Faculty Research Interests

The University of Texas at Austin

David P. Crews, Ph.D.
Section of Integrative Biology
(512) 471-1113
(512) 471-6078 fax

My research focuses on problems in reproductive biology, principally on the development and function of sex and individual differences. All of our research employs a comparative, interdisciplinary approach that combines and integrates the molecular, cellular, physiological, morphological, organismal, ecological, and evolutionary levels of analysis. Our research is conducted both in the laboratory and in the field to illustrate how the causal mechanisms and functional outcomes of reproductive processes operate at each level of biological organization while, at the same time, illuminating the relations among the levels.

Yvon Delville, Ph.D.
Department of Psychology
(512) 232-5731

Neuroendocrinology of social behavior and stress during puberty

Michael Domjan, Ph.D.
Department of Psychology
Imaging Research Center
(512)  471-7702

During most of my career, I have been studying behavioral mechanisms of learning, primarily in animals. I have been interested in adaptive specializations and functional approaches to learning. I first studied these issues in taste aversion learning and then developed an extensive program of work to study sexual conditioning. That research involved exploring conventional learning phenomena in the sexual behavior system in an effort to evaluate the generality of learning mechanisms. It also involved exploring ways in which learning is involved in how animals respond to species typical cues or sign stimuli. This latter line of work is revealing how learning can be involved in ecologically relevant situations.

From 1999 to 2005 I served as Chair of the Psychology Department and was then appointed Director of the newly established Imaging Research Center (IRC) at the University. In addition to taking care of administrative aspects of the

IRC, I am learning about Magnetic Resonance Imaging (MRI) and hope to conduct experiments on the neural mechanisms of learning in people using MRI.

Rueben Gonzales, Ph.D.
Department of Pharmacology, College of Pharmacy
(512) 471-5192
(512) 475-6088 fax

The overall goal is to understand the neurochemical basis for ethanol drinking behavior. Since the brain controls behavior, and neurons are the basic functional unit of the brain, it follows that neuronal activity underlies ethanol drinking behavior. Neuronal activity is controlled in part by the chemical microenvironment, so a major objective of the lab is to characterize the chemical changes in the brain that may underlie alcohol drinking. The research entails a combination of behavioral and chemical techniques.

Current interests include the effects of ethanol on basic dopaminergic neuronal activity in vivo, and the involvement of dopamine and glutamate in ethanol self-administration behavior. More recent interests include the physical characterization and theoretical description of diffusion behavior of solutes during in vivo microdialysis. Two new projects have been undertaken in the lab in the last few years. We have begun development of capillary electrophoresis with laser induced fluorescence detection, a new analytical system for detection of neurotransmitters in dialysates. This new analytical technique will enable much faster sampling and analysis of neurotransmitters to allow better correlations between neurochemical activity and behavior. Secondly, we have adapted the microdialysis technique for use in mice. Using this adaptation has allowed us to expand our studies using genetic models such as null mutant mice. We are currently studying the role of the mu opiate receptor and the dopamine D2 receptor in the regulation of dopamine release by ethanol.

Francisco Gonzalez-Lima, Ph.D.
Department of Psychology
471-5895, 475-8497
471-1073 fax

My laboratory is a pioneer of new metabolic and computational approaches of brain research, including learning, memory, neuroprotection, and the neural mechanisms of behavior. Our research orchestrates tools from neuroanatomy, neurophysiology, biochemistry, pharmacology and toxicology, in combination with computational and behavioral analyses. Our group is highly experienced in the behavioral testing of laboratory rodents and the examination of the underlying neural mechanisms.

Our lab lead neuroimaging research of behavioral and learning functions using fluorodeoxyglucose autoradiography. We developed new brain metabolic mapping methods such as quantitative histochemistry of cytochrome oxidase and were the pioneer investigators studying its application in numerous species, including humans. We carry out accelerating integrative neuroscience studies using genetic animal models, such as rodent models of learned helplessness and Alzheimer’s disease. Our research is revitalizing the foundations of neuroscience leading to a new understanding of neural metabolic energy and the therapeutics of neurobehavioral disorders.

