reward in rats. Behav. Brain Res. 158:79-88

Choi KH, Elashoff M, Higgs BW, Song J, Kim S, Sabunciyan S, Diglisic S, Yolken RH, Knable M, Torrey EF and Webster MJ (2008) Putative psychosis genes in the prefrontal cortex: combined analysis of gene expression microarrays. BMC Psychiatry 8:87

Choi KH, Zepp ME, Higgs, BW, Weickert CS, Webster MJ (2009) Expression profiles of schizophrenia susceptibility genes during human prefrontal cortex development. J. Psychiatry and Neuroscience 34:450

Choi KH, Higgs BW, Wendland JR, Song J, McMahon FJ, Webster MJ (2011) Gene expression and genetic variation data implicate PCLO in bipolar disorder. Biological Psychiatry 69:353-9

Choi KH, Edwards, S, Graham, DL, Han, MH, Larson, EB, Whisler, KN, Simmons, D, Rahman, Z, Monteggia, LM, Eisch, AJ, Neve, RL, Nestler, EJ, Self, DW (2011) Reinforcement-Related Regulation of AMPA Glutamate Receptor Subunits in the Ventral Tegmental Area Enhances Cocaine Reinforcement. Journal of Neuroscience, 31:7927–7937

Choi KH, Le T, McGuire J, Xing G, Zhang L, Li H, Parker CC, Johnson LR and Ursano RJ (2012) Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear. J Psychiatric Research, 46:882-889

Profile

Our laboratory studies the biochemical events that occur following the activation of the mu opioid receptor. It is known that morphine relieves severe pain by activating mu opioid receptors throughout the nervous system. It is also known that repeated exposure of mu opioid receptors to morphine results in an attenuation in the ability of morphine to relieve pain. Our laboratory is also interested in studying the biochemical events that result in the 'desensitization' of the mu receptor signalling system.

When the mu opioid receptor binds an opiate (such as morphine), a series of other proteins associated with the mu receptor signalling pathway become activated. The first protein activated by the morphine-bound mu receptor is a GTP-binding protein (G protein). The G protein requires guanosine triphosphate (GTP) to be active. When the GTP is hydrolyzed to guanosine diphosphate (GDP), the protein becomes inactive. There are a number of different types of G proteins in neurons, and the specific types of G proteins that associate with the mu opioid receptor have recently been identified by our laboratory. We are also investigating how chronic exposure of the mu receptor to morphine results in a diminished responsiveness of neurons to opiates (tolerance). Recently, a new group of proteins has been discovered in the nervous system. These proteins are capable of increasing the rate of hydrolysis of GTP that is bound to G proteins. When GTP is rapidly hydrolyzed, the signalling pathway shuts down. These new proteins that increase the hydrolysis of GTP are called RGS proteins (for Regulators of G protein Signalling). We are interested in determining if chronic morphine administration can increase the synthesis of these RGS proteins and/or cause these RGS proteins to become associated with the G proteins that mediate the effects of the mu receptor.

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Chronic exposure of the mu opioid receptor to morphine results in the interaction of RGS proteins with the G proteins that normally mediate the effects of the mu opioid receptor. The RGS protein inhibits the activity of the G protein by stimulating the hydrolysis of GTP to GDP.

Our laboratory has recently developed antibodies that can selectively immunoprecipitate the mu opioid receptor in an active state in order to co-purify proteins that associate with the mu receptor. These antibodies were raised against fusion proteins that contained 50 to 61 amino acid regions that occur in the mu opioid receptor. These antibodies are currently being used to purify soluble, active mu opioid receptors in association with their interactive G proteins. During this past year, we have identified Gao and Gai1 as the most prominent G proteins that co-precipitate with the rat brain mu opioid receptor. We are also interested in determining if chronic morphine treatment can cause RGS proteins to become associated with the mu receptor/G protein complex. To accomplish this goal, we are also developing antibodies against the newly discovered RGS proteins. Finally, during the coming year, we will be transfecting cells that express the mu opioid receptor with selected RGS proteins to determine if expression of these proteins can diminish mu opioid receptor signalling.

Selected Publications:

Weems, H.B., Chalecka-Franaszek, E., and Cote, T.E. (1996) Solubilization and pharmacological characterization of high affinity, guanine nucleotide sensitive mu-opioid receptors from rat brain. J. Neurochem. 66, 1042-1050.

Chalecka-Franaszek, E., Weems, H.B., Crowder, A.T., Cox, B.M., and Cote, T.E. (2000) Immunoprecipitation of high-affinity, guanine nucleotide-sensitive, solubilized mu opioid receptors from rat brain: co-immunoprecipitation of the G proteins Gao, Gai1 and Gai3. J. Neurochem. 74:1068-78.

Profile

Opiate drugs are indispensable therapeutic agents in the treatment of severe and chronic pain. They act at receptors normally utilized by members of a family of naturally occurring peptides, the endogenous opioid peptides. Several peptides fall into this group, including the enkephalins, ?-endorphin, and dynorphin. A structurally related peptide, nociceptin (also called orphanin FQ; abbreviated N/OFQ) was identified in 1995. Endogenous opioids and N/OFQ act through a set of specific receptors as neural regulators in many parts of the central and peripheral nervous systems. The regulatory role of opioid receptors in pain pathways accounts for the potent analgesic actions of opiate drugs such as morphine. These peptides and their receptors are also important regulators of the central pathways mediating behavioral reinforcement, and thus play a role in the reward mechanisms associated with satisfaction of our needs for fluid replacement, maintained nutrition and reproduction of the species. This makes opioid receptors participants in drug addictions not only for opiate drugs such as heroin but also in the reinforcing actions of other drugs of abuse such as ethanol, amphetamines, cocaine and marijuana. Opioid-regulated neurons show very marked adaptations to chronic opiate drug exposure, resulting in the development of tolerance, physical dependence, and addiction.

Click to view larger image

In recent studies, we have found that the expression of enkephalins, N/OFQ, their precursor peptides and their mRNAs are significantly increased in neurons and/or glial cells following neuronal activation or exposure to cytokines, to oxidative stress, or ischemia and re-perfusion. In neurons, expression of these peptides is increased by neuronal depolarization or elevation of intracellular calcium. It is not surprising, therefore, that N/OFQ levels are increased in brain by mechanical injury, seizures or neurotoxic agents including those inducing symptoms closely reminiscent in Parkinson's Disease. We are now studying the expression and functions of N/OFQ and other opioids in regulating central dopamine neurons in experimental models of Parkinson's Disease, or after seizure generation.

