Mitchell A. Lazar, MD, PhD
Willard and Rhoda Ware Professor
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
Chini J, DeMarco N, Mitchell DV, McCright SJ, Shen KM, Pandey D, Clement RL, Miller J, Jain R, Taylor DM, Lazar MA, Hill DA.: D9 regulates macrophage-mediated remodeling of adipose tissue in obesity. JCI Insight 11(6): e193837, Feb 2026 Notes: doi: 10.1172/jci.insight.193837.Cassim Bawa FN, Lazar MA. : Nuclear receptor coregulator interactions: beyond the switch. Genes Dev. 40(3-4): 146-159, Feb 2026 Notes: doi: 10.1101/gad.353393.125.
Nadarajah CJ, Li MY, Quillin EI, Boyer K, Dimitry JM, Chen Y, King MW, Saliu IO, Lee J, Sheehan PW, Davis AA, Lazar MA, Zhao G, Musiek ES.: REV-ERB-alpha and -beta coordinately regulate astrocyte reactivity and proteostatic function. Proc Natl Acad Sci U S A. 123(5): e2511093123, Feb 2026 Notes: doi:10.1073/pnas.2511093123.
Lee J, Kang R, Park S, Saliu IO, Son M, Voorhees JR, Dimitry JM, Quillin EI, Woodie LN, Lananna BV, Gan L, Goo YA, Zhao G, Lazar MA, Burris TP, Musiek ES.: REV-ERBα regulates brain NAD+ levels and tauopathy via an NFIL3-CD38 axis. Nat Aging. 5(10): 2070-2085, Oct 2025 Notes: doi: 10.1038/s43587-025-00950-x. Online ahead of print.
Hu W, Zhu B, He N, Xiao Y, Chen B, Li C, Mandla R, Liu Y, Zhang J, Chang X, Yu F, Vujkovic M, Lynch J, Chang KM; VA Million Veteran Program; Pasaniuc B, Rader D, Lazar MA.: Integrative functional genomics reveals transcriptional regulatory function of risk alleles for metabolic liver disease. Res Sq Page: rs.3.rs-6984670, Oct 2025 Notes: doi: 10.21203/rs.3.rs-6984670/v1.
Wang X, Moore MP, Shi H, Xiao Y, Zhang J, Faccioli LAP, Hu Z, Khalid S, Saleheen D, Stupack DG, Kisseleva T, Soto Gutierrez A, Lazar MA, Tabas I. : A non-apoptotic caspase-8-meteorin pathway in hepatocytes promotes MASH fibrosis. Nat Metab. 7(10): 2067-2082, Oct 2025 Notes: doi: 10.1038/s42255-025-01355-1.
Tackenberg MC, Heliodoro KM, Melink LC, Liu Y, Zhu K, Lazar MA. : Normal circadian period length requires repression of Npas2 by REV-ERB nuclear receptors. Cell Rep. 44(10): 116437, Oct 2025 Notes: doi:10.1016/j.celrep.2025.116437.
Bhattarai B, Antonova AU, Fachi JL, Hopkins LS, McCullen MVD, Saini A, Oliveira S, Beatty WL, Musiek ES, Kuchroo VK, Lazar MA, Oltz EM, Colonna M.: Circadian circuits control plasticity of group 3 innate lymphoid cells by sustaining epigenetic configuration of RORγt. Nat Immunol 26(9): 1527-1539, Sep 2025 Notes: doi: 10.1038/s41590-025-02240-5.
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.: The time is now: accounting for time-of-day effects to improve reproducibility and translation of metabolism research. 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.