MITCHELL LAZAR

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc The N-CoR complex enables chromatin remodeler SNF2H to enhance repression by thyroid hormone receptor
    Theresa Alenghat
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6149, USA
    EMBO J 25:3966-74. 2006
  2. pmc Integrative genomic analysis of CREB defines a critical role for transcription factor networks in mediating the fed/fasted switch in liver
    Logan J Everett
    Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    BMC Genomics 14:337. 2013
  3. pmc A novel adipose-specific gene deletion model demonstrates potential pitfalls of existing methods
    Shannon E Mullican
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Endocrinol 27:127-34. 2013
  4. ncbi request reprint Developmental biology. How now, brown fat?
    Mitchell A Lazar
    Institute for Diabetes, Obesity, and Metabolism, Department of Medicine, University of Pennsylavania, 415 Curie Boulevard, Philadelphia, PA 19104, USA
    Science 321:1048-9. 2008
  5. pmc Thyroid hormone action: a binding contract
    Mitchell A Lazar
    University of Pennsylvania School of Medicine, 611 Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104 6149, USA
    J Clin Invest 112:497-9. 2003
  6. ncbi request reprint Resistin- and Obesity-associated metabolic diseases
    M A Lazar
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6149, USA
    Horm Metab Res 39:710-6. 2007
  7. ncbi request reprint How obesity causes diabetes: not a tall tale
    Mitchell A Lazar
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6149, USA
    Science 307:373-5. 2005
  8. ncbi request reprint Sweet dreams for LXR
    Mitchell A Lazar
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell Metab 5:159-61. 2007
  9. ncbi request reprint PPAR gamma, 10 years later
    Mitchell A Lazar
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6149, USA
    Biochimie 87:9-13. 2005
  10. ncbi request reprint DNA-independent and DNA-dependent mechanisms regulate the differential heterodimerization of the isoforms of the thyroid hormone receptor with retinoid X receptor
    M J Reginato
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 271:28199-205. 1996

Research Grants

  1. Univ of Pennsylvania Diabetes Endocrinology Res CTR
    MITCHELL LAZAR; Fiscal Year: 2006
  2. NUCLEAR HORMONE RECEPTORS IN ADIPOCYTE DIFFERENTIATION
    Mitchell A Lazar; Fiscal Year: 2010
  3. THYROID HORMONE RECEPTORS-REGULATION AND FUNCTION
    MITCHELL LAZAR; Fiscal Year: 2007
  4. Corepressors for the Orphan Receptor RevErb
    MITCHELL LAZAR; Fiscal Year: 2006
  5. NUCLEAR HORMONE RECEPTORS IN ADIPOCYTE DIFFERENTIATION
    MITCHELL LAZAR; Fiscal Year: 2003
  6. NUCLEAR HORMONE RECEPTORS IN ADIPOCYTE DIFFERENTIATION
    MITCHELL LAZAR; Fiscal Year: 2007
  7. Biology of the orphan receptor Rev-erbalpha
    MITCHELL LAZAR; Fiscal Year: 2007
  8. Biology of the orphan receptor Rev-erbalpha
    Mitchell A Lazar; Fiscal Year: 2010
  9. Univ of Pennsyvania Diabetes Endocrinology Res Ctr
    MITCHELL LAZAR; Fiscal Year: 2007
  10. BIOLOGY OF THE ORPHAN RECEPTOR REV/ERB
    MITCHELL LAZAR; Fiscal Year: 2001