• Molecular and Cell Biology Program
• Neuroscience Program
• Course Director, Techniques in Neuroscience
• Course Director, Advanced Topics in Genomics and Proteomics
• Education: B.A. (1997) in Molecular and Cell Biology, University of California
• at Berkeley; Ph.D. (2005) in Neuroscience, Uniformed Services University,
• Postdoctoral Fellowship, University of California at San Francisco

Memory Adaptive Immunity in Mild Traumatic Brain Injury

Despite the appearance of health, individuals that have recovered from mTBI may be susceptible to worse outcome after a subsequent second injury and may even result in sudden coma or death. Recently, it has been determined that the adaptive immune system can respond and develop memory to CNS injury and activate production of autoantibodies with pathogenic potential. However, the precise response and contribution of memory immune responses in pathogenesis after repeated mTBI events has not been investigated. Our laboratory focuses on the role of memory components of the adaptive immune system in mTBI. We are currently defining a role of memory lymphocyte generation on neuroinflammation and injury outcome in a model of repeated mTBI. Systems biology level evaluation of brain, spleen, lymph node, and peripheral blood lymphocyte populations are accomplished using multi-dimensional flow cytometry, complete transcriptome analysis by RNA-seq, and multiplex ELISA analysis of in vitro lymphocyte restimulation assays. In vitro lymphocyte cultures from experimental subjects are being utilized for identification of brain-associated immunogenic antigens in repeated mTBI. Since T and B lymphocytes have both potential neuroprotective and neuropathogenic roles, elucidating the response of the adaptive immune system to mTBI is of importance to develop preclinical strategies to improve neurological recovery after repeated injury.

Patricia Deuster, PhD, MPH, CNS, is a Professor and Director for the Consortium for Health and Military Performance (CHAMP) in the Department of Military and Emergency Medicine, and for the Human Performance Resource Center (HPRC), at the Uniformed Services University of the Health Sciences, Bethesda, MD. She was the author of the first U.S. Navy SEAL Nutrition Guide sponsored by U.S. Special Operations Command and, because of its success, was commissioned to update the nutrition guide for the United States Special Operations Commands (USSOCOM).

Dr. Deuster, a Certified Nutrition Specialist, has conducted research in the area of sports and warrior nutrition for over 25 years and has published well over 100 peer-reviewed papers relating to stress, nutrition, and physical performance in the military. She has been a tennis professional, nationally ranked marathoner, qualifier for the First Women's Olympic Marathon Trials, triathlete, skydiver with over 100 jumps, and world-wide scuba diver. In addition, she is an invited speaker throughout the country on sports nutrition and performance.

Neurogenesis is the process by which neurons are generated from neural stem cells. The vast majority of mammalian neurogenesis occurs during embryonic and early postnatal development but new neurons are continually generated in two discrete brain regions in adults.

We are interested in understanding the processes that regulate neurogenesis in the developing and adult brain and how neurogenesis can be used in therapeutic interventions to promote brain repair.

Current research projects in the lab focus on three topic areas: 1) transcription factor programs regulating neurogenesis, circuitry organization and function in the developing mouse cerebellum; 2) epigenetic mechanisms regulating neurogenesis in the brains of adult mice; 3) human neural stem cell-based approaches to treat traumatic brain injury.

Our goal is to contribute knowledge to the development of new therapies to promote brain repair. To achieve this goal our research uses a combination of genetic, epigenetic, biochemical, histological, electrophysiological and behavioral techniques.

Dr. Galdzicki uses a molecular and electrophysiological approach to understanding mental retardation in trisomy 21 or Down syndrome.

Down syndrome (DS) is the most common viable human autosomal chromosomal abnormality. It is the result of a third chromosome 21, instead of the usual pair. This disorder leads to a specific physical appearance, mild to moderate mental retardation and sensory function deficits.

Using mouse models, his lab studies signal transduction pathways, synaptic plasticity, electrophysiological, and optical and molecular techniques in order to understand the causes of impaired hippocampal function. To the extent that abnormalities in the trisomic mouse model of DS represent changes in the human DS brain, Dr. Galdzicki's research can provide new clues on the causes of mental retardation in DS and helps to further understand the plasticity of neuronal networks in general and inhibitory networks, in particular. Furthermore, because people with Down syndrome have less frequent occurrences of many types of cancer, the Galdzicki team and his collaborators are also looking for cues that may lead to better strategies for treating cancer in the general population.

Post-Traumatic Stress Disorder

At present, there is no definitive treatment and there is no cure for Post Traumatic Stress Disorder because the molecular targets of PTSD remain undetermined.

Dr. Galdzicki's research activities focus on developing therapeutic applications of microRNAs to reverse an abnormal synaptic plasticity profile caused by stress and to alleviate anxiety episodes in military and/or civilian individuals suffering with post-traumatic stress disorder.

The neurological functions of PTSD victims are strongly impacted, especially with changes reported in the limbic system. Dr. Galdzicki and his team of researchers together with collaborators seek to address the important challenges facing clinical research in its quest to help those suffering with PTSD. By studying the microRNA profiles of animal models, Dr. Galdzicki aims to broaden PTSD knowledge and to find ways to effectively treat this mental health disorder or to reduce its consequences.

Epigenetic mechanisms of exposure to heavy metals and traumatic brain injury

Although the biological effects of the heavy metal, tungsten, are not well known, reports indicate that exposure may affect memory, evokes the occurrence of seizures, and change the expression of genes implicated in neuronal signaling and apoptotic pathways. Traumatic brain injury may affect similar targets.

The Dr. Galdzicki's team hypothesizes that exposure to tungsten alloys and mild TBI causes a specific set of epigenetic modifications which lead to impairments in physiological properties, synaptic plasticity and memory mechanisms.

To this end, Dr. Galdzicki and a team of researchers are conducting experiments designed to identify the mechanisms underlying tungsten alloy's biological activity in the central nervous system. These efforts may help to prevent potential neurotoxicity, assess impact on synaptic plasticity and neuronal network activity, understand potential contributions to neurological symptoms afflicting US veterans, and identify effective therapies to reverse the consequences of exposure to tungsten alloy and potential long-term synergism with TBI in military personnel and civilians.

Profile

Neil E. Grunberg, Ph.D., is Professor of Military & Emergency Medicine (MEM), Medical & Clinical Psychology (MPS), and Neuroscience (NES) in the Uniformed Services University (USU) School of Medicine (SOM); Professor in the Graduate School of Nursing (GSN); Director of Research and Development in the USU Leadership Education and Development (LEAD) program; and Director of Faculty Development for MEM. He is a medical and social psychologist who has been on faculty at USU since 1979.  His role in LEAD is to ensure that the LEAD program and sessions are based upon sound evidence and scholarship and to oversee original research relevant to leadership education and training.

Dr. Grunberg earned baccalaureate degrees in Medical Microbiology and Psychology from Stanford University (1975); earned M.A. (1977), M.Phil. (1979), and Ph.D. (1980) degrees in Physiological and Social Psychology from Columbia University; and received doctoral training in Pharmacology at Columbia University’s College of Physicians & Surgeons under a National Research Service Award (NRSA, 1976-79). Dr. Grunberg helps train physicians, psychologists, and nurses to serve in the Armed Forces or Public Health Service, and scientists for research positions. He has published >180 papers addressing behavioral medicine, stress, and leadership. Dr. Grunberg has received awards from the U.S. Surgeon General, CDC, FDA, American Psychological Association, NIH, Society of Behavioral Medicine, and USU. He has served as President of the USU Faculty Senate and has chaired USU committees including: Strategic Planning; Manpower; Health, Safety, and Wellness; Appointment, Promotions, and Tenure. Outside USU, he has chaired Working Groups for the MacArthur Foundation and Robert Wood Johnson Foundation. In 2015, Dr. Grunberg was selected as a Presidential Leadership Scholar (PLS).

