Assistant Adjunct Professor

Our research program is centered on defining molecular and cellular mechanisms of immune tolerance versus autoimmunity. Currently, our main focus is to examine pathways underlying the function of autoreactive and regulatory T cells in the development of autoimmune diseases. The Non-Obese Diabetic (NOD) mouse is an invaluable model for the study of autoimmune diabetes. Furthermore, although less appreciated, NOD mice are susceptible to other autoimmune diseases which can be differentially manifested by varying T cell co-stimulatory pathways. For instance, we showed that altering the interaction of co-stimulatory molecules CD28 and B7-2 prevented diabetes in NOD mice by restoring an adequate balance of regulatory versus autoreactive T cells. Interestingly, although NOD-B7-2KO mice were protected from diabetes, they developed a spontaneous autoimmune disease of the peripheral nervous system, called Spontaneous Autoimmune Peripheral Polyneuropathy (SAPP) and reminiscent of multiple autoimmune diseases occurring in individuals or families prone to autoimmunity. We have generated NOD mouse models that develop either diabetes alone, SAPP alone, or both autoimmune diseases concomitantly. Surprisingly, autoimmune diabetes and neuropathy depended on distinct genetic and pathogenic pathways even though they occur in the same autoimmunity prone background. We are now pursuing our efforts to delineate common versus disease-specific pathways of autoimmunity in the NOD mouse. The results of these studies will impact on our understanding of the immunopathology of different autoimmune diseases and may lead to innovative therapeutic strategies for these debilitating diseases in susceptible individuals.