John Sondek, Ph.D.

Research

Our laboratory studies signal transduction systems controlled by heterotrimeric G proteins as well as Ras-related GTPases. The superfamily of GTPases control numerous signaling cascades based upon the regulated binding, hydrolysis, and exchange of guanine nucleotides; GTP-bound GTPases are active in downstream signaling while those bound to GDP are inactive. Mutant GTPases with abnormal GDP/GTP cycling are implicated in numerous human diseases, including cancer. It is our desire to better understand the regulation of heterotrimeric G proteins and Ras-related GTPases at the molecular level with the ultimate goal of using this information to design therapies to correct abnormal signaling mediated by these proteins and thereby treat associated pathologies. Current major initiatives in the laboratory include: 1) Defining the regulation of phospholipase C isozymes by heterotrimeric G proteins and small GTPase 2) Understanding the activation of Rho GTPases by guanine nucleotide exchange factors 3) Studies to elucidate the functions of RGS proteins 4) High throughput structural proteomics