Daniel Johnston, Ph.D.
Center for Learning & Memory
Austin, TX 78712

Research in my laboratory is primarily directed towards understanding the cellular and molecular mechanisms of synaptic integration and long-term plasticity of neurons in the medial temporal lobe. We have focused our attention on the hippocampus, subiculum, and entorhinal cortex, areas of the brain that play important roles in learning and memory. These regions are also of interest because they have a low seizure threshold and are implicated in several forms of human epilepsy. Our research uses quantitative electrophysiological, optical-imaging, and computer-modeling techniques.

We are investigating long-term synaptic potentiation and depression, forms of plasticity thought to underlie aspects of memory. This interest has led us to investigate the basic mechanisms of synaptic integration in the dendrites of the neurons in these regions. We have used fluorescence imaging techniques and dendritic patch-clamp recordings to identify the types of voltage-gated ion channels (Na+, K+, Ca+, and h channels) expressed in dendrites of hippocampal and entorhinal cortex pyramidal neurons. We have also begun to identify changes in the properties and expression levels of some of these channels accompanying synaptic potentiation and depression. These studies have suggested that plasticity of intrinsic excitability of neurons is an important component of learning and memory. Our computer modeling studies, which reconstruct the biophysical properties of these neurons based on our experimental data, complement this work. We hope that these investigations will enhance our understanding of the neuronal mechanisms of learning and memory and provide insight into the function of the hippocampus and neighboring cortex in the normal behaving animal as well as under disease states such as epilepsy.

Theresa Jones, Ph.D.http://www.utexas.edu/neuroscience
Department of Psychology
(512)  232-1814

Jones’ research is on neural plasticity across the lifespan and recovery from brain damage, including stroke.   One strategy for improving function in those surviving brain damage is to re-organize the brain so that lost function is circumvented by remaining neural circuitry.  Learning is accomplished by changes in neural circuitry in the brain, but after brain damage, these changes happen in a brain that is also responding and adapting to the degenerative and neurotoxic effects of damage.  The focus of Jones’ research is understanding how damage- and learning-induced brain changes interact to influence neural and glial plasticity and, ultimately, functional outcome.

Timothy J. Schallert, Ph.D.
Department of Psychology
(512) 471-6141
(512) 232-4335
lab website:  https://labs.la.utexas.edu/schallert/

Research in the Schallert lab includes behavioral and biological interventions targeting rat and mouse models of Parkinson’s disease, stroke, brain tumors, and related neurological disorders.  Other areas of investigation include neural mechanisms of learning and memory, drug addiction, aging and brain development.  New behavioral assessment techniques are used to address brain-behavior relationships.

The brain and spinal cord are vulnerable to traumatic injury, stroke, tumors and degenerative diseases, often with devastating functional impairments, but at no time in the history of medicine have scientists been as optimistic as they are now about treatment strategies. Understanding how the central nervous system responds to the loss of nerve cells, and how behavior can influence the mechanisms of brain repair, is a major focus of our research.

We develop rat and mouse models of neurological disorders and strive to improve upon existing models. We have a multidisciplinary approach, with extensive collaborative arrangements with experts in other labs on campus, nationally and internationally. Collaborative research projects include searching for novel treatment interventions.

In Parkinson’s disease dopamine cells degenerate, eventually leading to severe impairments of movement. Using a new model of slow degeneration, we have investigated gene therapy, drugs and motor enrichment techniques that increase growth factors in the brain. These growth factors appear to keep the dopamine cells from dying, thereby preventing the behavioral dysfunction.

Whereas skilled motor activity protects neurons, behavioral inactivity is detrimental. In cerebral stroke, Parkinson’s disease, and other models of brain injury, physical activity and inactivity have only recently been recognized as highly influential. Behavior is often essential for cellular changes, synapse formation and neurogenesis. We look for sensitive periods after brain damage that provide unique opportunities to intervene beneficially.

