The ASPIRE Path in Molecular Medicine

For my PhD, I will be studying diabetes, a complex metabolic disorder characterized by chronic hyperglycemia and affecting approximately 38.4 million people in the U.S. Diabetes arises in part from dysregulation of pancreatic islet hormone secretion and action. In particular, glucagon secretion from pancreatic α-cells is abnormally elevated in diabetes, contributing significantly to hyperglycemia. However, the mechanisms underlying this dysregulation remain poorly understood. Intriguingly, diabetes is also associated with elevated levels of circulating vasopressin (AVP), suggesting it may play a role in disease pathogenesis. AVP activates V1bR, a Gq-coupled receptor encoded by Avpr1b that is selectively expressed in pancreatic α-cells. My research aims to investigate how V1bR signaling influences α-cell function and glucagon secretion using an α-cell-specific knockdown mouse model. The objective of this project is to define the role of α-cell V1bR in regulating glucagon secretion and maintaining glucose homeostasis in healthy and diseased states. Ultimately, the long-term goal is to explore whether targeting Gq-coupled receptors or their downstream pathways could be a viable therapeutic strategy to reduce hyperglucagonemia and improve glycemic control in diabetes.