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Shelley Hooks, Ph.D.
Assistant Professor
Pharmaceutical and Biomedical Sciences
Office: Room 377, R.C. Wilson Pharmacy
Phone: (706) 542-2189
E-mail: shooks@rx.uga.edu
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Biosketch
| B.S. Biochemistry | Clemson University | Clemson, SC | 1996 | | Ph.D. Biochemistry | University of Virginia | Charlottesville, VA | 2000 | | Postdoctoral Fellow | University of North Carolina-Chapel Hill | Chapel Hill, NC | 2001-2004 | | Assistant Professor | University of Georgia | Athens, GA | 2004-present |
Honors and Awards
Awarded individual postdoctoral F32 NRSA grant (NIGMS), 2002
Founded and organized UNC Women in Science and Research, 2001-2004
Won oral communication award at the Western Pharmacology Society conference, 1999
Awarded individual predoctoral F31 NRSA grant from NIH (NIDA), 1999
Appointed to Cell and Molecular Biology training grant, 1997
Awarded Clemson Scholars scholarship, 1992-1996
Research Interests
Transmembrane receptors and their associated proteins transmit signals across the plasma membrane through conformational changes, enzymatic activity, and formation of multi-protein complexes, allowing cells to respond to external stimuli as diverse as morphine and light with appropriate cellular signaling events, such as neurotransmission. My research focuses on the dynamic regulation of heterotrimeric G-proteins by transmembrane G-protein coupled receptors (GPCRs) and multifunctional Regulator of G-protein Signaling (RGS) proteins. I am broadly interested in defining the molecular mechanisms that govern the physiologic impact of these signaling complexes. Specifically, I am interested in the regulation of dopamine receptor signaling pathways by the striatal RGS protein, RGS9-2. Alterations in dopamine receptor activity in the striatum are implicated in the development of drug addiction and Parkinson’s disease. The ability of RGS9-2 to modulate cellular responses to dopaminergic signaling suggests that RGS9-2 may be a therapeutic target in the treatment of these pathologies.
Recent reports suggest that in cultured cells and in animals RGS9-2 inhibits signaling downstream of D2 dopamine receptors. The mechanism and specificity of RGS9-2 regulation of dopamine signaling and its physiologic relevance is not known. My research program is focused on defining at the molecular level the mechanism, specificity and regulation of RGS9-2 mediated inhibition of signaling downstream of D2 receptor activation. Our approach is two-fold: to define the activity of purified RGS9-2 in biochemical assays, and to compliment this approach with studies in cell culture, representing a more physiologic system. Finally, a mechanistic understanding of RGS9-2 activity in these relatively simple systems will facilitate design of tools to manipulate RGS9-2 mediated regulation of dopamine signaling in animal models and, ultimately, patients. Specific goals are to: 1) define the mechanism and structural requirements for RGS9-2 mediated inhibition of D2 dopamine receptor promoted signaling, 2) determine the G-protein- and receptor-specificity of RGS9-2 activity, and 3) define mechanisms and structural requirements for the regulation of RGS9-2 activity.
Figure 1. Potential RGS9-2 activities and sites of regulation: The striatal-specific RGS9-2 protein contains four well-defined domains and may modulate D2 receptor signaling by multiple mechanisms: (a) the RGS domain may “turn off” GaGTP, (b) the GGL domain, in complex with Gβ5, may couple inactive GaGDP to receptors, allowing them to “turn on”, and (c) the RGS protein may interact directly with the receptor, providing specificity. Further, RGS9-2 activity may be regulated at multiple sites: (d) the unique C-terminal domain may be a regulatory site via phosphorylation or (e) assembly of a signaling complex and (f) RGS9-2 may be tethered to the plasma membrane by DEP domain association with integral membrane proteins such as R9AP.
Techniques used in my laboratory include protein purification, chromatography, cell culture, signal transduction assays, molecular biology, mutagenesis, radiolabeled nucleotide binding assays and GTPase assays. General themes of interest in the laboratory are molecular mechanisms of signal transduction, neuropharmaology, and multi-domain proteins as scaffolding molecules in multi-protein signaling complexes.
Representative Publications
Hooks, S.B. and Harden, T.K. Purification and in vitro functional analysis of R7-subfamily RGS proteins in complex with Gβ5. In Methods in Enzymology, ed. D. Siderovski, 2004, Vol. 390. Elsevier Inc., San Diego.
Jones, M., Siderovski, D., Hooks, S.B. GGL-ing at convention: Novelty and selectivity in the Gâg dimer. Molecular Interventions, 2004, 4: 200-214.
Wu, Y.-L., Hooks, S.B., Harden, T.K., Dohlman, H. Dominant-negative inhibition of pheromone receptor signaling by a single point mutation in the G protein a subunit. Journal of Biological Chemistry, M404896200, 2004.
Hooks, S.B., Waldo, G.L., Corbitt, J., Bodor, E.T., Krumins, A.M., and Harden, T.K.. RGS6, RGS7, RGS9 and RGS11 Stimulate GTPase activity of Gi family G-proteins with differential selectivity and maximal activity. Journal of Biological Chemistry, 2003, 278:10087-10093.
Hooks, S.B., Santos, W.L., Im, D.S., Macdonald, T.L., and Lynch, K.R. Lysophosphatidic Acid induced mitogenesis is regulated by Lipid Phosphate Phosphatases and is Edg-receptor independent. Journal of Biological Chemistry, 2000, 276:4611-4621.
Hooks, S.B., Ragan, S.P., Hopper, D.W., Honneman, C.W., Durieux, M.E., Macdonald, T.L., and Lynch, K.R. Characterization of a receptor subtype-selective lysophosphatidic acid mimetic. Molecular Pharmacology, 1998, 53: 188-194.
Hooks, S.B., Ragan, S.P. and Lynch, K.R. Identification of a novel human phosphatidic acid phosphatase type 2 isoform. FEBS Letters, 1998, 427:188-192.
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