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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH001152-09
Application #
6638873
Study Section
Special Emphasis Panel (ZRG1-MDCN-7 (02))
Program Officer
Sieber, Beth-Anne
Project Start
1995-09-30
Project End
2005-04-30
Budget Start
2003-07-01
Budget End
2004-04-30
Support Year
9
Fiscal Year
2003
Total Cost
$124,821
Indirect Cost
Name
Johns Hopkins University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Szumlinski, Karen K; Dehoff, Marlin H; Kang, Shin H et al. (2004) Homer proteins regulate sensitivity to cocaine. Neuron 43:401-13
Diagana, Thierry T; Thomas, Ulrich; Prokopenko, Sergei N et al. (2002) Mutation of Drosophila homer disrupts control of locomotor activity and behavioral plasticity. J Neurosci 22:428-36
Lu, W; Marinelli, M; Xu, D et al. (2002) Amphetamine and cocaine do not increase Narp expression in rat ventral tegmental area, nucleus accumbens or prefrontal cortex, but Narp may contribute to individual differences in responding to a novel environment. Eur J Neurosci 15:2027-36
Potschka, H; Krupp, E; Ebert, U et al. (2002) Kindling-induced overexpression of Homer 1A and its functional implications for epileptogenesis. Eur J Neurosci 16:2157-65
Boudin, H; Doan, A; Xia, J et al. (2000) Presynaptic clustering of mGluR7a requires the PICK1 PDZ domain binding site. Neuron 28:485-97
Tu, J C; Xiao, B; Naisbitt, S et al. (1999) Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron 23:583-92
Beilharz, E J; Zhukovsky, E; Lanahan, A A et al. (1998) Neuronal activity induction of the stathmin-like gene RB3 in the rat hippocampus: possible role in neuronal plasticity. J Neurosci 18:9780-9
Tu, J C; Xiao, B; Yuan, J P et al. (1998) Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron 21:717-26
Xiao, B; Tu, J C; Petralia, R S et al. (1998) Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins. Neuron 21:707-16
Ingi, T; Krumins, A M; Chidiac, P et al. (1998) Dynamic regulation of RGS2 suggests a novel mechanism in G-protein signaling and neuronal plasticity. J Neurosci 18:7178-88

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