We have helped to develop new models to investigate brain tumor interventions. Unlike other models used to examine anti-cancer treatments, our model includes a highly sensitive behavioral analysis of brain function and neural plasticity, which are often adversely affected by traditional anti-cancer interventions. The hope is to use this model to find treatments that can shrink brain tumors without disturbing mechanisms important to optimal brain function. We also want to understand the stealth nature of brain tumors. Tumor cells slowly activate key mechanisms of plasticity which hide their presence despite ever more extensive encroachment on critical brain tissue. In collaboration with investigators at the University of Michigan and Henry Ford Neuroscience Center, we have developed promising chemical interventions that, unlike traditional treatments, appear to stop mitotic activity in tumor cells implanted in the striatum of the brain, without interfering with mechanisms of recovery of function and with a beneficial impact on behavioral outcome due to a positive effect on remaining tissue.

Other research includes investigating neural mechanisms of learning and memory, drug and alcohol abuse, and brain deveopment/aging.

The University of Texas San Antonio

Edwin Barea-Rodriguez, Ph.D.
Department of Biology
210-458-5481 office
210-458-4271 lab
210-458-7498 fax

The major goal of my laboratory is to investigate if short-term dietary restriction started late in life affects learning and synaptic plasticity in aged rats.  Also I am interested in mentoring minority students, and in incorporating connectedness, communication, and inclusion into the learning process.

Brian Derrick, Ph.D.
Department of Neurobiology
(210) 458-5661
(210) 691-5658 fax

My research interest involves behavioral correlates of long-term potentiation, synaptic mechanisms regulating adult neurogenesis, neurocomputation at the dentate-CA3 interface, the contribution of striatal plasticity to drug dependence.

Joe Martinez, Ph.D.
Department of Biology
(210) 458-4279
(210) 458-7846 fax

My research interests lie in the neurobiology of learning and memory.  There a re currently four projects that focus on the mechanisms that underlie learning and memory processes in the mammalian brain.  In Project 1 we are performing in situhybridization to localize the expression of candidate learning and memory genes in the hippocampus following Morris Water Maze training and Long Term Potentiation (LTP).  In Project 2 we are examining how whole brain irradiation (WBI) disrupts hippocampus-dependent learning and memory and hippocampal morphology, as well as putative therapeutic mechanisms to ameliorate radiation-induced cognitive dysfunction.  In Project 3 we are selectively blocking hippocampal dopamine receptors to determine the role of dopamine receptor signaling in drug self-administration, and in Project 4 we are examining the involvement of protein synthesis in the acquisition and maintenance of hippocampal LTP.

University of Texas Health Science Center San Antonio

Jack L. Lancaster, Ph.D.
Research Imaging Center
(210) 567-8100
(210) 567-8152

My research interest focus on the extraction of information from medical images using the fundamental steps of image processing. I work with programmers and researchers to develop software not available commercially to enable the exploration of new biological and medical research questions using tomographic images (MRI, CT, PET, and SPECT). Medical imaging provides methods for macroscopic measurements of numerous parameters of interest including blood flow, diffusion coefficients, T1, T2, proton density, electrical activity, just to mention a few. The in vivo measurements associated with imaging research are bounded to a spatial resolution of about 1mm, a temporal resolution ranging from 1 msec to minutes, and contrast resolutions as low as 5%. However, special techniques can often be employed to extend these limits.

Current externally funded projects include the development of a probabilistic atlas for the human brain (NIH/NIMH), the human brain database BrainMap (NLM), Aiming theory and robotic positioning of transcranial magnetic stumulators for the brain (NIH/NIMH), and a collaboration for the analysis of MRI parametric images for subjects with 18q- Syndrome (NIH). We’ve established a large database of findings from functional brain imaging studies and provide access to this data using the WWW (http://ric.uthscsa.edu/services).

