Faculty available for committees

I did my PhD thesis work in the Neuroscience Graduate Program at UNC Chapel Hill from 1979-1985. In Dr. Gerry Oxford’s lab I received training in classical excitable membrane biophysics and used the then emergent technology of “patch clamping” to investigate the mechanism of voltage dependent Calcium channel modulation by biogenic amines in dorsal root ganglion (sensory) neurons. In 1985, I joined Dr. Stephen Smith’s lab in the Section of Molecular Neurobiology and HHMI at YaleUniversity for post doctoral work. I maintained a keen interest in Calcium as a signaling molecule and was hoping to gain some experience in Calcium imaging to compliment my electrophysiological studies; however, by a quirk of scientific fate I began investigating neuronal growth cone motility using high resolution video enhanced DIC microscopy. This unexpected turn of events led me directly into the study of cell motility –a descriptive field of research at the time, especially when compared to the quantitative realm of ion channel biophysics which I was accustomed to. Working in cell motility necessitated learning about cytoskeletal protein dynamics and function, and I embarked on the road to becoming a cell biologist.In 1989 I started my lab in the Department of Biology (now the Department of Molecular, Cellular, and Developmental Biology) at Yale University. Our research initially focused on characterizing the cytoskeletal protein dynamics and molecular motor activity underlying growth cone motility. Over the years I have maintained an interest in understanding how classical signal transduction pathways (Ca, PKC, PKA, etc.) modulate cytoskeletal machinery to affect axon growth and guidance.To investigate mechanisms of growth cone guidance, we developed an in vitro turning assay using silica bead substrates coated with attractive cell adhesion molecules. These bioassays were first used to identify signal transduction pathways involved in substrate dependent growth cone turning and to characterize the role traction forces play in axon advance. A role for src family tyrosine kinases as mechano-transduction sensors emerged from this work.Recently we have been developing biophysical methods for measuring traction forces that growth cones exert on the underlying substrate while co-assessing cytoskeletal dynamics with fluorescently tagged proteins. These studies yield quantitative data amenable to mathematical modeling of the fundamental processes underlying neuronal growth and regenerative processes.

Dr. Charles A. Greer is the Vice Chair for Research and holds the rank of Professor of Neuroscience. Dr. Greer also serves as Director of the Yale Interdepartmental Neuroscience Graduate Program. He has served as the President of the Association for Chemoreception Sciences, Chair of National Institutes of Health Study Sections and recently completed a term on the Advisory Council for the National Institute of Deafness and Other Communicative Disorders. He has organized several national and international conferences and is frequently an invited speaker. Dr. Greer is an Associate Editor of The Journal of Comparative Neurology and Journal of Neuroscience and a member of the editorial boards of Frontiers in Neurogenomics, Frontiers in Neuroanatomy and Frontiers in Neuorgenesis and the Faculty of 1000. Dr. Greer has been the recipient of numerous awards recognizing his research accomplishments.

Horwich received undergraduate and M.D. degrees from Brown University, trained in Pediatrics at Yale, was then a postdoctoral fellow first at Salk Institute in the Tumor Virology Laboratory, and then in Genetics at Yale, then joined the Yale faculty. His work was initially involved with protein import into mitochondria and resulted in discovery of a "folding machine" inside mitochondria, Hsp60. He has used genetic, biochemical, and biophysical tools to study the mechanism of action of these ring shaped so-called chaperonin machines that provide essential assistance to protein folding in many cellular compartments. More recently he has focused on neurodegenerative disease, modeling mutant SOD1-linked ALS in mice transgenic for a mutant SOD1 fused with a YFP reporter. In the transgenic mutant strain, the mutant SOD1 misfolds and lodges the fusion protein in YFP fluorescent aggregates, visible in motor neurons by 2-3 months of age. These neurons are removed by microglial cells, associated with loss of ~50% of motor neurons. By 6-7 months of age the mice exhibit lower extremity paralysis, associated with loss of ~50% of the remaining motor neurons. By contrast, a wtSOD1-YFP transgenic strain with the same amount of total SOD1-YFP protein in spinal cord remains asymptomatic even after two years, and the spinal cord remains free of aggregates. An early study showed that overexpression of the molecular chaperone Hsp110, known to be part of a chaperone disaggregase, improved survival of the SOD1-YFP mice. Additional genetic modifiers are being tested.

Angus Nairn did his undergraduate training in biochemistry at the University of Edinburgh, Scotland and his PhD in muscle biochemistry in the laboratory of Professor Sam Perry at Birmingham University, England. He then carried out postdoctoral research in molecular neuroscience with Professor Paul Greengard at Yale, and moved with Professor Greengard to Rockefeller University in 1983 as a faculty member. He moved back to Yale University in 2001, where he is currently the Charles B.G. Murphy Professor of Psychiatry. He also holds a joint appointment in the Department of Pharmacology and is co-director of the Yale/National Institute of Drug Abuse Neuroproteomics Center at the Yale School of Medicine.

Michael Nitabach JD, PhD is faculty member of Molecular Cell Biology, Genetics and Development, Molecular Medicine, Pharmacology and Physiology, and Interdepartmental Neuroscience Program. He is affiliated with the Program in Cellular Neuroscience, Neurodegeneration and Repair. He received a PhD from Columbia University and a JD from New York University.

Professor Rudnick is a graduate of Antioch College, where he received a B.S. in Chemistry in 1968. He performed graduate studies in the enzymology of amino acid racemases in the laboratory of Robert H. Abeles in the Graduate Department of Biochemistry at Brandeis University, receiving a Ph.D. in Biochemistry in 1974. His graduate studies led to an understanding of the structure and mechanism of proline racemase that was confirmed by the crystal structure of a homologous protein in 2006. From 1973-1975, Professor Rudnick performed postdoctoral research on lactose permease with H. Ronald Kaback at the Roche Institute of Molecular Biology. This work provided a greater understanding of binding and transport reactions using photoaffinity reagents and substrate analogs. In 1975, he left Roche to become an Assistant Professor in the Department of Pharmacology at Yale, and was promoted to Associate Professor in 1980 and Professor in 1991. Professor Rudnick’s research at Yale has focused on the mechanism and structure of mammalian serotonin transporter (SERT). He developed a system of platelet plasma membrane vesicles with which to study the bioenergetics and mechanism of transport. These studies provided an understanding of the coupling of ion gradients to serotonin accumulation and also identified SERT as the molecular target for the antidepressant imipramine and the psychostimulant MDMA (ecstasy). Beginning in the 1990s, Professor Rudnick’s laboratory has been studying the molecular characteristics of SERT and other neurotransmitter transporters expressed in cultured cells. These studies led to the identification of the serotonin binding site in SERT and of regions in the protein undergoing conformational changes during transport. The availability of a crystal structure for a homologous bacterial transporter in 2005 allowed Professor Rudnick and his colleagues to use the conformational changes to propose a conformational mechanism of transport that is gaining wide acceptance. Because SERT is structurally related to many other transporters, the proposed mechanism is likely to apply to transporters functioning in many diverse biological systems. In addition to these mechanistic studies, Professor Rudnick’s laboratory has been investigating a spontaneously occurring SERT mutant associated with several psychiatric disorders. The mutation apparently inhibits removal of a phosphate group added to SERT by cGMP-dependent protein kinase. The mechanism by which this phosphate increases SERT activity is an active area of investigation.