Department of Medicine

Endocrinology, Diabetes & Metabolism Faculty

Michael Clare-Salzler, M.D.
Division Chief, Department of Pathology
Immunology & Laboratory Medicine

Professional Summary

Dr. Clare-Salzler received his M.D. degree in 1979 from the State University of New York at Buffalo. He also completed his residency training in Internal Medicine at SUNY Buffalo. He was a research fellow in endocrinology at the University of California Los Angeles where he studied the immunology of islet transplantation and the immunopathogenesis of type 1 diabetes in NOD mice. Dr. Clare-Salzler was an Assistant Professor of Medicine at UCLA from 1988-1993 and was Director of the UCLA Adult Diabetes Program during this period. In 1993 Dr. Clare-Salzler became a member of the Departments of Pathology, Immunology and Laboratory Medicine, Internal Medicine and Surgery at the University of Florida where he is currently an Associate Professor and Associate Director of Research Affairs for Pathology. He is also the Director of the Advanced Immunology Concentration the College of Medicine Graduate Program.

Clinical Interests and Activities

Dr. Clare-Salzler‘s areas of clinical expertise lie in the diagnosis and management of type 1 diabetes, autoimmune thyroid disease, management of thyroid nodules, fine aspiration of thyroid nodules and thyroid cancer. He is also well versed in other endocrine diseases including Cushing’s Disease, pituitary disease, pheochromocytoma, adrenal tumors and parathyroid diseases.

Dr. Clare-Salzler is also member of the NIH funded International Multi-Center diabetes prevention trial, the Diabetes Prevention Trial for type 1 diabetes or DPT-1. He is also an investigator on other diabetes screening programs at the University of Florida including the infant screening program PANDA.

Laboratory Research Summary

The overall goal of Dr. Clare-Salzler’s NIH and Juvenile Diabetes Research Foundation funded research is to define the immunopathogenic mechanisms that lead cause type-1 diabetes. It is hoped that these studies will lead to methods of early detection and disease prevention of this disease. To accomplish these goals we study immune cells from the non obese diabetic (NOD) mouse and from humans with a defined high-risk for type-1 diabetes. We have focused many of our studies on the biology of antigen presenting cell populations, e.g. macrophages and dendritic cells and are defining their roles in autoimmunity and tolerance. Studies to date indicate that dendritic cells presenting islet antigens impart tolerance and block the development of autoimmune disease in the NOD mouse. Other studies indicate defects in myeloid cells, including monocytes, macrophages, and myeloid dendritic cells contribute to the pathogenesis of this disease. In addition, studies in the laboratory have defined defects in activation induced cell death, a critical mechanism of peripheral tolerance, in both NOD mice and in humans with a risk for type-1 diabetes. To determine the genetic contributions to the immunophenotypes described above we examine these in congenic mice with defined regions of NOD chromosomes on the C57BL/6 background. This analysis allows one to determination which regions NOD chromosomes controls the immunophenotype, e.g. defective deletional tolerance. Using this approach the laboratory defined an abnormal expression of cyclooxygenase 2 (Cox 2) in monocytes and macrophages which leads to heightened prostaglandin metabolism in the NOD mouse and also in humans who are at risk for type-1 diabetes. Analysis of Cox 2 in macrophages of congenic mice indicates that this phenotype is controlled by genes from a region of mouse chromosome 1. The generation of new congenic strains with shorter intervals will allow for eventual identification of the genes responsible for this phenotype by positional cloning. The same approach has also defined two regions of the NOD genome that contribute to the defects in deletional tolerance, one in a region on mouse chromosome 17, perhaps the MHC or a gene(s) within this region, and another contained on chromosome 1. We have also determined that a region of chromosome 3 of the mouse contributes to defective myeloid cell differentiation in the NOD mouse.

The long range goal of these projects is to define key defects in the immune response and the genes responsible for these. With this knowledge, methods will be developed to inhibit or block the development of autoimmunity against the insulin producing cell and prevent type 1 diabetes.

In addition to the aforementioned research areas Dr. Clare-Salzler’s laboratory is investigating the role of antigen presenting defects in autoimmune thyroid disease, the genetic defects in TNF- signaling in the NOD mouse, gene therapy for the treatment of inflammatory diseases such as sepsis and the biology of dendritic cells and their use as cellular therapeutic agents.