Research and Teaching

Dr. Grunberg and his research group study leadership, stress (psychological and physical, including mTBI and PTSD), and appetitive behaviors (including nicotine, alcohol, caffeine, and food consumption).

SOM Education and Training: Introduction to leadership; Effective communication; Communicating difficult information; Team building; Stress, performance, and leadership; Leadership in medical field practicum; Sports psychology.

Graduate Student Teaching:  Appetitive & Addictive Behaviors, Advanced Topics and Techniques in Neuroscience, Behavioral Neuroscience, Advanced topics in Social Psychology; Interprofessional research.

Mentoring: Dr. Grunberg has supervised 33 doctoral dissertations in Medical Psychology, Clinical Psychology, and Neuroscience, and has served on many master and doctoral degree committees. He currently is training three Clinical Psychology Ph.D. students and two GSN Ph.D. students. In addition, he mentors faculty members in MEM in his role as MEM Director of Faculty Development.

Selected Recent Publications

Yarnell, A.M, Shaughness, M.C., Barry, E.S., Ahlers, S.T., McCarron, R.M., Grunberg, N.E. (2013). Blast traumatic brain injury in the rat using a blast overpressure model. Current Protocols in Neuroscience. Chapter 9, Unit 9.41.

Deuster, P.A., Grunberg, N.E., & O'Connor, F.G. (2014). Human performance optimization: An integrated approach for Special Operations. Journal of Special Operations Medicine, 14, Edition 2, 2-7.

Hamilton, K.R., Elliott, B.M., Berger, S.S., & Grunberg, N.E. (2014). Environmental enrichment attenuates nicotine behavioral sensitization in male and female rats. Experimental and clinical psychopharmacology, 22(4), 356.

Sharma, A., Chandran, R., Barry, E.S., Bhomia, M., Hutchison, M.A., Balakathiresan, N.S., Grunberg, N.E., & Maheshwari, R.K. (2014). Identification of serum microRNA signatures for diagnosis of mild traumatic brain injury in a closed head injury model. PLoS One. 9(11): e112019.

O'Connor, F.G., Grunberg, N.E., Kellermann, A.L., & Schoomaker, E. (2015). Leadership education and development at the Uniformed Services University. Military Medicine, 180(4S), 147-152.

Turtzo, L.C., Budde, M.D., Dean, D.D., Gold, E.M., Lewis, B.K., Janes, L., Lescher, J., Coppola, T., Yarnell, A., Grunberg, N.E., & Frank, J.A. (2015). Failure of intravenous or intracardiac delivery of mesenchymal stromal cells to improve outcomes after focal traumatic brain injury in the female rat. PLoS One. 10(5): e0126551.

Nindl, B.C., Jaffin, D.P., Dretsch, M.N., Cheuvront, S.N., Wesensten, N.J., Kent, M.L., Grunberg, N.E., Pierce, J.R., Barry, E.S., Scott, J.M., & Young, A.J. (2015). Human performance optimization metrics: Consensus findings, gaps, and recommendations for future research. The Journal of Strength & Conditioning Research, 29, S221-S245.

Yarnell, A.M., Barry, E.S., Mountney, A., Shear, D., Tortella, F., & Grunberg, N.E. (2016). The revised neurobehavioral severity scale (NSS-R) for rodents. Current Protocols in Neuroscience.

Callahan, C., & Grunberg, N.E. (in press). “Military medical leadership,” in E.B. Schoomaker and D.C. Smith (Eds.), Fundamentals of Military Medical Practice. Washington, DC: Borden Institute. 

Yarnell, A.M., Dullea, C., & Grunberg, N.E. (in press). “Military communication,” in E.B. Schoomaker and D.C. Smith (Eds.), Fundamentals of Military Medical Practice. Washington, DC: Borden Institute. 

Yarnell, A.M., Barry, E.S., & Grunberg, N.E. (in press). “Psychological well-being,” in E.B. Schoomaker and D.C. Smith (Eds.), Fundamentals of Military Medical Practice. Washington, DC: Borden Institute.

Yarnell, A.M., & Grunberg, N.E. (in press). “Developing ‘Allostatic leaders’: A Psychobiosocial Perspective,” in M. Clark & C.W. Gruber (Eds.), Leader Development Deconstructed, Cham, Switzerland: Springer International Publishing.

Grunberg, N.E., Barry, E.S., Kleber, H., McManigle, J.E., Schoomaker, E.B., (in press). “Seven steps to establish a leader and leadership education and development (LEAD) program,” in M. Clark & C.W. Gruber (Eds.), Leader Development Deconstructed, Cham, Switzerland: Springer International Publishing.

Professional Activities

Selected Professional Activities: Dr. Grunberg is a fellow of the American Psychological Association, Academy of Behavioral Medicine Research, and Society for Behavioral Medicine. He is a founding member of the Society for Research on Nicotine and Tobacco, and a member of the Association for Psychological Science, the Society for Neuroscience, Sigma Xi, and the Academy of Medicine of Washington, D.C. He has been an editor for Addiction, Annals of Behavioral Medicine, Nicotine and Tobacco Research, and US Surgeon Generals' Reports. He serves as a scientific consultant to the Maryland Tobacco Prevention and Cessation Resource Center, the Maryland Smoking Cessation Quitline (MD Quit), and the Maryland State Mental Health and Substance Abuse treatment programs. He is a member of the Society of Behavioral Medicine's Wisdom Council, the editorial board of Pharmacology Biochemistry and Behavior, and a contributing reviewer to F1000 (an electronic biomedical research journal source).

Selected Awards

American Psychological Association's Outstanding Contributions to Health Psychology (1989)

Centers for Disease Control Awards (1988, 1990), US Surgeon General's Medallion (1990)

USU Outstanding Biomedical Graduate Educator Award (1999, 2008)

US FDA Research Award (2005), Society of Behavioral Medicine Distinguished Scientist Award (2006)

USU Center for Health Disparities Building Partnerships for Better Health Award (2006)

USU Carol J. Johns Award to enhance USU programs, faculty, and reputation (2007)

USU Cinda Helke Award for Graduate Student Advocacy (2008)

United States Presidential Leadership Scholar (2015)

USU awards for Medical Student Teaching, Research Mentoring, Distinguished Service, and Outstanding Performance. 

Profile

The Johnson Lab in the department of Psychiatry and interdepartmental Neuroscience program seeks to address fundamental questions in the neurobiology of fear memory with the aim of providing vital basic knowledge into the way the brain encodes normal and pathological fear memories.

Normal fear memory and fear responses are an essential part of any persons or animals survival mechanism. Using fear memory an organism can learn to associate and remember new threats with physical danger. Fear pathology includes the anxiety disorders and post traumatic stress disorder (PTSD). Anxiety and PTSD can be characterized by pathology in fear memory where responses are amplified and become debilitating. These disorders can thus be thought of as either pathology of the acquisition of fear memory or as pathology in the expression of an otherwise normal fear memory.

