Autoimmune Pathogenesis of Type 1 Diabetes

My research focuses on mechanisms of autoimmunity that result in destruction of pancreatic beta-cells and development of insulin-dependent diabetes mellitus (IDDM). There are three main target antigens in this process: the smaller isoform of the GABA-synthesizing enzyme glutamic acid decarboxylase, GAD65; a tyrosine phosphatase, IA-2; and a heavily glycosylated membrane protein named glima 38. Current research projects focus on four main areas: (i) structure, function, and cell biology of GAD65, IA-2 and glima 38; (ii) characterization of disease-specific B-cell epitopes in GAD65, and IA2 and the temporal pattern of their recognition during early and late phases of beta-cell destruction; (iii) characterization of autoimmune T-cell epitopes in GAD65 and IA2 and how they can be used to induce apoptosis in autoimmune T-cells during the preclinical phase to prevent disease; (iv) mechanisms of transplantation tolerance and development of methods to prevent allo- as well as autoimmune destruction of islet cell transplants.