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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:

  • Abnormal Glucose Metabolism
  • Achondroplasia
  • Addison's Disease
  • Adrenal Adenoma
  • Adrenal Gland Disorders
  • Adrenal Mass
  • Adrenal Nodules
  • Adrenogenital Syndrome
  • Androgen Excess
  • Androgen Insensitivity
  • Calcium Metabolism
  • Carcinoid Syndrome
  • Chronic Thyroiditis (Hashimoto's Disease)
  • Congenital Adrenal Hyperplasia
  • Congenital Hypothyroidism
  • Conn Syndrome
  • Cushing's Disease
  • Diabetes
  • Diabetes Education
  • Disorders of Sexual Differentiation
  • Ectopic Hyperparathyroidism
  • Endocrine Disorders
  • Familial Hyperparathyroidism
  • Familial Hypocalciuric Hypercalcemia
  • Feminizing Syndrome
  • Glucagonoma
  • Glucocorticoid Deficiency
  • Goiter
  • Graves' Disease
  • Growth Disorders
  • Growth Hormone Abnormalities
  • Gynecomastia
  • Hyperaldosteronism
  • Hypercalcemia
  • Hyperglycemia
  • Hyperparathyroidism
  • Hyperthyroidism (Overactive Thyroid)
  • Hypocalcemia
  • Hypoglycemia
  • Hypogonadism
  • Hypoparathyroidism
  • Hypopituitarism
  • Hypothalamic-Pituitary Disorder
  • Hypothyroidism (Underactive Thyroid)
  • Insulin Pump
  • Insulin Resistance
  • Insulinoma
  • Metabolic Bone Diseases
  • Metabolic Syndrome
  • Moon Facies
  • Multiple Endocrine Neoplasia
  • Myxedema
  • Nodular Goiter
  • Nontoxic Goiter
  • Osteopenia
  • Osteoporosis
  • Panhypopituitarism
  • Parathyroid Disease
  • Parathyroid Hyperplasia
  • Pheochromocytoma
  • Pituitary Adenoma
  • Pituitary Dwarfism
  • Pituitary Gland Disorders
  • Pituitary Tumors
  • Polyglandular Autoimmune Syndrome
  • Pseudohermaphroditism
  • Pseudohypoparathyroidism
  • Radioactive Iodine (Radioiodine) Therapy
  • Rickets
  • Secondary Hyperaldosteronism
  • Silent Thyroiditis
  • Thyroid Cyst
  • Thyroid Disorders
  • Thyroid Nodule Biopsy
  • Thyroid Nodules
  • Thyrotoxic Exophthalmos
  • Thyrotoxicosis
  • Toxic Diffuse Goiter
  • Toxic Nodular Goiter
  • Type 1 Diabetes
  • Type 2 Diabetes
  • Vitamin D Deficiency
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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)
  • eLAP Services
  • Gateway Health Plan
  • Geisinger Health Plan
  • HealthAmerica / HealthAssurance, a Coventry Plan
  • HealthPartners
  • HealthPartners Medicare
  • HealthSmart
  • Highmark Blue Shield
  • Homestead Smart Health Plans
  • 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
  • Provider Partners Health Plan
  • 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:

Adlanmerini M, Carpenter BJ, Remsberg JR, Aubert Y, Peed LC, Richter HJ, Lazar MA.: Circadian lipid synthesis in brown fat maintains murine body temperature during chronic cold. Proc Natl Acad Sci U S A. 116 (37): 18691-18699,2019.

Kuo T, Kraakman MJ, Damle M, Gill R, Lazar MA, Accili D.: Identification of C2CD4A as a human diabetes susceptibility gene with a role in β cell insulin secretion. Proc Natl Acad Sci U S A. : 2019.

Jaitin DA, Adlung L, Thaiss CA, Weiner A, Li B, Descamps H, Lundgren P, Bleriot C, Liu Z, Deczkowska A, Keren-Shaul H, David E, Zmora N, Eldar SM, Lubezky N, Shibolet O, Hill DA, Lazar MA, Colonna M, Ginhoux F, Shapiro H, Elinav E, Amit I.: Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner. Cell : 2019.

Dierickx P, Emmett MJ, Jiang C, Uehara K, Liu M, Adlanmerini M, Lazar MA.: SR9009 has REV-ERB-independent effects on cell proliferation and metabolism. Proc Natl Acad Sci U S A 116 (25): 12147-12152,2019.

Kuo T, Damle M, González BJ, Egli D, Lazar MA, Accili D.: Induction of α cell-restricted Gc in dedifferentiating β cells contributes to stress-induced β-cell dysfunction. JCI Insight. : 2019.

Dallner OS, Marinis JM, Lu YH, Birsoy K, Werner E, Fayzikhodjaeva G, Dill BD, , Molina H, Moscati A, Kutalik Z, Marques-Vidal P, Kilpeläinen TO, Grarup N, Linneberg A, Zhang Y, Vaughan R, Loos RJF, Lazar MA, Friedman JM.: Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity. Nat Med. 25 (3): 507-516,2019.

Emmett MJ, Lazar MA.: Integrative regulation of physiology by histone deacetylase 3. Nat Rev Mol Cell Biol. 20 (2): 102-115,2019.

Hu W, Jiang C, Guan D, Dierickx P, Zhang R, Moscati A, Nadkarni GN, Steger DJ, Loos RJF, Hu C, Jia W, Soccio RE, Lazar MA.: Patient Adipose Stem Cell-Derived Adipocytes Reveal Genetic Variation that Predicts Antidiabetic Drug Response. Cell Stem Cell. 24 (2): 299-308,2019.

Koerner MV, FitzPatrick L, Selfridge J, Guy J, De Sousa D, Tillotson R, Kerr, A, Sun Z, Lazar MA, Lyst MJ, Bird A.: Toxicity of overexpressed MeCP2 is independent of HDAC3 activity. Genes Dev. 32 ((23-24)): 1514-1524,2018.

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.

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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