Knowledge of where and how the brain processes fear and fear learning has greatly increased in the last few decades driven by the work of LeDoux, Davis, Pare, Fanslow, Phelps, Maren and many others. This research has identified neural circuits that mediate synaptic plasticity at input synapses to the lateral amygdala (LA). However, knowledge of the cellular encoding of fear memory within the LA network is crucially lacking. The Johnson Lab seeks to quantify the neural circuits of the LA and also the organization of fear memories encoded by groups of LA neurons. The lab has coined this approach the study of the Micro Anatomy of Fear.

In addition the Johnson Lab also seeks to directly understand the microanatomy of how stress interacts with the fear system. One of the key mechanisms of the stress response is regulation of the HPA axis including modulation of adrenal steroids. The Johnson lab also investigates the microanatomy of glucorticoid receptors and their regulation of LA network behavior.

The Johnson lab studies the microanatomy of fear using Pavlovian Fear Conditioning as a principal behavioral model. Brains subject to Pavlovian conditioning are studied using 3-dimensional reconstruction of LA neural networks. 3D mapping is performed using computerized mapping with Neurolucida (Microbrightfield, VT). Anatomical and electrophysiological data is obtained from neurons and networks using immunocytochemistry and whole cell patch clamp and extra cellular field recordings. Structural data is obtained using transmitted light, fluorescent and electron microscopy.

• University of Pennsylvania, 1982

Neural Plasticity in Developing and Adult Cerebral Cortex

The interests of Dr. Juliano's laboratory center on factors mediating adult and developmental plasticity of the neocortex. Two streams of research occur simultaneously in the lab. The first studies development of the cerebral cortex and focuses on factors important in migration and differentiation of cells in the cortical layers. The lab is particularly interested in the role of radial glia that guide neurons into the cerebral cortex and in Cajal Retzius cells that signal positional information to migrating neurons. Current studies include organotypic culture preparations from animal models with disrupted layer formation to study: i) factors that maintain radial glial fibers, ii) factors involved in growth of thalamic fibers into normal and disrupted cortex, and iii) the possibility of cortical repair by repopulation with appropriately timed progenitor cells. The second stream of research evaluates conditions that mediate plasticity in adult cerebral cortex. The lab is interested in the interaction between acetylcholine and neurotrophic factors that allow the cerebral cortex to improve functional responses after lesions/disease that normally result in reduced cortical capacity. They are using genetically engineered cell lines or other vectors to deliver neurotrophins into the cerebral cortex.

Profile

Associate Professor, Dept. of Psychiatry and Neuroscience Program

The ultimate goal of my research is to acquire and provide the knowledge that is necessary for the development of novel and effective molecular and pharmacological means that will prevent or treat stress-related affective disorders, such as post-traumatic stress disorder (PTSD). Many lines of evidence have suggested a central role of the amygdala in stress-related emotional illnesses and PTSD. In fear conditioning (an experimental paradigm that is similar to PTSD and other anxiety disorders), the amygdala appears to be the site of emotional memory storage. The amygdala also plays a
very important role in modulating the consolidation on emotional memory. In PTSD patients, the amygdala displays hypertrophy and hyperexcitability. For these reasons, my research program has been centered in the amygdala cellular neurobiology. My objectives are as follows:

• To understand the neuronal physiology and mechanisms of synaptic plasticity in the amygdala.  Included in this objective is the identification of the role of neuromodulators that are known to affect emotional behavior and affective disorders.
• To determine how amygdala physiology and plasticity are altered following exposure to a stressor that mimics traumatic stressors that result in PTSD.  The accomplishment of this objective requires the use of an appropriate animal model. The inescapable tail-shock paradigm in rats that I have developed in my laboratory has been shown to induce elevated basal corticosterone levels, weight loss, deficits in escape/avoidance learning and an exaggerated startle response, all of which have been observed in PTSD patients.
• To develop pharmacological interventions that will prevent or treat stress-induced pathophysiological alterations of the amygdala.  To date, my research group has made significant strides in the accomplishment of these objectives. There is significant potential
  for the development of improved strategies for the prevention and/or treatment of PTSD based on the research carried out in my laboratory.

Recent Publications

1. Post, R.M., Weiss, S.R., Smith, M., Li, H. & McCann, U.: Kindling versus quenching: Implications for the evolution and treatment of posttraumatic stress disorder. Ann. N.Y. Acad. Sci. 821:285-295, 1997.

2.     Post, R.M., Weiss, S.R.B., Li, H., Smith, M.A., Zhang, L.X., Xing, G., Osuch, E.A. & McCann, U.D.: Neural plasticity and emotional memory. Development and Psychopathology, 10: 829-855, 1998.

3.     Li, H. & Henry, J.L.: Adenosine A2 receptor mediation of pre- and postsynaptic excitatory effects of adenosine in hippocampus in vitro. European Journal of Pharmacology, 347(2-3): 173-182, 1998.

4.    Li, H. & Rogawski, M.A.: GluR5 mediated synaptic transmission in basolateral amygdala in vitro. Neuropharmacology, 37: 1279-1286, 1998.

5.    Li, H., Weiss, S.R.B., Chuang, D-M., Post, R.M. & Rogawski, M.A.: Bidirectional synaptic plasticity in the rat basolateral amygdala: characterization of an activity-dependent switch sensitive to the presynaptic metabotropic glutamate receptor antagonist 2S-α-Ethylglutamic acid. The Journal of Neuroscience, 18(5): 1662-1670, 1998.

6.        Post, R.M., Weiss, S.R.B., Li, H., Leverich, G.S. and Pert, A.: Sensitization components of post-traumatic stress disorder: implications for therapeutics. Seminars in clinical neuropsychiatry, 1999 Oct;4(4):282-94. Review.

7.        Post, R.M., Speer, A., Weiss, S. and Li, H.:  Seizure Models: Anticonvulsant effects of ECT and rTMS.   Progress in Neuropsychopharmacology and Biological Psychiatry, 2000 Nov;24(8):1251-73.  Review.

8.        Post, R.M., Weiss, R.B., Clark,M., Chuang, De-maw, Hough, Christopher and

Li, H.: Lithium, Carbamazepine, and Valproate in Affective Illness: Biochemical and Neurobiological Mechanisms. Biopolar Medications, Mechanisms of Action. Chapter 10, 219-248, 1999.

9.        Weiss, S.R.B., Li, H., Sitcoske-OShea, M. and Post, R.M.: Amygdala plasticity: the neurobiological implications of kindling. The Amygdala, second edition, Oxford University, chapter 4, 155- 194, 2000.

10.       Li, H. and Henry, J.L.: Inhibitory effects of adenosine on interneuron and interneuronal synaptic  transmission in rat hippocampus in vitro. European Journal of Pharmacology, 407(3): 237-44. 2000.

11.     Li, H. and Henry, J.L.: Adenosine receptor blockade reveals NMDA receptor- and voltage-sensitive dendritic spikes in rat hippocampal CA1 pyramidal cells in vitro. Neuroscience, 100(1): 21-31, 2000.

12.     Rogawski, M., Hurzman, P., Yamaguchi, S. and Li, H.: Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse. Neuropharmacology, 40(1): 28 35, 2001.

