Robert S. Sherwin, M.D. C.N.H. Long Professor of Medicine Section of Endocrinology Interim Section Chief Department of Internal Medicine 333 Cedar Street P.O. Box 208020 New Haven, CT 06520-8020 USA Email: robert.sherwin@yale.edu Telephone: (203) 785-4183 Fax: (203)737-5558

Robert S. Sherwin. MD is the C.N.H. Professor of Medicine in the Section of Endocrinology at Yale University School of Medicine in New Haven, CT. He graduated from the Albert Einstein College of Medicine in 1967. After completing his residency in internal medicine at Mount Sinai Hospital, New York, he moved to the National Institutes of Health Gerontology Research Center to undertake a fellowship in metabolism and diabetes. In 1972 Dr Sherwin moved to Yale University School of Medicine as a postdoctoral fellow and was subsequently appointed to the faculty in 1974. He serves as the Director of the Yale General Clinical Research Center, of the Diabetes Endocrinology Research Center and the JDRF Center for the Study of Hypoglycemia at Yale. His special clinical interests include patients with type 1 diabetes, intensified insulin therapy, complicated type 2 diabetes patients, and hypoglycemia associated with diabetes. Dr Sherwin’s research activities are focused on areas: glucose counter regulation and the immune mechanisms leading to type 1 diabetes mellitus. The studies dealing with counter regulation examine the brain glucose sensing mechanisms mediating the activation of counter regulatory responses and the impact of hypoglycemia on brain function. Animal models have been developed and brain microdialysis technologies incorporated to determine the site of the CNS glucose sensor and the molecular mechanisms of hypoglycemia-associated autonomic failure. Research in immunology has led to the isolation of islet-specific T cell clones from diabetic mice that adoptively transfer diabetes. The program focuses on the development of vaccines for diabetes prevention and genetically modified diabetic mice that express human diabetes associated genes. He has served as President of the American Diabetes Association and as a member of the FDA Advisory Committee for Endocrinologic and Metabolic Drugs. He is editor of one of the major medical textbooks on diabetes mellitus and wrote the chapter on diabetes for the Cecil Textbook of Medicine. Dr. Sherwin has served as the Chairman of the Medical Science Advisory Board of the JDRF and on the editorial boards of leading diabetes and endocrine journals. He has published over 300 articles in peer reviewed journals. Dr. Sherwin is the recipient of the Novartis Award for long-standing achievement in diabetes and 2 MERIT Awards from NIDDK.

Research

Research activities are focused in two areas: 1) glucose counterregulation and 2) the immune mechanisms leading to IDDM.

The studies dealing with counterregulation examine the glucose thresholds activating counterregulatory responses and the sensitivity of the brain to hypoglycemia. We have found that diabetes leads to a upward setting of plasma glucose thresholds for counterregulation and that intensive treatment lowers these thresholds to values below normal. The changes in diabetes appeared to be mirrored by similarly directed alterations in the capacity of hypoglycemia to alter cortical and brain stem evoked potentials. Animal models have been developed and brain microdialysis technologies incorporated to determine the site of the CNS glucose sensor and the neurotransmitters involved in triggering counterregulatory responses and the local changes in glucose transport and utilization within brain extracellular fluid in response to hypoglycemia.

Research in immunology has led to the isolation of islet-specific T cell clones from diabetic mice that adoptively transfer diabetes. The program focuses on molecular and cell biology, genetically modified (transgenic) rodents, and basic immunobiology. Recent work focuses on diabetogenic and disease suppressive T cells that recognize peptides derived from beta cell autoantigens (GAD, and insulin). In addition, we have generated transgenic mice that express HLA genes linked to type 1 diabetes. The goal is to use the data obtained in genetically altered mice to isolate and clone diabetes producing T lymphocytes from humans. Such cells may provide a tool for developing new strategies for immunotherapy. Finally, we are developing gene therapy approaches for prevention of type 1 diabetes as well as insulin delivery.

1. Borg MA, Sherwin RS, Borg WP, Tamborlane WV, Shulman GI. Local ventromedial hypothalamus glucose perfusion blocks counterregulation during systemic hypoglycemia in awake rats. J Clin Invest 99:361-365, 1997.
2. Wen L, Wong FS, Burkly L, Altieri M, Mamalaki C, Kloussis D, Flavell RA, and Sherwin RS. Induction of insulitis by glutamic acid decarboxylase peptide-specific and HLA-DQ8-restricted CD4+ T cells from human DQ transgenic mice. J Clin Invest 102:947-957, 1998.

A list of Dr. Sherwin's publications is available via COS.