Detail Information

Publications84

  1. pmc The N-CoR complex enables chromatin remodeler SNF2H to enhance repression by thyroid hormone receptor
    Theresa Alenghat
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6149, USA
    EMBO J 25:3966-74. 2006
    ..Thus, although not apparent from studies of transiently transfected reporter genes, gene repression by TR involves the targeting of chromatin remodeling factors to repressed genes by the HDAC activity of nuclear receptor corepressors...
  2. pmc Integrative genomic analysis of CREB defines a critical role for transcription factor networks in mediating the fed/fasted switch in liver
    Logan J Everett
    Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
    BMC Genomics 14:337. 2013
    ..The precise molecular mechanisms by which CREB specifically targets these genes in response to alternating hormonal cues remain to be elucidated...
  3. pmc A novel adipose-specific gene deletion model demonstrates potential pitfalls of existing methods
    Shannon E Mullican
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Endocrinol 27:127-34. 2013
    ....
  4. ncbi request reprint Developmental biology. How now, brown fat?
    Mitchell A Lazar
    Institute for Diabetes, Obesity, and Metabolism, Department of Medicine, University of Pennsylavania, 415 Curie Boulevard, Philadelphia, PA 19104, USA
    Science 321:1048-9. 2008
  5. pmc Thyroid hormone action: a binding contract
    Mitchell A Lazar
    University of Pennsylvania School of Medicine, 611 Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104 6149, USA
    J Clin Invest 112:497-9. 2003
    ....
  6. ncbi request reprint Resistin- and Obesity-associated metabolic diseases
    M A Lazar
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6149, USA
    Horm Metab Res 39:710-6. 2007
    ..Given the emerging interrelationship between inflammation and metabolic disease, hyperresistinemia may be a biomarker, and/or a mediator, of metabolic and inflammatory diseases in humans as well as in rodents...
  7. ncbi request reprint How obesity causes diabetes: not a tall tale
    Mitchell A Lazar
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6149, USA
    Science 307:373-5. 2005
    ....
  8. ncbi request reprint Sweet dreams for LXR
    Mitchell A Lazar
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell Metab 5:159-61. 2007
    ..However, the hydrophilic nature of glucose and its low affinity for LXR present a challenge to central dogma about the nature of the NR-ligand interaction...
  9. ncbi request reprint PPAR gamma, 10 years later
    Mitchell A Lazar
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6149, USA
    Biochimie 87:9-13. 2005
    ..Prospects for future research leading to new therapies for obesity and diabetes are also discussed...
  10. ncbi request reprint DNA-independent and DNA-dependent mechanisms regulate the differential heterodimerization of the isoforms of the thyroid hormone receptor with retinoid X receptor
    M J Reginato
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 271:28199-205. 1996
    ..Differential dependence upon DNA-binding for heterodimerization with RXR may influence transcriptional regulation by TRalpha isoforms...
  11. ncbi request reprint Progress in cardiovascular biology: PPAR for the course
    M A Lazar
    Division of Endocrinology, Diabetes and Metabolism, Departments of Medicine and Genetics and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nat Med 7:23-4. 2001
    ..These findings warrant an in-depth investigation into the gene regulatory mechanisms of PPAR ligands, which are currently being developed as drugs to treat atherosclerosis and diabetes...
  12. pmc East meets West: an herbal tea finds a receptor
    Mitchell A Lazar
    Departments of Medicine and Genetics, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6149, USA
    J Clin Invest 113:23-5. 2004
    ..This discovery could lead to improved pharmaceutical treatments for neonatal jaundice...
  13. ncbi request reprint Becoming fat
    Mitchell A Lazar
    Division of Endocrinology, Diabetes, and Metabolism, Departments of Medicine and Genetics, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 16:1-5. 2002
  14. ncbi request reprint Mechanisms regulating adipocyte expression of resistin
    Helen B Hartman
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and Genetics and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 277:19754-61. 2002
    ..TZD reduces resistin gene expression at least in part by reducing histone acetylation associated with the binding of C/EBPalpha in mature adipocytes...
  15. ncbi request reprint Genetic modulation of PPARgamma phosphorylation regulates insulin sensitivity
    Shamina M Rangwala
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Dev Cell 5:657-63. 2003
    ..Compounds that prevent PPARgamma phosphorylation or ligands that induce the conformation of nonphosphorylated PPARgamma may selectively enhance insulin sensitivity without increasing body weight...
  16. ncbi request reprint A futile metabolic cycle activated in adipocytes by antidiabetic agents
    Hong Ping Guan
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Nat Med 8:1122-8. 2002
