Zinc physiology with a focus on structure, function and regulation of zinc transporters.
Zinc transporters regulate subcellular zinc distributions to ensure proper metalation of numerous zinc enzymes and signaling molecules. Fluctuations of cytosolic zinc concentration constitute the basis for zinc signaling, but also challenge zinc homeostasis with broad disease implications. Our research is focusing on ZnT8, a pancreatic zinc transporter that mediates zinc enrichment in insulin secretory granules. ZnT8 is a major autoantigen in type-1 diabetes. A nonsynonymous variant of ZnT8 is also a validated risk factor contributing to the susceptibility of type-2 diabetes. We are investigating molecular mechanisms underlying the disease risk. Enabling technologies have been developed to study the structure and dynamic of ZnT8 at the molecular level, and its physiological roles in regulating insulin processing and secretion in beta cells. Research findings are being translated to new diagnostic tools and therapeutic interventions for early detection and treatments of diabetes.