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Mitchell A. Lazar, MD, PhD
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Willard and Rhoda Ware Professor in Diabetes and Metabolic Diseases
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Medical Staff, Hospital of the University of Pennsylvania
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Director, Penn Diabetes Research Center
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Founding Director, Institute for Diabetes, Obesity and Metabolism
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Director, Cox Institute for Medical Research
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Chair, Center and Institute Directors Forum, Perelman School of Medicine
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Department: Medicine
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Graduate Group Affiliations
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Contact information
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12-102 Smilow Center for Translational Research
4a 3400 Civic Center Boulevard / 5160
Philadelphia, PA 19104-5160
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4a 3400 Civic Center Boulevard / 5160
Philadelphia, PA 19104-5160
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Office: (215) 898-0198
34 Fax: (215) 898-5408
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34 Fax: (215) 898-5408
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Email:
lazar@pennmedicine.upenn.edu
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lazar@pennmedicine.upenn.edu
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Publications
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Links
97 Search PubMed for articles
45 Cell and Molecular Biology Graduate Group
56 Lazar Lab
40 Pharmacological Sciences Graduate Group
77 Institute for Diabetes, Obesity and Metabolism
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97 Search PubMed for articles
45 Cell and Molecular Biology Graduate Group
56 Lazar Lab
40 Pharmacological Sciences Graduate Group
77 Institute for Diabetes, Obesity and Metabolism
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Education:
21 9 S.B. 16 (Chemistry) c
3e Massachusetts Institute of Technology, 1976.
21 a Ph.D. 19 (Neuroscience) c
2b Stanford Univerity, 1981.
21 9 M.D. c
2b Stanford Univerity, 1982.
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Permanent link21 9 S.B. 16 (Chemistry) c
3e Massachusetts Institute of Technology, 1976.
21 a Ph.D. 19 (Neuroscience) c
2b Stanford Univerity, 1981.
21 9 M.D. c
2b Stanford Univerity, 1982.
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b7 Epigenomic regulation of transcription and metabolism by nuclear receptors; mechanism of obesity-associated insulin resistance and diabetes; circadian regulation of metabolism
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64 Key words: diabetes, endocrinology, epigenomics, nuclear receptors, circadian rhythms
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26 Description of Research
597 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.
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2f Rotation Projects for 2021-2022
5b There are numerous potential projects that I would be pleased to discuss in person.
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1e Lab personnel:
24 Amy Hauck, Ph.D., (Post-doc)
24 Yang Xiao, Ph.D., (Post-doc)
22 Kun Zhu, Ph.D., (Post-doc)
28 Lauren Woodie, Ph.D., (Post-doc)
2d Michael Tackenberg, Ph.D., (Post-doc)
2a Shin-Ichi Inoue, Ph.D., (Post-doc)
2e Tiffany Fleet, M.D., Ph.D., (Post-doc)
2a Yoon Jeong Park, Ph.D., (Post-doc)
29 Rashid Mehmood, Ph.D., (Post-doc)
26 Mohit Midha, Ph.D., (Post-doc)
35 Delaine Zayas-Bazan Burgos (Graduate Student)
2a Isaac Celwyn (Research Specialist)
29 Maria Krieg (Research Specialist)
29 Lily Melink (Research Specialist)
27 Yifan Liu (Research Specialist)
25 Michelle Burrows (Lab Manager)
26 29
27
Description of Research Expertise
2a Research Interestsb7 Epigenomic regulation of transcription and metabolism by nuclear receptors; mechanism of obesity-associated insulin resistance and diabetes; circadian regulation of metabolism
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64 Key words: diabetes, endocrinology, epigenomics, nuclear receptors, circadian rhythms
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26 Description of Research
597 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.
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2f Rotation Projects for 2021-2022
5b There are numerous potential projects that I would be pleased to discuss in person.
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1e Lab personnel:
24 Amy Hauck, Ph.D., (Post-doc)
24 Yang Xiao, Ph.D., (Post-doc)
22 Kun Zhu, Ph.D., (Post-doc)
28 Lauren Woodie, Ph.D., (Post-doc)
2d Michael Tackenberg, Ph.D., (Post-doc)
2a Shin-Ichi Inoue, Ph.D., (Post-doc)
2e Tiffany Fleet, M.D., Ph.D., (Post-doc)
2a Yoon Jeong Park, Ph.D., (Post-doc)
29 Rashid Mehmood, Ph.D., (Post-doc)
26 Mohit Midha, Ph.D., (Post-doc)
35 Delaine Zayas-Bazan Burgos (Graduate Student)
2a Isaac Celwyn (Research Specialist)
29 Maria Krieg (Research Specialist)
29 Lily Melink (Research Specialist)
27 Yifan Liu (Research Specialist)
25 Michelle Burrows (Lab Manager)
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1a5 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.
