Shelley B. Hooks

Research in my laboratory 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. We are broadly interested in defining the molecular mechanisms that govern the physiologic impact of these signaling complexes. A primary interest in the lab is the multi-domain striatal RGS protein, RGS9-2, which regulates dopamine receptor signaling. Alterations in dopamine receptor activity in the striatum are implicated in the development of drug addition 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. Specific projects are being pursued to define novel RGS domain-independent functions of RGS9-2 and to define the receptor- and pathway-specificity of RGS9-2 function.

A second major area of interest in the laboratory is to define the role of RGS proteins in the development and progression of Ovarian Cancer. G-protein activation by receptors is a well-studied factor in ovarian cancer pathology, but the role of counter-regulation of G-proteins by RGS proteins is largely unknown. Open projects in the lab seek to characterize RGS expression in normal and cancerous ovarian tissue, and delineate the role of these RGS proteins in the regulation of cancer-related phenotypes such as growth, migration, and apoptosis.

Diverse biochemical and cellular techniques are used in the lab to address these biological questions:
-- General molecular approaches: PCR, molecular biology, SDS-PAGE protein gels, immunoblotting, cell culture, transfection.
-- Cell signaling studies: second messenger assays (IP3 and cAMP), immunoprecipitation and siRNA.
-- Protein biochemistry: Protein purification, proteoliposome reconstitution, radioligand binding, enzyme kinetics.