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The Department of Biomedicine

BBB seminar: Thomas Wilkie

Gq-RGS signaling in caloric restriction and pancreatic cancer

Thomas Wilkie
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA

Research in my group is devoted to understanding mechanisms of G protein signaling in mammalian development, energy homeostasis, and pancreatic disease. In an early collaboration with Mel Simon at the California Institute of Technology, the four classes of metazoan G proteins (Gs, Gi, Gq, G12) were identified. While starting up my laboratory at UT Southwestern Medical Center, collaborative work with Alfred Gilman´s group then showed that regulator of G-protein signaling (RGS) proteins are GTPase activating proteins (GAPs) for G protein alpha subunits. From collaboration with the Shmuel Muallem group it was demonstrated that RGS proteins initiate calcium oscillations evoked by Gq protein-coupled receptor (GPCR) agonists in pancreatic acinar cells, and are feedback regulated by calcium-calmodulin and PIP3. Further experiments revealed that a Rgs16::GFP reporter gene is expressed in pancreatic ductal adenocarcinoma (PDA), from the earliest lesions and throughout tumor progression. Recent studies in knockout mice show that Rgs genes are tumor suppressors at each stage of PDA initiation and progression, from precancerous pancreatitis to metastasis.

Chairperson: Nils Halberg, Department of Biomedicine