Mitchell A. Lazar
University of Pennsylvania
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Primary Section: 42, Medical Physiology and Metabolism Membership Type:
Member
(elected 2017)
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Biosketch
Dr. Mitchell Lazar received an SB degree in Chemistry from MIT, and his MD and PhD from Stanford University. He trained in Internal Medicine at Brigham and Women’s Hospital and in Endocrinology at MGH, then joined the faculty of the University of Pennsylvania where he served for 24 years as Chief of the Division of Endocrinology, Diabetes, and Metabolism, and was Founding Director of Penn's Institute for Diabetes, Obesity, and Metabolism. Lazar has made fundamental discoveries in the nuclear receptor field, and pioneered a systems approach to physiology that combines genetic and environmental manipulations with functional genomics and metabolic phenotyping, leading to new concepts bridging the epigenome, circadian rhythms, and metabolic diseases including diabetes and obesity. His discoveries include the circadian nuclear receptor REV-ERB and its functional interactions with corepressors linking circadian rhythms to metabolism, the endocrine hormone resistin, and the functions of nuclear receptor PPARg in adipocytes. He has delivered many named lectures, and received major awards from a number of international societies and academic institutions. He is also past president of the Association of American Physicians and an elected member of the National Academy of Medicine and the American Academy of Arts and Sciences.
Research Interests
Dr. Mitch Lazar has made fundamental discoveries in the nuclear receptor field, and in understanding the transcriptional regulation of circadian rhythms and metabolism. He pioneered a systems approach to physiology utilizing in vivo functional genomics and metabolic phenotyping to assess the effects of genetic and environmental perturbations on epigenome, circadian rhythms, and metabolic diseases including diabetes and obesity. His discoveries include the circadian nuclear receptor REV-ERB, its functional interactions with corepressors, and control of cell-type specific circadian and metabolic processes. Lazar's work has also linked the fat-specific nuclear receptor PPARg to obesity and diabetes. He showed that PPARg activity regulates insulin sensitivity, and controls the production of resistin, a hormone he discovered as a target of PPARg. Lazar was first to characterize the landscape of PPARg binding to the adipocyte genome, and demonstrated that natural genetic variation regulates PPARg binding and function in human adipocytes and patients. These findings have blazed a trail towards personalizing therapies for metabolic diseases.