A number of new projects are underway including development of multifeature segmentation with fuzzy classifiers, high speed calculation of MRI parametric images (T1, T2, and proton density), and high-speed 3-D deformation of brain images to match a standard brain atlas. I supervise Ph.D. students in the Radiological Sciences graduate program that are seeking to discover new methods to measure and model biological systems.

Peter T. Fox, M.D.
Research Imaging Center
(210) 567-8150
(210) 567-8152

David Glahn, Ph.D.
Director of Neuroimaging Core in Psychiatry,
Department of Psychiatry and Research Imaging Center
Voice (210) 567-5508
Fax (210) 567-1291

Neuroimaging – As director of the Psychiatric Neuroimaging Core (PNC), I am dedicated to establishing an environment that will foster collaborative functional, structural and physiologic neuroimaging research within the department and throughout the medical school. The aims of the PNC are (1) to promote research with existing faculty and to aid in the recruitment of new imaging faculty, (2) to provide formal and informal educational opportunities for faculty, post-doctoral fellows and residents in imaging methods, experimental design and data analysis techniques and (3) to design and maintain a state of the art image analysis laboratory. To facilitate these goals, I developed a 2 credit course on functional MRI open to graduate and post-graduate students and faculty members. The course will be listed in the graduate school for Radiological Sciences.

Neuropsychology – To facilitate research with various local, national and international collaborators and as a teaching tool for post-doctoral fellow within the department of psychiatry, I developed the South Texas Assessment of Neurocognition (STAN), a partially computerized battery of neuropsychological tests sensitive to the cognitive impairments found in schizophrenia and bipolar disorder. The STAN integrates standard clinical and experimental measures to assess both broad and narrow cognitive abilities and automatically enters this data into an ACCESS database. Tests included in this battery were selected based on (1) evidence of significant heritability, (2) evidence for sensitivity to mental illnesses and (3) minimizing the effects of language (culture) or the availability of parallel English and Spanish forms. The STAN taps a wide range of cognitive domains, including general intellectual functioning, sensory-motor and processing speed, attention, executive functioning, working memory, long-term memory, language and social cognition. I have conducted numerous 3-day seminars with the STAN to provide a basis in neuropsychological theory and practice for healthy care providers and biomedical researchers without exposures to these concepts. These seminars have been conducted in San Antonio, throughout the state of Texas, nationally and internationally.

Psychiatric Genetics – My research in psychiatric genetics focuses on defining quantitative measures that can be used for identifying genes associated with mental illness or in determining individuals at risk for these illnesses. To date, my research has largely focused on developing neuropsychological and neuroimaging indices sensitive to genetic liability for schizophrenia and affective disorders (bipolar disorder and unipolar depression). In a parallel effort, my laboratory is engaged in the search for genes influencing neuroanatomic, neurophysiological and neurocognitive endophenotypes for various neurological and psychiatric disorders in a sample of 1,000 randomly ascertained Mexican American individuals.

Imaging Genomics – The goals of the Imaging Genomics Program (IGP) are to discover genes that affect brain structure and function, utilize functional genomic or proteomics methods to elucidate biological mechanisms leading to variation in gross neruoanatomic or neurophysiological indices, and develop analytic tools to readily integrate neuroimaging and genetic data.  As IGP director, I collaborate with John Blangero, Peter Fox and others to collect large-scale imaging data sets from human or non-human primates that include DNA, cognitive-behavioral markers, and, often, quantitative leukocyte-derived gene expression measures. The creation of algorithms and software specifically designed to facilitate the analyses of these data constitutes a significant scientific endeavor and will provide ample educational opportunities for post-doctoral fellows, residents and graduate students.

