Faculty

Mitchell A. Lazar, MD, PhD

Willard and Rhoda Ware Professor in Diabetes and Metabolic Diseases

Department: Medicine

Graduate Group Affiliations

Contact information

12-102 Smilow Center for Translational Research
3400 Civic Center Boulevard / 5160
Philadelphia, PA 19104-5160

Office: (215) 898-0198
Fax: (215) 898-5408

Email:
lazar@pennmedicine.upenn.edu

Publications

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Education
S.B. (Chemistry)
Massachusetts Institute of Technology, 1976.
Ph.D. (Neuroscience)
Stanford Univerity, 1981.
M.D.
Stanford Univerity, 1982.

Links
Search PubMed for articles
Cell and Molecular Biology Graduate Group
Pharmacological Sciences Graduate Group
Lazar Lab
Institute for Diabetes, Obesity and Metabolism

Permanent link

> Perelman School of Medicine > Faculty > Details

Description of Research Expertise

Research Interests
Epigenomic 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

Zhou Q, Lazar MA: You are when you eat: How food synchronizes liver clocks. Sci Adv 12(30): eaej7423, Jul 2026 Notes: doi: 10.1126/sciadv.aej7423.

Karavaeva I, Basse AL, Trammell SAJ, Hussain MF, Markussen LK, Havelund JF, Isidor MS, Richter HJ, Chubanava S, Deleye Y, Kaiser Z, Shen Y, Neess D, Sass F, Finger F, Muntadas LA, Tandio D, Ma T, Sustarsic EG, Embring H, Kristensen CK, McIntyre RL, Martinez GJ, Husted AS, Emmett MJ, Kipp ZA, Frost M, Jedrychowski MP, van Weeghel M, Majd H, Zhuravleva E, McGarrah RW, Plucinska K, Midha MK, Prokesch A, Cohen P, Granneman JG, Seale P, Houtkooper RH, Hansen JB, Gygi SP, Schwartz TW, Gillum MP, Hinds TD Jr, Soccio RE, White PJ, Kunji ERS, Moritz T, Treebak JT, Mandrup S, Emanuelli B, Kazak L, Færgeman NJ, Lazar MA, Zachary Gerhart-Hines. : Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of interorganellar lipid cycling. bioRxiv [Preprint] doi: 10.64898/2026.05.30.724257, Jun 2026.

Zhu B, He N, Xiao Y, Chen B, Li C, Mandla R, Liu Y, Zhang J, Chang X, Yu F, Vujkovic M, Lynch JA, Chang KM; VA Million Veteran Program; Pasaniuc B, Rader DJ, Lazar MA, Hu W.: Integrative analyses elucidate transcriptional regulatory functions of risk alleles for metabolic liver disease. Nat Genet 58(6): 1280-1294, Jun 2026 Notes: doi: 10.1038/s41588-026-02617-8.

Welles JE, Garifallou JP, Gonzalez MV, Santoleri D, Choudhury FK, DeNicola GM, Martin RW, Jiang C, Kim J, Li G, Aki Y, Chang CJ, Li D, Wells RG, Xiao Y, Zhang J, Lazar MA, Brady DC, Titchenell PM.: Reduction in Hepatic Phosphatidylcholine Biosynthesis Promotes MASH Through Copper Deficiency. bioRxiv [Preprint] May 2026 Notes: doi:10.64898/2026.05.13.723926.

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.

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.