Endocrinologist and physician-scientist Dr. Mitch Lazar, known for his discovery of the hormone resistin and his contributions to the transcriptional regulation of circadian rhythms and metabolism, will deliver an Apex Lecture on Tuesday, Feb. 11, at 3:00 p.m. in 1220 MRB III. A reception will follow the lecture at 4:00 p.m. in the MRB III first-floor atrium. The title of his talk is “Nuclear Receptors and the Circadian Regulation of Metabolism.” This School of Medicine Basic Sciences Apex Lecture is co-sponsored by the Department of Molecular Physiology and Biophysics.
Lazar is the Willard and Rhoda Ware Professor of Diabetes and Metabolic Diseases and director of the Institute for Diabetes, Obesity and Metabolism at the University of Pennsylvania Perelman School of Medicine. His groundbreaking research has focused on circadian rhythms and metabolism, and he has made fundamental contributions to the fields of endocrinology, diabetes, and chronobiology. Lazar discovered the circadian nuclear receptor REV-ERB and its heme ligand, transcriptional repression, and interactions with corepressors and histone deacetylases. His work has demonstrated the fundamental importance of REV-ERBs and their corepressor complex in the physiology of circadian rhythms and organismal metabolism.
Lazar also discovered that another nuclear receptor, PPARγ, is predominantly expressed in adipocytes and pioneered the linkage of PPARγ to adipocyte differentiation, insulin resistance, and type 2 diabetes. He led the way to a genome-wide understanding of PPARγ function and discovered resistin as a novel adipocyte hormone that impairs insulin action. resistin is the first member of a previously unknown family of secreted resistin-like molecules.
The Lazar lab studies the transcriptional regulation of metabolism. Metabolic diseases, including diabetes and obesity, have a strong genetic basis, yet their increasing prevalence has been fueled by an environment replete with fattening diets, insufficient physical activity, and exposure to light around the clock. The lab’s goals are to understand the molecular mechanisms underlying circadian and metabolic physiology and how these contribute to homeostasis, but also how they may be overcome by harmful environmental factorsthat could lead to metabolic diseases.
Lazar has pioneered a systems approach to physiology that combines state-of-the-art in vivo “omics” with genetic and environmental manipulations and detailed metabolic phenotyping. This approach has had a major impact on our current understanding of the pathophysiology of obesity and diabetes, leading to new concepts linking the epigenome to metabolism and stimulating novel translational approaches for the treatment and prevention of metabolic diseases.
Lazar has served as a member of the Board of Scientific Councilors of the National Institute of Diabetes and Digestive and Kidney Diseases as well as many editorial and scientific advisory boards. He has been elected to the American Society for Clinical Investigation cand the Association of American Physicians and their respective councils, and served as president of the AAP Council in 2020–2021. He has received numerous awards from international societies and universities, including the Stanley J. Korsmeyer Award from the ASCI, the Transatlantic Medal from the Society for Endocrinology, the Roy Luft Award from the Karolinska Institute, the Keith Harrison Memorial Lectureship from the Endocrine Society of Australia, and the Fred Conrad Koch Lifetime Achievement Award from the Endocrine Society. He also received the 2025 George M. Kober Medal from the AAP for his pioneering and enduring, impactful contributions to improve health. Lazar is an elected member of the National Academy of Medicine, the American Academy of Arts and Sciences, and the National Academy of Science.
Lecture abstract
Circadian rhythms are an inherent feature of mammalian physiology, controlled by molecular clocks comprising transcriptional and translational feedback loops that have evolved to anticipate the 24-hour light-dark cycle on Earth. Environmental challenges such as shiftwork or jetlag are detrimental to metabolic health, but how desynchronous signals are transmitted among tissues is not well understood. REV-ERB nuclear receptors are key components of the molecular clock and a major link between circadian rhythms and metabolism.
We have used conditional deletion strategies to address the role and hierarchies of the molecular clocks in different cells and tissues, focusing on the liver, which is central to systemic metabolism, as well as the body’s master clock, located in the suprachiasmatic nucleus of the hypothalamus. Mice lacking REV-ERBs in hepatocytes exhibit rhythmic changes in lipid metabolism due to cell-autonomous loss of diurnal expression of a subset of liver genes, as well as non-cell-non-autonomous alterations of rhythmic gene expression in other liver cell types. Loss of SCN REV-ERBs leads to a marked shortening of behavioral rhythms and a desynchrony with the 24-hour light-dark cycle that predisposes to metabolic dysfunction, including fatty liver. Unexpectedly, hepatic REV-ERBs also provide feedback to the brain via the vagus nerve to control food intake. Together, the results help explain the metabolic disruption resulting from desynchrony between environmental conditions and endogenous clocks.
About the Apex Lecture Series
There are major inflection points in biomedical discovery that create new fields, new ideas, and new opportunities to impact human health. To engage with global researchers contributing to these inflection points, the Vanderbilt School of Medicine Basic Sciences launched the Apex Lecture Series in 2023. This school-wide seminar series brings scientists who are influencing the trajectory of their fields to engage with our scientific community on campus.