Julie Hensler, Ph.D.
Department of Pharmacology
(210) 567-4200
(210) 567-4300 fax

I am interested in the cellular and molecular mechanisms by which neurotransmitter receptor systems compensate or change in disease states, or in response to repeated drug treatment. Because the treatment of many psychiatric disorders involves long-term pharmacological intervention, compensatory changes in the sensitivity of central receptor systems may be involved in the mechanism by which drugs produce their therapeutic or side effects.  My research group has focused primarily on the regulation of serotonin receptor function. The serotonergic system in brain has been implicated in substance abuse and addiction, as well as many psychiatric disorders.  We have taken both in vivo and in vitro approaches to examine the processes underlying the regulation of serotonin receptor function and expression.

Recently, my research team has begun studies to identify differences in serotonin receptors and in the serotonin transporter in genetically modified mice, which are deficient in brain derived neurotrophic factor (BDNF). BDNF has functional influences on neurons, plays a fundamental role in promoting the structural plasticity of serotonergic, noradrenergic and dopaminergic neurons in the adult brain, and may be involved in the pathophysiology of stress-related mood disorders, such as anxiety or major depression. We have found that these BDNF-deficient mice are vulnerable to stress, and exhibit depressive-like behaviors following mild handling stress. These mice serve as an exciting model in which to examine the neuronal factors that determine vulnerability or resilience to stress.

My laboratory has received continuous funding for our research from the National Institute of Mental Health. Our work has also been supported by the National Alliance for Research on Schizophrenia and Depression, the Pharmaceutical Research and Manufacturers of America Foundation, the San Antonio Area Foundation and the South Texas Health Research Center.

David Morilak, Ph.D.
Department of Pharmacology
(210) 567-4200
(210) 567-4300 fax

Dr. Morilak’s focus of research is on the role of the brain neurotransmitter norepinephrine in the acute behavioral, cognitive and endocrine responses to stress; in adaptive and maladaptive responses to chronic stress; and in the regulatory mechanisms of action of psychotherapeutic drugs.  Central norepinephrine is an important neuromodulatory transmitter which plays a critical role in the response to stress by influencing arousal and sensorimotor response characteristics, and by integrating autonomic responses with behavior.  One of his projects is an investigation of the regulatory changes in gene expression that occur in brain noradrenergic neurons in response to stress, including expression of mRNA for synthetic enzymes, the NE transporter and post-synaptic adrenergic receptors using in situ hybridization.  A related area of interest is the changes produced by chronic stress in the brain noradrenergic system that may contribute to the development of stress-related pathology such as depression, PTSD or anxiety disorders. Experimental approaches include local drug microinjections into stress-related brain regions; in vivo microdialysis to measure neurotransmitter release in behaving rats; in situ hybridization and immunohistochemistry; radioimmunoassay for plasma hormone measures; behavioral measures of cognition, arousal, anxiety and defensive responses application of chronic metabolic and psychogenic stressors.  These studies will help us to better understand the differential roles of monoaminergic neurotransmitters in complex physiological contexts such as the acute stress response, chronic stress-related psychopathology, and the beneficial effects of psychotherapeutic agents such as antidepressants.

Holly Van Remmen, Ph.D.
Cellular and Structural Biology
Barshop Institute for Longevity and Aging Studies
(210) 562-6141
(210) 562-6110 fax

For the past several years, my research focus has been directed at using knockout and transgenic mouse models with altered antioxidant defense systems to test one of the long standing theories of aging, the Oxidative Stress Theory of Aging, that proposes that aging is modulated by life long deleterious effects of oxidative damage.  Our studies have shown that lifespan is not altered in several mouse models with compromised antioxidant defense; data that do not support the long standing Oxidative Stress Theory.  We suggest that oxidative stress is critically important in age related disease, especially cancer, but may not be the major factor underlying aging per se.  One of the antioxidant deficient models we were studying, the CuZnSod null mouse, shows a phenotype of accelerated age related loss of muscle mass and a reduced lifespan.  We are interested in studying the role of mitochondria and oxidative stress on alterations in skeletal muscle that might contribute to the significant problem of age related loss of muscle mass using this mouse model.  In particular, we are interested in studying whether oxidative stress in neurons or in muscle plays a more critical role in the initiation and progression of muscle atrophy. In parallel with these studies, I am also studying the effect of increased mitochondrial oxidative stress on the initiation and progression of the age-associated disease Amyotrophic Lateral Sclerosis.

