Assistant Professor of Medicine, Pathology and Immunology
Dr. Levisetti received his medical degree from the University of Chicago Pritzker School of Medicine in 1996. He did his clinical training in internal medicine at the University of Chicago Hospitals (1998-2000). He did his subspecialty training in endocrinology at Washington University School of Medicine and the Barnes-Jewish Hospital, where he also obtained postdoctoral research training in immunology with Emil R. Unanue (2000-2004). Dr. Levisetti has been the recipient of grants from the Howard Hughes Medical Institute, the American Diabetes Association, and the National Institutes of Health. Dr. Levisetti joined the faculty in the Department of Medicine in 2004, and has a joint appointment in the Department of Pathology and Immunology.
The mechanism by which loss of tolerance to self tissues occurs is a fundamental question in immunology. This loss serves as the pathophysiologic substrate for many human diseases, including Type 1 diabetes mellitus. The work in my laboratory focuses on the molecular mechanisms that lead to the autoimmune destruction of the insulin producing beta-cells of the pancreas. To this aim, we have pursued cellular and biochemical approaches to: (1) the identification of novel beta-cell autoantigens using an approach based on the generation of monoclonal antibodies from prediabetic mice in the NOD (Non-Obese Diabetic) mouse model, (2) the detailed characterization of T cell reactivity against newly identified beta-cell autoantigens, and known antigens such as proinsulin and its processing products, C-peptide and insulin, (3) investigations into the mechanisms of beta-cell antigen processing and presentation by antigen presenting cells (APC). Together these aims will further our understanding of the processes that lead to autoimmune diabetes and suggest interventions to reverse or prevent this disease.
It is likely that the applications of this work will extend beyond our current areas of research, given that many human diseases are caused by the autoimmune destruction of endocrine glands, resulting in deficiencies of hormones required for normal metabolism and health. In the case of type 1 diabetes, pancreatic beta-cell destruction leads to a deficiency of insulin. Autoimmunity is responsible for most cases of primary hypothyroidism and adrenal insufficiency as well. Given the propensity for endocrine glands and cells to be targets of autoimmune disease, my laboratory focuses on defining the molecular pathways involved in secretory cell targeted autoimmunity.