This is a competitive renewal of an Independent Scientist Award (K02 MH01153) for Paul Worley M.D. Dr. Worley is currently an Associate Professor in Departments of Neuroscience and Neurology at The Johns Hopkins School of Medicine and he devotes full time effort to basic research. The focus of research is the molecular basis of protein synthesis-dependent neuronal plasticity. During the tenure of the previous award period, the laboratory has cloned and characterized several novel brain immediate early genes (IEGs) including Cox-2, Homer, Rheb, Narp and Arc. Analysis of the function of these genes has lead to important new insights into how neurons response to activity and this information is broadly relevant to cortex development, drug addiction and memory. The K02 Award has substantially contributed to Dr. Worley's career by assuring stable salary support and allowing him to commit full effort to research and career development. The research plan has been successful based on record of publications and current support by grants (RO-1) from NIHM, NIDA, NINDS and NIA. The Institution is supportive of continued full time research commitment by the P.I. as evidenced by expansion and renovation of laboratory and office space. Plans for future career development will extend the focus of analysis of IEGs to include studies of cellular physiology and system level function. The Research Plan describes our proposed studies of Homer that will examine its role in regulating cellular calcium dynamics and activity-dependent behaviors, including cocaine sensitization. Planned activities make full use of the outstanding opportunities for collaboration and career development at Johns Hopkins School of Medicine.
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