13.     Aroniadou-Anderjaska, V., Post, R. M., Rogawski, M. A. and Li, H.: Input-specific LTP and depotentiation in basolateral amygdala.  NeuroReport 12: 635-640, 2001.

14.    Li, H., Chen, A., Xing, G., Wei, M. and Rogawski, M.A.: Kainate Receptor Mediated Heterosynaptic     Facilitation in the Amygdala. Nature Neuroscience, 4(6): 612-620, 2001.

15.      Braga, M.F.M., Aroniadou-Anderjaska, V., Post, R.M. and Li, H.: 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, 2002.

16.    Rogawski, M.A., Gryder, D., Castanada, D. Yonekawa, W. and Li, H.: Kainate receptor mediated long-  term plasticity, seizures and epileptogenesis in the amygdala. New York Academy of Sciences, 985, 150-162, 2003.

17.    Braga, M. F., Aroniadou-Anderjaska, V., Xie, J, and Li, H. Bidirectional modulation of GABA release by presynaptic glutamate 5 kaiante receptors in the basolateral amygdala. Journal of Neuroscience. 23(1), 442-452. 2003.

18.       Chen, A., Hough, C.J. and Li, H. 5-HT2 Receptor activation facilitates synaptic plasticity via NMDA-Mediated mechanism in the basolateral amygdala. Neuroscience, 119, 53-63, 2003.

19.     Braga, M. F., Aroniadou-Anderjaska, V., Manion, S.T., Hough, C.J., and Li, H.  Stress impairs 1Adrenoceptor-mediated noradrenergic facilitation of GABAergic transmission in the basolateral amygdala.  Neuropsychopharmacology. 29,45- 58, 2004

20.      Braga, M., Aroniadou-Anderjaska, V. and Li, H. : The physiological role of GluR5 kainate     receptors in   neuronal excitability and neuroplasticity in the rat amygdala. An invited review paper for Molecular  Neurobiology 30(2):127-141, 2004

21.     Osuch E, Ursano R, Li H, Webster M, Hough C, Fullerton C, Leskin G. Brain environment interactions: stress, posttraumatic stress disorder, and the need for a postmortem brain collection. Psychiatry. 2004 Winter;67(4):353-83.    

22.       Zhang, ZJ, Jiang XL, Zhang SE, Hough, CJ, Li, H., Chen, JG, Zhen, XCh: The paradoxical  effects of SKF83959, a novel dopamine D1-like receptor agonist, in the rat acoustic reflex paradigm. Neuroscience Letters (382:134-138. 2005)

23.         Jiang, X.L., Chen A.Q. and Li, H.: Histaminergic Modulation of Excitatory Synaptic Transmission in the Rat Basolateral Amygdala. Neuroscience (131(3), 609: 2005)

24.         Zhang, L., Zhou, R., Xing, G., Hough, C.J. Li, H.: Identification of gene markers based on well validated and subcategorized stressed animals for potential clinical  applications in PTSD. Medical Hypotheses. In press, 2006 

25.          Zhang, L., Zhou, R., Li, X.X., Li, H.: Stress-induced change of mitochondria membrane potential regulated by genomic and nongenomic GR signaling: a possible mechanism for hippocampus atrophy in PTSD Medical Hypotheses, In press, 2006

Profile

Dr. Ann Marini

Associate Professor and has been a member of the faculty of the Uniformed Services University since 1994. She holds a secondary appointment in the Department of Neuroscience. Dr Marini earned both her Ph.D. degree from the Department of Biochemistry, 1978, and her medical degree from the Georgetown School of Medicine in 1980. She completed a residencies in medicine at UMASS Worcester, Massachusetts; 1980-1983; and in Neurology at Albert Einstein College of Medicine, Bronx, New York, 1983-1986 . She was a Senior Staff Fellow at NINDS/NIMH, 1986-1993. She was assigned to the Department of Neurology, Department of Veterans Affairs, Washington, D.C. from 1993-1994. She currently serves as Director of the Neurology Basic Science Research Division. Research interests: Mechanisms of Neuronal Cell Death and Neuronal Intrinsic Survival Pathways.

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. His laboratory is interested in understanding the mechanisms of cell response to stress and in the development of pharmacological therapies that may reduce the functional consequences of brain injury.

Contact:
Dept. of Anatomy, Physiology & Genetics
Uniformed Services University of the Health Sciences
4301 Jones Bridge Road
Bethesda, MD 20814
 

• University of Montana, 1971; Michigan State University, 1976

More than half of all known neuroendocrine peptides are alpha amidated and in nearly all cases, this structural feature is essential for receptor recognition and signal transduction. Alpha Amidation is a terminal modification in peptide biosynthesis and can itself be rate limiting in the overall bioactivation of peptide messengers. Thus, regulation of alpha amidation has importance to the vital roles of alpha amidated peptides in intercellular communication including control of brain, pituitary, pancreatic and gastrointestinal functions. A major objective of the research is to define the mechanisms that control the activity of alpha amidation by directly regulating the enzyme involved. Understanding the physiologic regulation of alpha amidation, and the basis for its control by pharmacologic treatments, should enable new approaches for inquiry into the role of peptide alpha amidation in health, disease and one's response to therapeutic interventions.

• Kerala University, 1971; Indian Institute of Science, 1977

Pathogenesis of Canavan disease and its treatment. Canavan disease is a neurodegenerative disorder caused by mutations in the enzyme aspartoacylase that degrade N-acetylaspartate into acetate and aspartate. Currently, no treatment is available for Canavan disease. Efforts are focused on a) developing an animal model for Canavan disease by knocking out aspartoacylase gene in the mouse and b) testing acetate supplementation as a therapy.

Functional roles of N-acetylaspartate and N-acetylaspartylglutamate in the nervous system. Current efforts involve cloning of the gene for aspartate N-acetyltransferase, a nervous system specific enzyme involved in the biosynthesis of N-acetylaspartate and N-acetylaspartylglutamate. Subsequent efforts would involve making a gene knockout system to study the functional roles.

Melatonin and circadian rhythms. Current efforts are focussed on structural studies of serotonin N-acetyltransferase, the enzyme responsible for the circadian regulation of melatonin production. Long term goals include development of inhibitors of the enzyme for use as drugs to control serotonin and melatonin levels in human.

Physiological and pathological roles of kynurenine pathway activation in the neuroimmune system. Earlier studies from this laboratory have shown that macrophages and dendritic cells are the primary sites of kynurenine pathway activation that occurs in response immune stimulations. Recent studies have shown that this is an important mechanism by which macrophages and dendritic cells regulate T-cell functions. Current efforts are focussed on identifying the genes that are regulated in response to kynurenine pathway activation in mixed cell cultures of T cells and macrophages using DNA microarray techniques.

