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HOCK 329
Phone: 765-494-1807

G protein-coupled receptors (GPCRs) are responsible for the sensation of sight and smell, regulation of blood pressure and heart rate, and control of cell growth and migration. Signals impinging upon the exterior of the cell induce a conformational change in these GPCRs, instigating intracellular cascades that lead to profound physiological change. Dysfunctional signaling can lead to heart failure, hypertension, and tumor growth and metastasis. We study the molecular basis of GPCR-mediated signal transduction, principally via the technique of X-ray crystallography. By determining atomic structures of signaling proteins alone and in complex with their various targets, we can provide novel insights into the molecular basis of signal transduction and disease. The lab is also interested in rational drug design and the development of biotherapeutic enzymes. We currently have a robust drug development program aimed at a family of GPCR kinases (GRKs) wherein we are seeking to identify potent and selective inhibitors of GRKs involved in cardiovascular disease. We also are investigating GPCR regulated RhoGEFs that play significant roles in uveal melanoma and breast cancer. Another area of interest is a small family of human phospholipases that includes LPLA2, a lysosomal enzyme important for the function of alveolar macrophages, and LCAT, a key enzyme in reverse cholesterol transport. These enzymes are important biotherapeutic and small molecule targets for the treatment of high cholesterol and lipid storage diseases, respectively.

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