Laboratories
(Partial Listing)

Timothy C. Cope, Ph.D.
Director, Comprehensive Neuroscience Center
Chair and Professor, Department of Neuroscience, Cell Biology and Physiology

My research interests center on motor control and sensorimotor integration in the mammalian spinal cord. Using predominantly electrophysiological methods we study spinal motoneurons, muscle stretch afferents, and their center synapses. We are actively examining how these neurons and synapses respond soon and long after peripheral nerve injury and after manipulations in the functional relations between nerve and muscle. These studies are yielding insight into factors that influence the function and dysfunction of sensorimotor circuits in adult animals. In addition we are studying activity patterns among populations of motoneurons recruited during movement in order to infer strategies and mechanisms used by the central nervous system to control movement. Ongoing collaborative efforts involve studies in motoneuron disease, activity dependence of synaptic function, and neurotransmitter receptor expression.

Francisco J. Alvarez, Ph.D.
Associate Professor of Neuroscience, Cell Biology, and Physiology
Director of Microscopy Core Facilities

Our lab is interested in the development of synaptic circuits in the spinal cord. Newborns express immature spinal circuits reflected in abnormal reflexes and limited capacity to make effective postural adjustments or fine movements. The neurobiological principles that drive the postnatal maturation of spinal cord motor circuits, in particular the development of inhibitory synapses and interneurons that modulate motoneuron activity, are largely unknown. Our laboratory uses electron microscopy, confocal microscopy and electrophysiological methods to study the postnatal maturation of structure, molecular composition and synaptic function of key inhibitory circuits in the spinal cord. Our latest work analyzes the postnatal specification of adult inhibitory interneurons from embryonic spinal neuronal groups. Using transgenic mice that carry linage markers for the subpopulation of embryonic neurons derived from the V1 group, we have shown that several different types of segmental ventral inhibitory adult interneurons derive from this group and therefore share a similar genetic background.

Francisco Javier Alvarez-Leefmans, M.D., Ph.D.
Professor of Pharmacology and Toxicology

Research in my laboratory is funded by NIH and involves two tightly linked areas: 1.) Mechanisms regulating intracellular chloride in neurons and their impact on GABA-mediated synaptic inhibition — Our long-term objective in the first area is to understand the molecular mechanisms that determine the concentration of intracellular chloride (Cl-) in primary afferent neurons (PANs), their regulation and the role they play in acute somatic pain and neurogenic inflammation. PANs convey sensory information from the body to the central nervous system. Electric signals arising from peripheral sensory receptors enter the spinal cord and the brain stem through the central processes of PANs and ultimately evoke sensations such as touch, warmth, cold and pain. Work originating in my lab established that the depolarizing action of GABA is possible because [Cl-]i in PANs is higher than predicted for electrochemical equilibrium due to Na+,K+,2 Cl- cotransporters, membrane proteins that actively accumulate Cl-. 2.) Cellular and molecular mechanisms underlying cell volume control under normal and pathophysiological conditions in neurons and glial cells — We are currently focusing on the mechanisms underlying short-term changes in cell water volume and intracellular H+, Ca2+ and Cl- produced by exposure to ammonia (NH3) and ammonium (NH4+). These studies are important for understanding the pathophysiology of cellular brain edema that follows increased blood levels of NH3 and NH4+ (hyperammonemia) in humans with acute liver failure. Hyperammonemic brain edemas are a leading cause of mortality in patients with acute liver failure. We have developed in vitro models and optical methods for studying the pathophysiology of these edemas at the cellular and molecular levels.

Steven J. Berberich, Ph.D.
Interim Chair and Professor, Department of Biochemistry and Molecular Biology

Our laboratory has been studying cellular regulators of the p53 tumor suppressor protein since 1993. Our first NIH grant focused on examining the role of the Mdm2 protein on regulating p53 function. Those studies led several novel discoveries, including an Mdm-2 chromosomal translocation, Mdm-2 gene amplification and Mdm-2 phosphorylation. We then began to study MdmX, a Mdm2-related gene that, unlike Mdm2, was not p53-regulated. Our subsequent NIH grant focused on the role of MdmX protein on p53 function. Our current five-year NIH grant continues our studies on MdmX but combines RNAi approaches with our gene expression profiling capabilities of the Center for Genomics Research (CGR) in an effort to further understand the effects of MdmX deregulation on the p53 pathway. Our primary goal is to test whether loss of MdmX can improve cancer therapies in human tumors harboring wild-type p53 that is inactivated by the deregulation of either Mdm2 or MdmX. While the majority of our research has focused on p53 regulators, the CGR has enabled us to initiate several new research collaborations. One project examining the role of 2-deoxy-glucose treatment of glioblastomas prior to irradiation has led to a recent publication with a group in India and a pending clinical trial where CGR will provide gene expression profiling of glioblastoma biopsies. Collaborations involving rat skin toxicogenomics, schizophrenic patient genotyping and lung cancer gene expression profiling are currently ongoing.