Texas A&M University

Antonio Cepeda-Benito, Ph.D.
(979) 845-2573
(979) 845-4727 fax

Current theories of drug addiction place learning processes at the core of the development and maintenance of substance abuse. In general, investigators theorize that the distinctive internal (physiological) and external (environmental) stimuli that are reliably present during drug consumption become associated with the effects of drugs. Some theorists affirm that, through Pavlovian and operant conditioning processes, these stimuli can evoke a wide variety of psychological and physiological responses (cravings) that motivate the addict to seek and use drugs.

One of my long-term goals is to contribute to the understanding of the neurobiological basis of associative and pharmacological (nonassociative) tolerance. Another long-term goal is to examine whether associative and nonassociative forms of drug tolerance differentially influence the development of substance dependence, and to what extent these putative effects could be modulated by biological individual differences. However, before the above goals can be investigated, it is imperative to understand how to produce robust associative tolerance phenomena and how to distinguish between associative and nonassociative tolerance. Most of my research has been dedicated to answer the two latter questions.Very recently, we have completed a series of investigations that tested the generalizability of associative tolerance phenomena to nicotine tolerance.

The above research is complemented with psychophysiological investigations where human participants are exposed to drug and food related cues and their cue reactivity is indexed as both physiological (e.g., heart rate) and psychological variables (e. g., craving report). These studies are conducted both in the US and in Spain in collaboration with the Universidad de Granada.

Jim Grau, Ph.D.
Department of Psychology
(979) 845-2584
(979) 845-4727 fax
e-mail: j-grau@tamu.edu

Research in Dr. Grau’s laboratory focuses on two issues: pain modulation and spinal cord function. Recent studies on the topic of pain modulation, conducted in collaboration with Dr. Mary Meagher, have examined the circumstances under which environmental events enhance pain reactivity using a rodent model system. These experiments have shown that exposure to a brief aversive event enhances the affective impact of subsequent aversive stimuli. This effect has been linked to neural systems involved in the regulation of affect (amygdala) and defensive behavior (periaqueductal gray). Another line of research examines plasticity within the spinal cord. Studies in this laboratory have characterized the nature of this plasticity and related the underlying mechanisms to traditional learning phenomena (e.g., Pavlovian conditioning, instrumental learning, and learned helplessness). Recent studies have shown that exposure to a noxious event, independent of the organism’s behavior, can disable behavioral plasticity within the spinal cord. Ongoing studies in the laboratory are focused on the hypothesis that this effect could undermine the recovery of function after a spinal cord injury and experiments are currently exploring this hypothesis using a contusion model. Other studies are using pharmacological manipulations to elucidate the neurochemical systems involved. Results suggest that this type of learning depends on the NMDA receptor and that the behavioral deficit is mediated, in part, by ligands that act on the GABA-A and kappa-opioid receptor systems. In collaboration with Rajesh Miranda (Medical Anatomy) cellular assays are being conducted to uncover the neurochemical mechanisms that underlie spinal cord plasticity.

Mary W. Meagher, Ph.D.
Department of Psychology
(979) 845-2564
(979) 845-4727 fax

Jack R. Nation, Ph.D.
Department of Psychology
(979) 845-2573
(979) 845-4727 fax

My current interests are on the effects of developmental lead exposure on IV cocaine self-administration and on dopamine/glutamate mRNA expression and binding affinity.