Profile

Ph.D., Neurophysiology, Tarbiat Modarres University, Tehran, Iran, 2003
Postdoctoral, Neuroscience, Brown University

Synaptic plasticity of the Reward Pathway

Since the discovery of synaptic plasticity as the cellular correlate of learning and memory, strong overlaps between neural and cellular substrates of learning, drug addiction and stress-related disorders have been recognized. Yet it remains a major challenge to identify the neural circuits and synaptic mechanisms contributing to abnormalities in dopamine signaling induced by addictive drugs and adverse early life experiences. The major focus of my laboratory is the elucidation of synaptic mechanisms underlying reward learning, drug addiction and neuropsychiatric disorders such as depression, with particular emphasis on the midbrain dopamine system originating from the ventral tegmental area (VTA) and its control by the lateral habenula (LHb). Research in our laboratory also explores effects of severe early life stress on synaptic transmission and plasticity of distinct VTA dopamine circuits to identify the neural circuits and molecular mechanisms contributing to abnormalities in dopamine signaling induced by adverse early life experiences. To achieve these goals, we use a combination of immunohistochemical, biochemical, epigenetic, electrophysiological and behavioral techniques. We expect that identifying novel epigenetic mechanisms in the regulation of synaptic plasticity and memory formation in midbrain dopamine circuits will point to new directions in pharmacotherapy for drug addiction and stress-related disorders.

Selected Publications

Authement M.E., Kodangattil J.N.,Gouty,S., Rusnak, M., Symes A.J., Cox B.M., and Nugent F.S., Histone deacetylase inhibition rescues maternal deprivation-induced GABAergic metaplasticity through restoration of AKAP signaling, Neuron, 86: 1240–1252 (2015)

Kodangattil J.N., Dacher M.A., Authement, M.E. and Nugent F.S., Spike timing-dependent plasticity at GABAergic synapses in the Ventral tegmental area. Journal of Physiology, 591.19: 4699-710 (2013)

Dacher, M. A., Gouty, S., Dash, S., Cox, B.M., and Nugent, F.S., A-kinase anchoring protein-calcineurin signaling in long-term depression of GABAergic synapses, Journal of Neuroscience, 33:2650-60 (2013)

Nugent, F.S., Penick, E.C., Kauer, J.A., Opiates block long-term potentiation of GABAergic synapses. Nature, 466: 1086-1095 (2007)

Postdoctoral Fellows: Dr. Haifa Kassis and Dr. Ludovic Langlois

Graduate Students: Michael Authement and Ryan Shepard

Lab Alumni: Dr. Matthieu Dacher (Université Pierre et Marie Curie, France), Dr. Jayaraj N. Kodangattil and Steven Dash

Profile

Our laboratory focuses attention on the molecular basis of various secretory processes whose dysfunction results in human disease. Neurotransmitter and neurohormone release occur from nerve terminals, endocrine, and exocrine cells by a fusion mechanism sensitive to ionic calcium, GTP, protein kinase C, and other kinases. Two disease-related applications of these interests have been pursued: Synexin (annexin VII, ANX7) is a Ca2+ channel protein and newly identified member of the GTPase Superfamily which uniquely fuses membranes, and is regulated by Ca2+, GTP and various protein kinases. It is also a newly identified component of the "fusion machine" which is believed to mediate docking and fusion during exocytotic secretion. Defects in these processes have been implicated in the pathologies of hypertension and diabetes, among others. These exciting results have prompted Dr. Pollard to investigate how the protein works in vivo using methods of site directed mutagenesis, prokaryotic and eukaryotic mutant protein expression, adenovirus transduction, and transgenic and knockout technologies.

We have also applied our insights from synexin studies to the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), which is important for exocrine secretory processes. This protein, which is defective in the most common genetic disease, cystic fibrosis (CF), has nucleotide binding domains which are highly homologous with the annexin gene family. Like annexins, these domains interact specifically with the membrane, and mutations known to cause CF disrupt these interactions. Molecular analysis of the structure of these domains have led to our development of compounds which are currently being tested clinically for treatment of cystic fibrosis. In addition to conventional molecular methods employed for this study, our other approaches include fluorescence spectroscopy, confocal microscopy, lipid biochemistry, and organic synthesis.

• Postdoctoral, National Institute of Environmental Health Sciences
• Ph.D., University of Massachusetts, Amherst, 2004
• B.A., University of Massachusetts, Amherst, 1999

Research Description

Research in our laboratory focuses on the interface between the morphology and function of the largest organelle in the cell, the endoplasmic reticulum (ER). The ER forms an elaborate, stunningly dynamic network of flat sheets and thin, lattice-like tubules throughout the cytoplasm in animal cells. Defects in ER morphogenesis underlie several debilitating neurodegenerative disorders such as Hereditary Spastic Paraplegia, illustrating the essential role of proper ER morphology in human physiology. However, mechanisms by which specific features of ER morphology and dynamics influence cellular and tissue physiology are still poorly understood. We address this fundamental problem by employing a number of powerful experimental systems, including Drosophila genetics and phenotypic analysis, live microscopy of human and Drosophila cells and tissues, and biochemical assays. We are particularly interested in understanding the functional interactions of the ER with the microtubule cytoskeleton, and are currently pursuing this topic through two related projects:

ER-microtubule interactions during cell division

As for most organelles, cells cannot generate the ER de novo; instead, they must inherit it during the process of cell division. This is not unlike the inheritance and partitioning of chromosomal DNA; however, unlike DNA, the mechanisms that regulate ER distribution and partitioning during cell division are largely unknown. We recently demonstrated that association of the ER with astral microtubules of the mitotic spindle is a conserved mechanism that regulates ER partitioning during both symmetric and asymmetric cell division. Our goal now is to identify the specific molecules that link the ER with spindle microtubules, and using Drosophila as an animal model, to further define the physiological role of mitotic ER partitioning in development and tissue homeostasis.

ER transport in neurons

Neurons are one of the most highly polarized cell types in the body, and the functional and molecular properties of dendrites, the receiving ends of neurons, are necessarily different from those in axons, the transmitting ends. Consistent with this, the organellar composition of axons and dendrites is differentially regulated through highly specific mechanisms. We are currently investigating cytoskeleton-based mechanisms that regulate the transport and functions of the ER in different neuronal compartments. This work is essential to the prevention and treatment of neurodegenerative diseases, many of which are primarily caused by defects in organelle trafficking and homeostasis. This will also facilitate a greater understanding of neuronal response and repair following damage, such as traumatic brain injury (TBI).

Profile

• Ph.D. Biochemistry, University College London, UK
• Postdoctoral Fellowship: Neurology, Massachusetts General Hospital/ Harvard Medical School

Research Interests:

Our lab aims to understand the mechanisms through which the brain responds to traumatic injury and more specifically to delineate the pathways through which detrimental neuroinflammatory cascades can be altered to enhance recovery after injury. The initial lesion can produce significant tissue damage and breakdown of the blood brain barrier. These immediate effects lead to activation of many secondary cascades involving interplay between endogenous surviving neurons and glia, and infiltrating cells and molecules from the bloodstream. Injury therefore leads to acute neuroinflammatory cascades, and also to more chronic inflammatory effects.  Indeed, activated microglia have been documented in postmortem brains many years after the initial insult. Our lab focuses on understanding the molecular signaling cascades that occur after injury in addition to testing potential therapeutics to enhance recovery from injury. We currently utilize several different rodent models of traumatic brain injury (TBI), with assays ranging from behavioral through molecular to understand the complex interactions that occur after injury, and to determine how manipulations may impact on functional recovery. We also utilize primary cell cultures to tease apart the molecular signaling pathways that contribute to inflammation after injury.

