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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 employed by Penn Medicine.

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Clinical Specialties

Specialty:

  • Endocrinology

Programs & Centers:

Board Certification:

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

Clinical Expertise:

  • Thyroid Cancer

Practice Locations and Appointments

Insurance Accepted

  • Aetna US Healthcare
  • Amerihealth Caritas
  • Amerihealth Caritas Medicare
  • Cigna
  • Cigna HealthSpring
  • Clover Health Plan
  • 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
  • Keystone First Medicare
  • Multiplan
  • NJ Medicaid
  • NJ Qualcare
  • Oxford Health Plan
  • PA Health and Wellness (Centene) Medicare
  • 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
  • Veterans Choice Program

Education and Training

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

Memberships

American Academy of Arts and Sciences, National American Association for the Advancement of Science, National American Diabetes Association, National American Federation of Medical Research, National American Society for Clinical Investigation, National American Thyroid Association, National Association of American Physicians, National Eli Lilly, National Institute of Medicine, National National Academy of Sciences, National Searle Scholars Program, National The Endocrine Society, National

Hospital Affiliation

Dr. Lazar is employed by Penn Medicine.

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 2017-2018
There are numerous potential projects that I would be pleased to discuss in person.

Lab personnel:
David Steger, Ph.D. (Research Assistant Professor)
Victoria Nelson, Ph.D. (Post-doc)
Dongyin Guan, Ph.D. (Post-doc)
David Hill, M.D., Ph.D. (Post-doc)
Marine Adlanmerini, Ph.D. (Post-doc)
Wenxiang Hu, Ph.D. (Post-doc)
Yehuda Shabtai, Ph.D. (Post-doc)
Pieterjan Dierickx, Ph.D., (Post-doc)
Chunjie Jiang, Ph.D., (Post-doc)
Yong Hoon Kim (Graduate Student)
Hannah Richter (Graduate Student)
Erika Briggs (Research Specialist)
Lindsey Peed (Research Specialist)
Kavya Chgireddy (Bioinformatics Research Specialist)
Wesley Ho (Research Specialist)
Ying Xiong (Research Specialist)
Joe Weaver (Lab Manager)


Selected Publications:

Guan D, Xiong Y, Borck PC, Jang C, Doulias PT, Papazyan R, Fang B, Jiang C, Zhang Y, Briggs ER, Hu W, Steger D, Ischiropoulos H, Rabinowitz JD, Lazar MA.: Diet-Induced Circadian Enhancer Remodeling Synchronizes Opposing Hepatic Lipid Metabolic Processes. Cell. 174 (4): 831-842.e12,2018.

Nelson VL, Nguyen HCB, Garcìa-Cañaveras JC, Briggs ER, Ho WY, DiSpirito JR, Marinis JM, Hill DA, Lazar MA.: PPARγ is a nexus controlling alternative activation of macrophages via glutamine metabolism. Genes Dev. 32 (15-16): 1035-1044,2018.

Zhang Y, Dallner OS, Nakadai T, Fayzikhodjaeva G, Lu YH, Lazar MA, Roeder RG, , Friedman JM.: A noncanonical PPARγ/RXRα-binding sequence regulates leptin expression in response to changes in adipose tissue mass. Proc Natl Acad Sci U S A [Epub ahead of print] : 2018.

Lazar MA.: Reversing the curse on PPARγ. J Clin Invest 128 (6): 2202-2204,2018.

Razzoli M, Emmett MJ, Lazar MA, Bartolomucci A.: β-Adrenergic receptors control brown adipose UCP-1 tone and cold response without affecting its circadian rhythmicity. FASEB J. [Epub ahead of print] : 2018.

Borck PC, Batista TM, Vettorazzi JF, Soares GM, Lubaczeuski C, Guan D, Boschero AC, Vieira E, Lazar MA, Carneiro EM.: Nighttime light exposure enhances Rev-erbα-targeting microRNAs and contributes to hepatic steatosis. Metabolism 85 : 250-258,2018.

Hill DA, Lim HW, Kim YH, Ho WY, Foong YH, Nelson VL, Nguyen HCB, Chegireddy K, Kim J, Habertheuer A, Vallabhajosyula P, Kambayashi T, Won KJ, Lazar MA.: Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue. Proc Natl Acad Sci U S A. 115 (22): E5096-E5105,2018.

Kim YH, Marhon SA, Zhang Y, Steger DJ, Won KJ, Lazar MA.: Rev-erbα dynamically modulates chromatin looping to control circadian gene transcription. Science 359 (6381): 1274-1277,2018.

Jang JC, Li J, Gambini L, Batugedara HM, Sati S, Lazar MA, Fan L, Pellecchia, M, Nair MG: Human resistin protects against endotoxic shock by blocking LPS-TLR4 interaction. Proc Natl Acad Sci U S A 114 (48): E10399-E10408,2017.

Poleshko A, Shah PP, Gupta M, Babu A, Morley MP, Manderfield LJ, Ifkovits JL, , Calderon D, Aghajanian H, Sierra-Pagán JE, Sun Z, Wang Q, Li L, Dubois NC, Morrisey EE, Lazar MA, Smith CL, Epstein JA, Jain R.: Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction. Cell 171 (3): 573-587,2017.

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
Patient appointments: 800-789-7366 (PENN)

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