Texas A&M Health Science Center

Gerald D. Frye, Ph.D.
Dept. Neurosci. & Experimental Therapeutics (NExT)
(979)845-2888; FAX (979)845-0790

My research focuses on the neuropharmacologic, cellular and molecular mechanisms by which central nervous system (CNS) depressant drugs such as ethanol, anti-anxiety drugs, sedative-hypnotics and general anesthetics cause intoxication. In addition, we are interested in how ethanol intoxication activates adaptive responses in the nervous system to cause acute and chronic functional tolerance, physical dependence and the withdrawal syndrome (ie., DTs). We also study ethanol neurotoxicology in the fetal alcohol syndrome and alcohol related neurodevelopmental disorders where ethanol intoxication has teratogenic actions to disrupt critical periods of neuronal development and cause lasting impairment of cognitive brain function. Studies focus on neurotransmitter receptors (GABA, glutamate, serotonin and acetylcholine) which are targets for ethanol in the adult CNS and which play important roles in neuronal development in the immature developing brain. We are studying the impact of ethanol on the formation and refinement of brain synapses as reflected by altered development of GABAergic miniature potentials. Our primary tools for studying neuronal responses are electrophysiological and include patch clamp whole cell recording in single neurons, in brain slices, acutely isolated from brain slices or in dispersed primary neuronal cell cultures 

William H. Griffith, Ph.D.
Department of Neuroscience and Experimental Therapeutics (NExT)
(979) 845-4991
(979) 845-0790 fax

Over the past several years, our lab has described age-related changes in ligand-gated, voltage-gated calcium channels and calcium homeostasis in basal forebrain neurons. These neurons are involved in attention, arousal, as well as some forms of memory.  The basal forebrain may also have relevance to the clinical symptoms of Alzheimer’s disease in humans. We utilize a rodent model of aging coupled with a variety of techniques including, patch-clamp electrophysiology, microfluorimetric measurements of intracellular calcium concentration ([Ca2+]i), laser scanning confocal fluorescent microscopy, single-cell reverse transcription/polymerase chain reaction (scRT-PCR) and brain slice recordings.  In our aging model, rats are behaviorally characterized based on their performance in the Morris water maze prior to in vitro electrophysiological analysis. The water maze task enables us to separate animals into cognitively impaired and unimpaired groups. Our results support a model in which basal forebrain neurons from aged cognitively impaired subjects modify their physiological properties during aging, and specific mechanisms of Ca2+ homeostasis are altered. We are investigating the cellular and molecular mechanisms of these age-related changes in Ca2+ homeostasis and signaling.

Rajesh C. Miranda, Ph.D.
Department Human Anatomy and Medical Neurobiology
(979) 862-3418
(979) 845-0790

I am interested in the regulation of transitions between cell proliferation, cell suicide and differentiation in the developing central nervous system. Specifically, my research is focused on the mechanisms of estrogen action in the developing cerebral cortex. The estrogen receptor is expressed transiently during the differentiation of the cerebral cortex. We had previously found that there were significant reciprocal regulatory interactions between estrogen and the neurotrophin family of growth factors, in adult neurotrophin targets as well as during periods of neural differentiation. Since the neurotrophins are known to protect against cell suicide in a variety of tissues, we are currently examining whether estrogen and estrogen-neurotrophin interactions can regulate cell suicide in the developing cerebral cortex.  Using a conditionally immortalized cortical cell line that we have developed, we found that both estrogen and the neurotrophins prevent apoptotic cell death. However, estrogen but not the neurotrophins, also promote cell proliferation, suggesting both overlapping and distinct roles for estrogen in the developing cortex.   We are also examining the role of estrogen and the neurotrophins in the regulation of the cell death receptor Fas/Apo-1 in the developing cerebral cortex. Fas/Apo-1 is a member of the tumor necrosis factor receptor/pan-neurotrophin receptor family.  Our research suggests that Fas/Apo-1 mRNA and protein are transiently expressed in neurons, glia and neuroblasts of the cerebral cortex during the peak period of apoptosis.  Fas-L appears to be expressed in by cells in close proximity to Fas expressing cells.  In an explant culture model, we found that estrogen and one neurotrophin (NT-3) specifically regulated the expression of Fas mRNA.   Thus my main research focus deals with how estrogen and estrogen-neurotrophin interactions may regulate cell suicide and cell cycle in the developing cerebral cortex. However, I am developing additional interests that revolve around the phenomenon of cell suicide. One of my collaborations examines the role of neurotropic viruses such as Theiler’s murine enecphalo-myelitis virus in demyelination and cell suicide in the central nervous system. I am also interested in the role of neurotrophic factors in cell death associated with the fetal alcohol syndrome.

