Modulating proteins within G protein coupled receptor signaling pathways that are implicated in cancer and pain: RGS17 and adenylyl cyclase type 1

Research laboratories and clinics have identified novel drug targets and provided insights into the relative cause and effect for disease states like cancer and chronic pain. Certain proteins have been identified as having elevated levels or being overactive in their respective disease state(s). Efforts to develop novel treatment options have used small molecules to tune activity in certain disease states to further our understanding of how the altered abundance or activity of these proteins contributes to the disease state in question. Further, small molecules capable of restoring the natural function of these identified proteins represent potential therapeutics worth pursuing. Given the tremendous social and economic burden associated with cancer and chronic pain conditions there is a need for new approaches to the treatment of cancer and chronic pain.

My doctoral work has focused on probing two classes of proteins to better understanding their role in G protein coupled receptor (GPCR) signaling. First, the regulator of G protein signaling (RGS) proteins that modulate GPCR signaling through their interaction with Gα proteins. One member of the RGS family that has received attention as potential drug target is RGS17, which is found to be overactive or overexpressed in breast, lung, prostate, and hepatocellular carcinomas. My work has focused on furthering our understanding of RGS17 activity and the role of novel regulatory partners. The second class of proteins is the adenylyl cyclases (AC), which are downstream GPCR signaling molecules that produce the second messenger cAMP. One family member, AC type 1 (AC1) has been found to be overactive in chronic inflammatory pain. My work has focused on the identification of small molecules capable of reducing AC1 activity to provide novel treatment options for chronic inflammatory pain conditions.