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Mitchell A. Lazar, MD, PhD

Mitchell A. Lazar, MD, PhD Physician

Chief, Endocrinology, Diabetes and Metabolism Division Willard and Rhoda Ware Professor in Diabetes and Metabolic Diseases Professor of Genetics

Dr. Lazar is a Penn Medicine employed physician.

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Clinical Specialties

Specialty:

  • Diabetes, Endocrinology and Metabolism

Programs & Centers:

Board Certification:

  • Endocrinology, Diabetes, & Metabolism, 1987
  • Internal Medicine, 1985

Clinical Expertise:

  • Thyroid Cancer

Practice Locations and Appointments

  • Penn Endocrinology

    Perelman Center for Advanced Medicine West Pavilion, 4th Floor 3400 Civic Center Boulevard Philadelphia, PA 19104 800-789-7366 (PENN)

    A facility of the Hospital of the University of Pennsylvania

Insurance Accepted

  • Aetna US Healthcare
  • Cigna
  • Cigna HealthSpring
  • CVS Health
  • Devon Health Services (Americare)
  • Gateway Health Plan
  • Geisinger Health Plan
  • HealthAmerica / HealthAssurance, a Coventry Plan
  • HealthPartners
  • HealthPartners Medicare
  • HealthSmart
  • Highmark Blue Shield
  • Horizon Blue Cross Blue Shield of New Jersey
  • Humana / Choicecare
  • Independence Blue Cross (Keystone East)
  • Intergroup
  • Keystone First
  • Multiplan
  • NJ Medicaid
  • NJ Qualcare
  • Oxford Health Plan
  • PA Medicaid
  • PA Medicare
  • Preferred Health Care/LGH
  • Rail Road Medicare / Palmetto GBA
  • Remedy Partners at Penn Medicine
  • Tricare
  • United Healthcare
  • UnitedHealthcare Community Plan
  • US Family Health Plan

Education and Training

Medical School: Stanford University School of Medicine
Residency: Brigham and Women's Hospital
Fellowship: Massachusetts General Hospital

Memberships

Abbott Labs, 2001-2006, National American Academy of Arts and Sciences, National American Association for the Advancement of Science, National American Diabetes Association , National American Diabetes Association, National American Diabetes Association, National American Federation of Medical Research, National American Society for Clinical Investigation, National American Society for Clinical Investigation, National American Thyroid Association , National American Thyroid Association, National American Thyroid Association, National American Thyroid Association, National Amylin, National Association of American Physicians, National Dr. Reddy’s Pharmaceutical Company, National Eli Lilly, National Federation of American Societies for Experimental Biology (FASEB) , National Genaera Corporation, National HHMI, National Institute of Medicine, National Knoll/Abbott, National National Diabetes and Digestive and Kidney Diseases, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National NIH, National Novartis, National Philadelphia Ventures, Local Searle Scholars Program, National The Endocrine Society, National Wyeth Women's Health and Musculoskeletal Biology, National

Hospital Affiliation

Dr. Lazar is a Penn Medicine employed physician.

Hospital Privileges:

  • Hospital of the University of Pennsylvania: Has privileges to treat patients in the hospital.

Research

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 2016-2017
There are numerous potential projects that I would be pleased to discuss in person.

Lab personnel:
David Steger, Ph.D. (Research Assistant Professor)
Sean Armour, Ph.D. (Post-doc)
Romeo Papazyan, Ph.D. (Post-doc)
Victoria Nelson, Ph.D. (Post-doc)
Paul Titchenell, Ph.D. (Post-doc)
Dongyin Guan, Ph.D. (Post-doc)
David Hill, M.D., Ph.D. (Post-doc)
Zhenghui Li, Ph.D. (Post-doc)
Marine Adlanmerini, Ph.D. (Post-doc)
Wenxiang Hu, Ph.D. (Post-doc)
Matthew Emmett (Graduate Student)
Jarrett Remsberg (Graduate Student)
Yuxiang Zhang (Graduate Student)
Yong Hoon Kim (Graduate Student)
Patricia Borck (Graduate Student)
Erika Briggs (Research Specialist)
Lindsey Peed(Research Specialist)
Manashree Damle (Bioinformatics Research Specialist)
Yee Hoon Foong (Research Specialist)
Wesley Ho (Research Specialist)
Joe Weaver (Lab Manager)

Selected Publications:

Hong S, Zhou W, Fang B, Lu W, Loro E, Damle M, Ding G, Jager J, Zhang S, Zhang Y, Feng D, Chu Q, Dill BD, Molina H, Khurana TS, Rabinowitz JD, Lazar MA, Sun Z.: Dissociation of muscle insulin sensitivity from exercise endurance in mice by HDAC3 depletion. Nature Medicine : 2016.

Papazyan R, Sun Z, Kim YH, Titchenell PM, Hill DA, Lu W, Damle M, Wan M, Zhang Y, Briggs ER, Rabinowitz JD, Lazar MA.: Physiological Suppression of Lipotoxic Liver Damage by Complementary Actions of HDAC3 and SCAP/SREBP. Cell Metab. : 2016.

Bass J, Lazar MA.: Circadian time signatures of fitness and disease. Science 354 (6315): 994-999,2016.

Teng X, Emmett MJ, Lazar MA, Goldberg E, Rabinowitz JD.: Lactate Dehydrogenase C Produces S-2-Hydroxyglutarate in Mouse Testis. ACS Chem Biol. 11 (9): 2420-7,2016.

Ferrannini G, Namwanje M, Fang B, Damle D, Li D, Liu Q, Lazar MA, Qiang L.: Genetic background determine brown remodeling of white fat in rodents. Molecular Metabolism 5 (10): 948-958,2016.

Zhang Y, Fang B, Damle M, Guan D, Li Z, Kim YH, Gannon M, Lazar MA.: HNF6 and Rev-erbα integrate hepatic lipid metabolism by overlapping and distinct transcriptional mechanisms. Genes Dev. 30 (14): 1636-44,2016.

Zhang L, He X, Liu L, Jiang M, Zhao C, Wang H, He D, Zheng T, Zhou X, Hassan A, Ma Z, Xin M, Sun Z, Lazar MA, Goldman SA, Olson EN, Richard Lu Q.: Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch. Dev Cell. 37 (6): doi: 10.1016/j.devcel.2016.06.004.,2016.

Jager J, Wang F, Fang B, Lim HW, Peed LC, Steger DJ, Won KJ, Kharitonenkov A, Adams AC, Lazar MA.: The Nuclear Receptor Rev-erbα Regulates Adipose Tissue-Specific Fibroblast Growth Factor 21 (FGF21) Signaling. J Biol Chem. 291 (20): 10867-75,2016.

Wang Y, Frank DB, Morley MP, Zhou S, Wang X, Lu MM, Lazar MA, Morrisey EE.: HDAC3-Dependent Epigenetic Pathway Controls Lung Alveolar Epithelial Cell Remodeling and Spreading via miR-17-92 and TGF-β Signaling Regulation. Dev Cell 36 (3): 303-15,2016.

Zhang L, He X, Liu L, Jiang M, Zhao C, Wang H, He D, Zheng T, Zhou X, Hassan A, Ma Z, Xin M, Sun Z, Lazar MA, Goldman SA, Olson EN, Lu QR.: Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch. Dev Cell 36 (3): 316-30,2016.

View all publications

Academic Contact Info

12-102 Smilow Center for Translational Research
3400 Civic Center Boulevard / 5160

Philadelphia, PA 19104-5160
Phone: (215) 898-0198
Fax: (215) 898-5408
Patient appointments: 800-789-7366 (PENN)

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