Mendell Rimer, Ph.D.
Department of Neuroscience and Experimental Therapeutics (NExT)
(979) 845-4991
(979) 845-0790 fax

My research interests center on the molecular and cellular mechanisms underlying the formation and maintenance of the connections of nerve cells and their targets, the synapses. Because of its simplicity and experimental accessibility we have used the vertebrate neuromuscular synapse as our model system. I am also interested in diseases of the synapse such as schizophrenia and in neuromuscular diseases such as spinal muscular atrophy. We address these problems using state-of-the-art mouse molecular genetic techniques in combination with standard molecular, cellular and immunological approaches.

Farida Sohrabji, Ph.D.
Department of Human Anatomy and Medical Neurobiology
(979) 845-4072
(979) 845-0790 fax

My laboratory is interested in factors that alter the survival and maintenance of neurons in forebrain cognitive circuits. Acetylcholine-synthesizing neurons in the septum-diagonal band project widely within the cerebral cortex, hippocampus and olfactory bulb. Cholinergic neurons and their forebrain targets are at risk in neuropathological disorders such as Alzheimer’s disease. Many of these neurons are targets of the gonadal hormone estrogen and we are interested in the molecular actions of this hormone on forebrain neurons. Previous work has shown that in a rodent model estrogen enhances the expression of the neurotrophin BDNF, which is markedly reduced in the brains of Alzheimer’s disease patients. Estrogen has recently been shown to have a therapeutic effect on Alzheimer’s disease patients, and these data suggest a molecular mechanism by which the hormone may protect vulnerable neurons.   Recent investigations have focused on the identification of novel hormone-regulated genes in the forebrain.  Four novel genes have been identified in the cerebral cortex and olfactory bulb and further studies are designed to clone and characterize these genes and define their role in estrogen-mediated neuronal survival.    Future research will continue to explore the transcriptional events stimulated by estrogen and their cellular consequences in developing and aging forebrain neurons, and expand our investigations to other compounds that affect forebrain cholinergic circuits and affect cognitive behaviors, such as the use of alcohol.

Ursula H. Winzer-Serhan, Ph.D.
Department Neuroscience & Experimental Therapeutics (NExT)
(979) 845-2860
(979) 845-0699 fax

My lab is investigating the effects of nicotine on brain development. Nicotine passes rapidly through the placenta and into the fetus, where the drug interacts with nicotinic acetylcholine receptors (nAChR), ligand-gated pentameric ion channels, which are normally activated by the endogenous ligand acetylcholine. nAChR subunits can form different nicotinic receptor subtypes depending on their subunit compositions. My recent studies have focused on the developmental expression of nAChR subunits in prenatal and postnatal brain, using in situ hybridization and receptor autoradiography. The results show that nAChRs are widely expressed during embryonic and postnatal development and therefore, untimely activation with nicotine could influence developmental processes such as apoptosis, differentiation or synaptogenesis.

Furthermore, stimulation of nAChRs can change the gene expression pattern and induce long-term changes in the developing brain.  On-going projects include: 1. Evaluating the effects of chronic nicotine treatment on brain development. 2. Mapping of the expression of nAChR subunits in the brain using anatomical techniques such as in situ hybridization, receptor autoradiography.   The focus is on characterizing the expression of nAChR subunits in neuronal sub-populations such as cholinergic and GABAergic neurons, to determine the subtype(s) expressed in these neurotransmitter synthesizing cells.