TGF-β signaling after injury

TGF-β is an injury induced cytokine that has complex roles in the central nervous system. After brain injury TGF-β can promote astrogliosis and enhance the deposition of molecules inhibitory to regeneration in the glial scar. Yet TGF-β is also neuroprotective indicating the sometimes conflicting roles of this cytokine. We have shown that after a penetrating brain injury mice that lack expression of the TGF-β signaling molecule Smad3, form a glial scar more quickly, with a smaller scar, than wild type mice. However, we also found that Smad3 null mice have more pronounced neuronal loss after injury. Thus, global interference with TGF-β signaling is not a desirable therapeutic option. Further, TGF-β is anti-inflammatory in some contexts – so chronic repression of TGF-β signaling pathways may enhance inflammation. In primary microglial cultures we have shown that inflammatory pathways downregulate TGF-β receptor expression, allowing for prolonged enhancement of the inflammatory activated state.

Angiotensin receptor blockers as potential therapeutics for TBI

Angiotensin receptor blockers (ARBs) are widely used FDA-approved anti-hypertension drugs with a favorable side effect profile that have been used as a mechanism for reducing the amount of TGF-β signaling in several different organ systems. In the CNS, ARBs have also been shown to be neuroprotective, anti-inflammatory and protective of the cerebral blood flow (CBF). The brain possesses its own renin angiotensin system, with many different components of the system expressed in the different cell types in the brain. However, in addition to acting as antagonists at the Angiotensin II receptor 1 (AT1R) some ARBs also possess potent PPARγ agonist activity that enhances their anti-inflammatory action. We have demonstrated that the ARB candesartan, lessens inflammation, reduces lesion volume, limits glial reactivity, increases neuronal survival and improves motor and cognitive recovery up to 28 days after injury. These beneficial effects are seen when low-dose candesartan is administered up to 6 hours after injury, a clinically acceptable therapeutic window. Our data suggest that both AT1 receptor antagonism and PPARγ agonism contribute to the efficacy of ARB treatment after TBI and it is this multimodal action by a single drug that makes it a strong candidate for TBI clinical trials. We are pursuing translational studies for candesartan for brain injury in addition to investigating the consequences of TBI on the endogenous renin-angiotensin system in the brain.

Profile

Director, Center for the Study of Traumatic Stress
Professor of Psychiatry and Neuroscience, Chair Department of Psychiatry

Robert J. Ursano, M.D., is Professor of Psychiatry and Neuroscience and Chairman of the Department of Psychiatry at the Uniformed Services University of the Health Sciences, Bethesda, Maryland. He is founding Director of the internationally recognized Center for the Study of Traumatic Stress which has more than $20 million dollars in research funding. In addition, Dr. Ursano is Editor of Psychiatry, the distinguished journal of interpersonal and biological processes, founded by Harry Stack Sullivan. Dr Ursano completed twenty years service in USAF medical corps and retired as Colonel in 1991.

Dr. Ursano was educated at the University of Notre Dame and Yale University School of Medicine and did his psychiatric training at Wilford Hall USAF Medical Center and Yale University. Dr. Ursano graduated from the Washington Psychoanalytic Institute in 1986 and is a member of the teaching faculty of the Institute. Dr. Ursano served as the Department of Defense representative to the National Advisory Mental Health Council of the National Institute of Mental Health and is a past member of the Veterans Affairs Mental Health Study Section and the National Institute of Mental Health Rapid Trauma and Disaster Grant Review Section. He is a Distinguished Life Fellow in the American Psychiatric Association. He is a Fellow of the American College of Psychiatrists, and of the American College of Psychoanalysts and is listed in Who's Who in America and Who's Who in Medicine and Health Care.

Dr. Ursano was the first Chairman of the American Psychiatric Association's Committee on Psychiatric Dimensions of Disaster. Through his work with the Committee, the American Psychiatric Association established a collaborative relationship with the Red Cross, the Bruno Lima Award, to recognize contributors to psychiatric care in times of disaster, and the Eric Lindemann Grant to support disaster services. This work greatly aided the integration of psychiatry and public health in times of disaster and terrorism.

His continued service and leadership in committee activities has been instrumental to the development of the APA's disaster psychiatry training program, and to the development and widespread international dissemination of psychosocial support training for emergency responders after the December, 2007 Southeast Asian Tsunami and in the immediate and extended aftermath of Hurricane Katrina. His Center's training and post-disaster health surveillance materials are currently being translated into Chinese to assist in the psychosocial response to recent earthquake victims.

Dr. Ursano was an invited participant to the White House Mental Health Conference in 1999. He has received the Department of Defense Humanitarian Service Award and the highest award of the International Traumatic Stress Society, The Lifetime Achievement Award, for "outstanding and fundamental contributions to understanding traumatic stress." He is the recipient of the William C. Porter Award from the Association of Military Surgeons of the United States, and a frequent advisor on issues surrounding psychological response to trauma to the highest levels of the US Government and specifically to the Department of Defense leadership. As a result of his widely recognized leadership in trauma and disaster preparedness and response, his was one of the first Centers recognized as a partnering center with the newly established Department of Defense National Center of Excellence for Psychological Health and Traumatic Brain Injury.

Dr. Ursano has served as a member of the Advisory Board of the National Partnership for Workplace Mental Health (American Psychiatric Association); the White Paper Panel on Bioterrorism and Health Care, Joint Commission on Accreditation of Health Care Organizations; the Scientific Advisory Board on Bioterrorism of SAMSHA (HHS), Center for Mental Health Services; the Advisory Board of the Center on Terrorism of the University of Oklahoma School of Medicine; the National Academies of Science, Institute of Medicine, Committee on Psychological Responses to Terrorism, Committee on PTSD and Compensation and the Committee on Nuclear Preparedness; and the National Institute of Mental Health Task Force on Mental Health Surveillance After Terrorist Attack. In addition he is a member of scientific advisory boards to the for HHS and the CDC.

Dr. Ursano has over 300 publications. He is co-author or editor of seven books. His publications include the internationally recognized volume Individual and Community Responses to Trauma and Disaster: The Structure of Human Chaos. (Cambridge University Press.) His 2007 Textbook of Disaster Psychiatry (Cambridge University Press) is the most comprehensive treatment of the subject to date. His books on psychotherapy have been translated and published in Russia, Turkey, China and Japan.

He is widely published in the areas of Post-Traumatic Stress Disorder and the psychological effects of terrorism, bioterrorism, traumatic events and disasters and combat. He and his team have served as consultants and completed studies on numerous disasters, disaster rescue workers, motor vehicle accident victims, family violence, and Viet Nam, Desert Storm and Gulf War veterans. His research group completed the follow-up studies of the USAF Vietnam era prisoners of war, identifying the critical role of degree of exposure to outcome, resiliency, and the development of psychiatric disease in those with no known risk factors. He was part of the design of the repatriation of the Desert Storm prisoners of war. His work on disaster first responders is noted for the focus on public health needs. His group has studied the psychiatric responses of individuals to disasters and to small-scale traumatic events including motor vehicle collisions in order to better understand the human trauma response and its mechanisms of disease and recovery. His group was the first to identify increased rates of child neglect during the Iraq war deployments.

