Mitchell A. Lazar, MD, PhD
Willard and Rhoda Ware Professor in Diabetes and Metabolic Diseases
Medical Staff, Hospital of the University of Pennsylvania
Director, Penn Diabetes Research Center
Founding Director, Institute for Diabetes, Obesity and Metabolism
Director, Cox Institute for Medical Research
Chair, Center and Institute Directors Forum, Perelman School of Medicine
Department: Medicine
Graduate Group Affiliations
Contact information
12-102 Smilow Center for Translational Research
3400 Civic Center Boulevard / 5160
Philadelphia, PA 19104-5160
3400 Civic Center Boulevard / 5160
Philadelphia, PA 19104-5160
Office: (215) 898-0198
Fax: (215) 898-5408
Fax: (215) 898-5408
Email:
lazar@pennmedicine.upenn.edu
lazar@pennmedicine.upenn.edu
Publications
Links
Search PubMed for articles
Institute for Diabetes, Obesity and Metabolism
Lazar Lab
Cell and Molecular Biology Graduate Group
Pharmacological Sciences Graduate Group
Search PubMed for articles
Institute for Diabetes, Obesity and Metabolism
Lazar Lab
Cell and Molecular Biology Graduate Group
Pharmacological Sciences Graduate Group
Education:
S.B. (Chemistry)
Massachusetts Institute of Technology, 1976.
Ph.D. (Neuroscience)
Stanford Univerity, 1981.
M.D.
Stanford Univerity, 1982.
Permanent linkS.B. (Chemistry)
Massachusetts Institute of Technology, 1976.
Ph.D. (Neuroscience)
Stanford Univerity, 1981.
M.D.
Stanford Univerity, 1982.
Description of Research Expertise
Research InterestsEpigenomic regulation of transcription and metabolism by nuclear receptors; mechanism of obesity-associated insulin resistance and diabetes; circadian regulation of metabolism
Key words: diabetes, endocrinology, epigenomics, nuclear receptors, circadian rhythms
Description of Research
The Lazar laboratory is studying the transcriptional regulation of metabolism. We are particularly focused on the role played by nuclear receptors (NRs). In the absence of ligand, NRs bind to DNA and function as potent transcriptional repressors by recruiting corepressor complexes that include the chromatin modulating enzyme histone deacetylase 3 (HDAC3). We are studying the tissue-specific and physiological roles of the corepressor complexes using by combining genomic, genetic, proteomic, bioinformatic, and metabolic phenotyping approaches. We are especially interested in the circadian NR Rev-erb alpha, which utilizes the corepressor complex to potently repress transcription. Rev-erb alpha is a key repressive component of the circadian clock that coordinates metabolism and biological rhythms. We are also studying PPAR gamma, a nuclear receptor that is a master regulator of adipocyte (fat cell) differentiation. Ligands for PPAR gamma have potent antidiabetic activity, and thus PPAR gamma represents a key transcriptional link between obesity and diabetes. The molecular, cellular, and integrative biology of these factors are being studied in mice and humans. We also have discovered resistin, a novel hormone and target of PPAR gamma that is made by fat cells in rodents and by macrophages in humans, and are testing the hypothesis that resistin links metabolism to inflammation in human metabolic diseases.
Rotation Projects for 2021-2022
There are numerous potential projects that I would be pleased to discuss in person.