72 Bhattarai B, Antonova AU, Fachi JL, Hopkins LS, McCullen MVD, Saini A, 9f 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 9d sustaining epigenetic configuration of RORγt. Nat Immunol. Aug 2025 Notes: doi: 10.1038/s41590-025-02240-5. Online ahead of print.
75 Deota S, Pendergast JS, Kolthur-Seetharam U, Esser KA, Gachon F, Asher G, 197 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.
124 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.
78 Woodie LN, Melink LC, Midha M, de Araújo AM, Geisler CE, Alberto AJ, Krusen 55 BM, Zundell DM, de Lartigue G, Hayes MR, Lazar MA. : Hepatic vagal afferents 80 convey clock-dependent signals to regulate circadian food intake. Science 386(6722): :673-677, Nov 2024.
73 Inoue SI, Emmett MJ, Lim HW, Midha M, Richter HJ, Celwyn IJ, Mehmood R, c2 Chondronikola M, Klein S, Hauck AK, Lazar MA.: Short-term cold exposure induces persistent epigenomic memory in brown fat. Cell Metab. 36(8): 1764-1778, Aug 2024.
160 Paneru BD, Chini J, McCright SJ, DeMarco N, Miller J, Joannas LD, Henao-Mejia J, Titchenell PM, Merrick DM, Lim HW, Lazar MA, Hill DA.: Myeloid-derived miR-6236 potentiates adipocyte insulin signaling and prevents hyperglycemia during obesity. Nat Commun. 15(1): 5394, Jun 2024.
77 Hauck AK, Mehmood R, Carpenter BJ, Frankfurter MT, Tackenberg MC, Inoue SI, 107 Krieg MK, Cassim Bawa FN, Midha MK, Zundell DM, Batmanov K, Lazar MA.: Nuclear receptor corepressors non-canonically drive glucocorticoid receptor-dependent activation of hepatic gluconeogenesis. Nat Metab. 6(5): 825-836, May 2024.
76 Woodie LN, Melink LC, Alberto AJ, Burrows M, Fortin SM, Chan CC, Hayes MR, 55 Lazar MA.: Hindbrain REV-ERB nuclear receptors regulate sensitivity to diet- a4 induced obesity and brown adipose tissue pathophysiology. Mol Metab. 79: Article 101861, Jan 2024 Notes: doi: 10.1016/j.molmet.2023.101861.
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Selected Publications
185 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. Sep 2025 Notes: doi: 10.1038/s43587-025-00950-x. Online ahead of print.1a5 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.
72 Bhattarai B, Antonova AU, Fachi JL, Hopkins LS, McCullen MVD, Saini A, 9f 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 9d sustaining epigenetic configuration of RORγt. Nat Immunol. Aug 2025 Notes: doi: 10.1038/s41590-025-02240-5. Online ahead of print.
75 Deota S, Pendergast JS, Kolthur-Seetharam U, Esser KA, Gachon F, Asher G, 197 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.
124 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.
78 Woodie LN, Melink LC, Midha M, de Araújo AM, Geisler CE, Alberto AJ, Krusen 55 BM, Zundell DM, de Lartigue G, Hayes MR, Lazar MA. : Hepatic vagal afferents 80 convey clock-dependent signals to regulate circadian food intake. Science 386(6722): :673-677, Nov 2024.
73 Inoue SI, Emmett MJ, Lim HW, Midha M, Richter HJ, Celwyn IJ, Mehmood R, c2 Chondronikola M, Klein S, Hauck AK, Lazar MA.: Short-term cold exposure induces persistent epigenomic memory in brown fat. Cell Metab. 36(8): 1764-1778, Aug 2024.
160 Paneru BD, Chini J, McCright SJ, DeMarco N, Miller J, Joannas LD, Henao-Mejia J, Titchenell PM, Merrick DM, Lim HW, Lazar MA, Hill DA.: Myeloid-derived miR-6236 potentiates adipocyte insulin signaling and prevents hyperglycemia during obesity. Nat Commun. 15(1): 5394, Jun 2024.
77 Hauck AK, Mehmood R, Carpenter BJ, Frankfurter MT, Tackenberg MC, Inoue SI, 107 Krieg MK, Cassim Bawa FN, Midha MK, Zundell DM, Batmanov K, Lazar MA.: Nuclear receptor corepressors non-canonically drive glucocorticoid receptor-dependent activation of hepatic gluconeogenesis. Nat Metab. 6(5): 825-836, May 2024.
76 Woodie LN, Melink LC, Alberto AJ, Burrows M, Fortin SM, Chan CC, Hayes MR, 55 Lazar MA.: Hindbrain REV-ERB nuclear receptors regulate sensitivity to diet- a4 induced obesity and brown adipose tissue pathophysiology. Mol Metab. 79: Article 101861, Jan 2024 Notes: doi: 10.1016/j.molmet.2023.101861.
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