Dr. Ursano was instrumental in the efforts of a group of twenty of the world's most renowned experts in disaster mental health in an exhaustive review of the empirical evidence surrounding psychosocial intervention after disaster. This workgroup recently published "Five Essential Elements of Immediate and Mid-Term Mass Trauma Intervention: Empirical Evidence." This visionary multi-disciplinary effort synthesizes the wealth of international disaster mental health/public health intervention experience and study into basic principles which will inform subsequent development of disaster preparedness and response at the community, state, national, and international levels for the foreseeable future.

Dr. Ursano has provided input and leadership into the development and dissemination of clinical best practices for the treatment of Acute Stress Disorder and Posttraumatic Stress Disorder. He chaired the American Psychiatric Association?s task force on Practice Guidelines for the Treatment of Acute Stress Disorder and Post-Traumatic Stress Disorder. This led to 2004 publication of the most comprehensive review and synthesis of the evidence basis for pharmacological and psychotherapeutic treatment of these disorders in the first edition of American Psychiatric Association?s Practice Guideline for the treatment of these illnesses. He has subsequently served in leadership positions on Institute of Medicine committees and task forces requested to develop policy guidance for disability evaluations related to PTSD and to review and synthesize treatment evidence developed since the publication of the APA guidelines.

Dr. Ursano and his group are at the forefront of public health policy planning for terrorism, and bioterrorism in particular and for the effects of war and deployment on military members and their families. Their work has been widely cited in government planning and Institute of Medicine, National Academies of Sciences reports addressing these issues. He was a national consultant for planning clinical care responses and research programs following the September 11th terrorist attacks, providing consultation to New York State Governor's Office, New York City Mayor's Office, Department of HHS, National Capital response teams and the Department of Defense Pentagon response groups. His group developed educational materials that were some of the most widely disseminated throughout the nation to assist populations exposed to the September 11 attack. Dr Ursano is on the Natonal Bioscience Advisory Board subcommittee for Mental Health to advise the Secretary of Health and Human Services on needs for mental health in disaster. Dr Ursano is also a member of the Scientific Advisory Board of the Coordinating Office for Terrorism Preparedness and Emergency Response of the Centers for Disease Control and Prevention advising the director on preparedness and response for terrorism.

In addition to cutting edge public health policy and disaster response planning, Dr. Ursano continues to spearhead major advances in understanding the neurobiological processes of traumatic stress response. His efforts have led to the development of a first of its kind collaborative endeavor with Academic Centers including Yale University, Stanford University, the University of Washington, various Veteran?s Affairs Hospitals and the VA's National Center for PTSD to identify, collect, process, and distribute neural tissue for pathological, microcellular, and genetic studies of PTSD. Stemming from this ongoing collaboration Dr. Ursano and colleagues recently reported their identification of a potential genetic biomarker for PTSD, p11. This critical pioneering report of pilot data is the first of its kind in the scientific literature, and will certainly promote and inspire further research in this direction.

Dr. Ursano's research has been funded by the National Institute of Mental Health, SAMSHA, CDC, NIOSH, the Sloan Foundation, the United States Army, the United States Air Force, and other national foundations and agencies.

Molecular neuroendocrine regulation of reproductive function Information

B.S. Zoology, The University of Texas at Austin
Ph.D. Reproductive Physiology, Texas A&M University
Post Doctoral Training Developmental Neuroendocrinology, Columbia University
Molecular Neuroendocrinology, Mount Sinai School of Medicine
Molecular Neueroendocrinology

The laboratory focuses on the molecular and developmental regulation of neuroendocrine systems. Our focus are, gonadotropin-releasing hormone (GnRH) peptides and ovarian steroids.

In the brain, neurons that synthesize GnRH have a scattered distribution along the basal forebrain region with the highest numbers located around the organum vasculosum of the lamina terminalis (OVLT) in many animal species. The approximately 1000 GnRH neurons extend their axons to the median eminence of the hypothalamus where they terminate to form the final common pathway for the regulation of reproductive function. During development, GnRH neurons are "born" in the olfactory placode and begin their migration into the brain along the vomeronasal nerve. Recently, other forms of GnRH's have been cloned in the brain and in peripheral tissues. In addition to their ability to regulate reproductive function via its action at the pituitary, GnRH is known to have extrapituitary actions. Agonists and antagonists of GnRH are some of the most commonly used drugs. The discovery of these multiple forms of GnRH's and their respective receptors may alter the way we design the next generation GnRH agonists and antagonists to treat major clinical symptoms among women. The questions we are asking in the lab are: What are the molecular and biochemical mechanisms involved in the developmental, tissue-specific, hormonal, and neurotransmitter regulation of GnRH's gene expression and neuron-specific gene expression? What is the nature of the clock that regulates the pulsatile secretion of GnRH? How does GnRH regulate behavior?

Likewise, the recent discoveries of multiple forms of steroid hormone receptors and the lack of specificity in agonist or antagonist action have resulted in controversies in their clinical applications. The new generations of SERMS (selective estrogen receptor modulators), for example, have allowed us to better understand mechanisms of action. Our laboratory focuses here on how steroid hormones regulate behaviors such as motivation and anxiety. A major focus will be to determine the underlying role of steroid hormones in post-traumatic stress syndrome.

• Binzhou Medical School, China, M.D., 1985
• Hebrew University, Israel Ph.D., 1998

The long-term goal of my laboratory is to study the cellular and molecular mechanisms of glial and neuronal toxicity and the pathogenesis of neurodegenerative diseases.

Brain injury is often accompanied with inflammation. Nitric oxide and its reaction product with superoxide, peroxynitrite, are the major toxic species released from the reactive astrocytes and microglia. We are now particularly interested in elucidating the signaling pathways of peroxynitrite toxicity to oligodendrocytes (OLs) using primary cultures from rat and mice brain. Our previous work has suggested that activation of arachidonic acid metabolism plays an important role in the toxicity of peroxynitrite to premyelinating OLs (preOLs) and to mature OLs that produce myelin basic protein. However, distinct cell death pathways are involved in these two cell types. We are now investigating these cell death mechanisms using pharmacological, biochemical and molecular approaches in culture, and testing whether these signaling molecules are critical in the animal models of cerebral palsy and multiple sclerosis, the two major demyelinating diseases found in premature infants and young adults, respectively.

Another area of the research is to study the mechanisms of motor neuron injury in amyotrophic lateral sclerosis (ALS). Although motor neuron dysfunction and degeneration are hallmarks of ALS, recent evidence indicates the toxicity of the mutants of Cu/Zn superoxide dismutase (SOD1), which cause one form of familial ALS, is non-cell autonomous, suggesting that the interplay between neurons and other cell types might play an important role in the pathogenesis of ALS. We will use biochemical, molecular and proteomic approaches to uncover the specific cellular components that contribute to the toxic effects of astrocytes or microglia and the increased vulnerability of motor neurons to the toxic stimuli.