Amy Clark, DO

Instructor in Pediatrics, Endocrinology and Diabetes

Research Interest

Islet Biology and Immunology

Prevention and Control


Category(ies) of Research

Basic

Translational


Description of Research

The goal of my research is to delineate the molecular mechanisms of beta cell death resulting in type 1 diabetes (T1DM) as a means to identify novel beta cell preserving therapies for diabetic patients. My current research focuses on the identification of novel beta cell intrinsic molecular pathways involved in islet inflammation and beta cell death in T1DM. My current efforts are directed toward targeting these inflammatory and cell death pathways in beta cells to protect them from autoimmune destruction. My approach is based upon recognition of the critical role of an elaborate ER network for insulin production and the increased sensitivity of beta cells to ER stress. One area of my research is directed toward elucidation of relationships between ER stress-mediated disruptions of calcium homeostasis and autoimmune mediated beta cell death. My research has shown that pharmacologic preservation of cellular calcium homeostasis can prevent cytokine mediated beta cell death in vitro. Further studies are underway to determine if these compounds are protective against diabetes in the low dose STZ and NOD mouse models of autoimmune diabetes. I am also actively studying the role of beta cell driven sterile inflammation in islet inflammation. Recent studies indicate that the ER stress related protein thioredoxin interacting protein (TXNIP) might be a key molecular mediator of islet inflammation and beta cell death in diabetes. Studies are underway utilizing in vivo and in vitro TXNIP knock out models to delineate the role and mechanism of TXNIP in beta cell death.