David R. Cool, Ph.D.
Associate Professor of Pharmacology and Toxicology
Director, Proteome Analysis Laboratory

The focus of my laboratory is to investigate the proteome and genome of the hypothalamic, pituitary, adrenal, pancreatic-axis (HPAP-Axis) under normal, disease or chemically challenged conditions. My research involves studying the expression, sorting, processing and secretion of HPAP peptide hormones such as vasopressin, oxytocin, insulin and ACTH. I am currently funded to study these processes in diseases such as familial neurohypophyseal diabetes insipidus, type 1 diabetes, autism and in response to nerve agents such as sarin. My long term goals are to identify and investigate the effects that these disease have on the regulation and dysfunction of the neuroendocrine system.

Kathrin Engisch, Ph.D.
Associate Professor Neuroscience, Cell Biology, and Physiology

Our laboratory uses highly specialized electrophysiological measurements in combination with genetic manipulations of individual synaptic proteins, to study the basic mechanisms of neurotransmitter release and its modulation. Neurotransmitter release shows dramatic activity-dependent behaviors. Rapid repetitive stimulation can cause an increase in release, called facilitation, in some nerve terminals. In others, the same protocol can cause depression, or a decrease in release. These types of short-term plasticity are essential for information processing in the brain, but the underlying mechanisms are unknown. We are currently studying the characteristics of neurotransmitter release in a Rab3A mutant mouse. We are also interested in longer term regulation of neurotransmitter release by activity. In collaboration with Mark Rich's laboratory, we have found that block of activity causes increases in synaptic strength by increasing the number of vesicles that fuse, and the size of the individual release events. We are currently examining the role of particular synaptic proteins in this long term plasticity.

Robert E.W. Fyffe, Ph.D.
Associate Dean for Research Affairs
Professor of Neuroscience, Cell Biology, and Physiology

Our laboratory is interested in synaptic mechanisms and integrative properties of neurons in spinal cord and brainstem circuits, involved in motor control and auditory processing respectively. Current studies are focused on the patterns of expression, and the subcellular localization, of pre- and post-synaptic membrane ion channels and neurotransmitter receptors. We use a range of quantitative light and electron microscopic experimental and analytical methods, in conjunction with electrophysiological and computation approaches. Our primary collaborators, in addition to colleagues within the department, include Bruce Walmsley (Australian National University), Ken Rose (Queen's University, Kingston, Ontario) and Brian Robertson (University of Leeds, UK)

Michael Hennessey, Ph.D.
Professor of Psychology

Our laboratory studies the relation between neuroendocrine activity and behavior, particularly during development. Hormones (endocrines) have important influences on adaptive behavior. But not all effects of hormones are adaptive. For instance, prolonged activation of the body’s primary stress-related neuroendocrine system, the hypothalamic-pituitary-adrenal (HPA) axis, may impair both our physical and mental health. Because psychological “stressors”, such as exposure to novel or uncertain situations, can activate the HPA axis, and because other psychological factors, such as the presence of an important social companion (an attachment figure) can inhibit HPA activation, psychological factors may have important influences on our well being. Young organisms appear to be particularly susceptible to such effects. Therefore, it is important to better understand how behavior, psychological factors, and endocrine activity are related in young organisms.

Douglas S. Lehrer, M.D.
Associate Professor of Psychiatry
Medical Director, Boonshoft Schizophrenia Center

The Department of Psychiatry undertakes neurobiological research in partnership with the Wallace-Kettering Neuroscience Institute (WKNI) located at the nearby Kettering Memorial Hospital, home of fully equipped positron emission tomography (PET) and magnetic resonance imaging (MRI) labs, including research-dedicated facilities supported by a full staff of Ph.D.-level radiochemists, physicists, and computer scientists. My group is conducting a number of investigations into the neurobiology of psychoses, including a study of pathophysiology of never- and unmedicated schizophrenics using PET (FDG and fallypride), MRI (structural, functional, diffusion tensor), neurological and neuropsychological examinations; a study to identify biomarkers of differential antipsychotic treatment response (again, using PET, MRI, neuropsychological and neurological variables, as well as pharmacogenomic markers); a study of non-verbal language characteristics of schizophrenic subjects using advanced computer-assisted analysis of audio/video recordings; and a study of self-injury in women with borderline personality disorder using functional MRI.

Mark Rich, M.D., Ph.D.
Associate Professor of Neuroscience, Cell Biology, and Physiology
Director, Neurological Medicine

My research focuses on two areas. We study the cause of paralysis in patients with Critical Illness Myopathy. We have found that paralysis in this syndrome is due to abnormal behavior of skeletal muscle sodium channels. Our goal is to determine the cause of altered sodium channel behavior. We study the mechanisms underlying activity-induced changes in synaptic strength. We use the neuromuscular junction as a model synapse in which it is possible to determine both the signals triggering changes in synaptic strength as well as the types of changes underlying alterations in synaptic strength.