Mitchell A. Lazar, MD, PhD, is the 2009 recipient of the American Society for Clinical Investigation’s Stanley J. Korsmeyer Award, in recognition of his outstanding contributions to our understanding of the transcriptional regulation of metabolism. Dr. Lazar’s discoveries of several thyroid hormone and orphan nuclear receptors and their gene expression silencing mechanisms have been transformative. His cloning of Rev-erbα led him to a series of seminal discoveries on the mechanism of nuclear receptor-mediated repression. These include the regulation of Rev-erbα by heme ligand and lithium destabilization, the composition of core nuclear receptor corepressor-histone deacetylase complexes, the corepressor “CoRNR” nuclear receptor interaction motif, and the activation of histone deacetylase function by corepressor binding. Dr. Lazar’s recent discovery that the corepressor-deacetylase interaction epigenetically governs metabolism and circadian rhythm proves the physiological importance of the corepressor paradigm. Dr. Lazar has also made pioneering contributions to the linkage of the nuclear receptor PPARγ to adipocyte differentiation, insulin resistance, and type 2 diabetes. In addition, his discovery of resistin as a novel adipocyte hormone that impairs insulin action created a new view of the connection between obesity and insulin resistance.
Dr. Lazar is currently the Sylvan Eisman Professor of Medicine and Genetics at the University of Pennsylvania School of Medicine. He is also Chief of the University of Pennsylvania’s Division of Endocrinology, Diabetes and Metabolism and Director of the Institute for Diabetes, Obesity, and Metabolism. He received his undergraduate degree in chemistry from the Massachusetts Institute of Technology, where he did research on peroxide chemistry in the lab of Prof. Frederick Greene and in photochemistry in the lab of Prof. Nicholas Turro in a summer program at Columbia University. He then went to Stanford Medical School, where he worked on the enzymology of tyrosine hydroxylase in the lab of Prof. Jack Barchas, leading to a Ph.D. in Neuroscience in addition to an M.D. He did an internship and residency in Internal Medicine at Brigham and Women’s Hospital, followed by an endocrinology fellowship at the Massachusetts General Hospital, where he worked on parathyroid hormone secretion in the lab of Prof. Hank Kronenberg. His work on nuclear receptors began with his cloning of novel thyroid and orphan receptors as a post-doctoral fellow in the lab of Prof. Bill Chin at Brigham and Women’s Hospital.
Since joining the faculty at the University of Pennsylvania, Dr. Lazar has been an outstanding mentor whose trainees have advanced to successful careers in academia and industry. He has received numerous honors, including the Van Meter Award of the American Thyroid Association, the Outstanding Investigator Award of the American Federation for Medical Research, the BMS Freedom to Discover Award, and the Richard Weitzman Award and the Edwin B. Astwood Award Lecture from The Endocrine Society. In addition, he received two NIH MERIT awards and is currently a member of the Board of Scientific Councilors of the National Institutes of Diabetes, Digestive, and Kidney Diseases. Dr. Lazar has also been elected to the American Society for Clinical Investigation and its Council, the Association of American Physicians, the Institute of Medicine of the National Academy of Sciences, and the American Academy of Arts and Sciences.
The 2009 ASCI/Stanley J. Korsmeyer Award Chewing the fat with Mitchell A. Lazar in the Journal of Clinical Investigation