Lab personnel:
Amy Hauck, Ph.D., (Post-doc)
Yang Xiao, Ph.D., (Post-doc)
Kun Zhu, Ph.D., (Post-doc)
Lauren Woodie, Ph.D., (Post-doc)
Michael Tackenberg, Ph.D., (Post-doc)
Shin-Ichi Inoue, Ph.D., (Post-doc)
Tiffany Fleet, M.D., Ph.D., (Post-doc)
Yoon Jeong Park, Ph.D., (Post-doc)
Rashid Mehmood, Ph.D., (Post-doc)
Mohit Midha, Ph.D., (Post-doc)
Delaine Zayas-Bazan Burgos (Graduate Student)
Isaac Celwyn (Research Specialist)
Maria Krieg (Research Specialist)
Lily Melink (Research Specialist)
Yifan Liu (Research Specialist)
Michelle Burrows (Lab Manager)
Selected Publications
The time is now: accounting for time-of-day effects to improve reproducibility and translation of metabolism research.: Deota S, Pendergast JS, Kolthur-Seetharam U, Esser KA, Gachon F, Asher G, Dibner C, Benitah SA, Escobar C, Muoio DM, Zhang EE, Hotamışlıgil GS, Bass J, Takahashi JS, Rabinowitz JD, Lamia KA, de Cabo R, Kajimura S, Longo VD, Xu Y, Lazar MA, Verdin E, Zierath JR, Auwerx J, Drucker DJ, Panda S. Nat Metab 7(3): 454-468, Mar 2025.Woodie LN, Alberto AJ, Krusen BM, Melink LC, Lazar MA. : Genetic synchronization of the brain and liver molecular clocks defend against chrono-metabolic disease. Proc Natl Acad Sci U S A. 121(51): e2417678121, Dec 2024.
Woodie LN, Melink LC, Midha M, de Araújo AM, Geisler CE, Alberto AJ, Krusen BM, Zundell DM, de Lartigue G, Hayes MR, Lazar MA. : Hepatic vagal afferents convey clock-dependent signals to regulate circadian food intake. Science 386(6722): :673-677, Nov 2024.
Inoue SI, Emmett MJ, Lim HW, Midha M, Richter HJ, Celwyn IJ, Mehmood R, Chondronikola M, Klein S, Hauck AK, Lazar MA.: Short-term cold exposure induces persistent epigenomic memory in brown fat. Cell Metab. 36(8): 1764-1778, Aug 2024.
Paneru BD, Chini J, McCright SJ, DeMarco N, Miller J, Joannas LD, Henao-Mejia J, Titchenell PM, Merrick DM, Lim HW, Lazar MA, Hill DA.: Myeloid-derived miR-6236 potentiates adipocyte insulin signaling and prevents hyperglycemia during obesity. Nat Commun. 15(1): 5394, Jun 2024.
Hauck AK, Mehmood R, Carpenter BJ, Frankfurter MT, Tackenberg MC, Inoue SI, Krieg MK, Cassim Bawa FN, Midha MK, Zundell DM, Batmanov K, Lazar MA.: Nuclear receptor corepressors non-canonically drive glucocorticoid receptor-dependent activation of hepatic gluconeogenesis. Nat Metab. 6(5): 825-836, May 2024.
Woodie LN, Melink LC, Alberto AJ, Burrows M, Fortin SM, Chan CC, Hayes MR, Lazar MA.: Hindbrain REV-ERB nuclear receptors regulate sensitivity to diet- induced obesity and brown adipose tissue pathophysiology. Mol Metab. 79: Article 101861, Jan 2024 Notes: doi: 10.1016/j.molmet.2023.101861.
Woodie LN, Melink LC, Midha M, de Araújo AM, Geisler CE, Alberto AJ, Krusen BM, Zundell DM, de Lartigue G, Hayes MR, Lazar MA.: Hepatic Vagal Afferents Convey Clock-Dependent Signals to Regulate Circadian Food Intake. bioRxiv[Preprint] Dec 2023 Notes: doi: 10.1101/2023.11.30.568080.
Latimer MN, Williams LJ, Shanmugan G, Carpenter BJ, Lazar MA, Dierickx P, Young ME. : Cardiomyocyte-specific disruption of the circadian BMAL1-REV-ERBα/β regulatory network impacts distinct miRNA species in the murine heart. Commun Biol 6(1): 1149, Nov 2023 Notes: doi: 10.1038/s42003-023-05537-z.
Zhu K, Celwyn IJ, Guan D, Xiao Y, Wang X, Hu W, Jiang C, Cheng L, Casellas R, Lazar MA.: An intrinsically disordered region controlling condensation of a circadian clock component and rhythmic transcription in the liver. Mol Cell. 83(19): 3457-3469.e7, Oct 2023 Notes: doi: 10.1016/j.molcel.2023.09.010.