    ..The 'futile' fuel cycle resulting from expression of GyK in adipocytes is thus a novel mechanism contributing to reduced FFA levels and perhaps insulin sensitization by antidiabetic therapies...
  17. ncbi request reprint Resistin: molecular history and prognosis
    Ronadip R Banerjee
    Division of Endocrinology, Diabetes, and Metabolism, Penn Diabetes Center, University of Pennsylvania School of Medicine, 415 Curie Blvd, Philadelphia, PA 19104 6149, USA
    J Mol Med (Berl) 81:218-26. 2003
    ..Here we consider a novel secreted factor first identified as a TZD-suppressible gene in mouse adipocytes, called resistin, and discuss what is currently known about resistin regulation and function in mouse and human...
  18. ncbi request reprint Differential gene regulation by PPARgamma agonist and constitutively active PPARgamma2
    Yong Li
    Division of Endocrinology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Mol Endocrinol 16:1040-8. 2002
    ..This conclusion has important implications for understanding biological effects of the TZDs on adipogenesis and insulin sensitization...
  19. ncbi request reprint The orphan nuclear receptor Rev-erbalpha recruits the N-CoR/histone deacetylase 3 corepressor to regulate the circadian Bmal1 gene
    Lei Yin
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia 19104 6149, USA
    Mol Endocrinol 19:1452-9. 2005
    ..These data demonstrate a new function for the N-CoR/HDAC3 complex in regulating the expression of genes involved in circadian rhythm by functioning as corepressor for Rev-erbalpha...
  20. ncbi request reprint Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathways
    Lei Yin
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 318:1786-9. 2007
    ..Thus, Rev-erbalpha serves as a heme sensor that coordinates the cellular clock, glucose homeostasis, and energy metabolism...
  21. pmc The histone-binding code of nuclear receptor co-repressors matches the substrate specificity of histone deacetylase 3
    Helen B Hartman
    Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, The Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, 611 CRB, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
    EMBO Rep 6:445-51. 2005
    ..The match between the specificity of acetyl-histone deacetylation by HDAC3 and the histone-binding preference of N-CoR/SMRT allows the co-repressor complex to stabilize and propagate repression of nuclear hormone receptor gene targets...
  22. pmc An inflammatory cascade leading to hyperresistinemia in humans
    Michael Lehrke
    Division of Endocrinology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    PLoS Med 1:e45. 2004
    ..Adipocyte-derived resistin is a circulating protein implicated in insulin resistance in rodents, but the role of human resistin is uncertain because it is produced largely by macrophages...
  23. ncbi request reprint The current biology of resistin
    Claire M Steppan
    Division of Endocrinology, Diabetes, and Metabolism, Departments of Medicine and Genetics, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    J Intern Med 255:439-47. 2004
    ..This review will summarize our current understanding of resistin and will attempt to provide a framework for future study of its role in rodent and human physiology...
  24. ncbi request reprint The corepressor silencing mediator for retinoid and thyroid hormone receptor facilitates cellular recovery from DNA double-strand breaks
    Jiujiu Yu
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6149, USA
    Cancer Res 66:9316-22. 2006
    ..Thus, the corepressor SMRT plays a novel and critical role in the cellular response to DSBs...
  25. pmc Re-expression of GATA2 cooperates with peroxisome proliferator-activated receptor-gamma depletion to revert the adipocyte phenotype
    Michael Schupp
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Univ of Pennsylvania School of Medicine, 700 CRB, 415 Curie Blvd, Philadelphia, PA 19104 6149, USA
    J Biol Chem 284:9458-64. 2009
    ..These results suggest that PPARgamma-independent down-regulation of GATA2 prevents reversion of mature adipocytes after PPARgamma depletion...
  26. pmc Adipocyte-specific expression of murine resistin is mediated by synergism between peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding proteins
    Takuya Tomaru
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6149, USA
    J Biol Chem 284:6116-25. 2009
    ....
  27. pmc Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex
    Matthew G Guenther
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    Genes Dev 16:3130-5. 2002
    ..The strict control of HDAC3 activity underscores the cellular imperative that histone deacetylation occur only in targeted regions of the genome...
  28. ncbi request reprint Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRalpha
    Michael Lehrke
    Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cell Metab 1:297-308. 2005
    ....
  29. ncbi request reprint The many faces of PPARgamma
    Michael Lehrke
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 123:993-9. 2005
    ....
  30. ncbi request reprint Mechanisms of obesity-associated insulin resistance: many choices on the menu
    Mohammed Qatanani
    Division of Endocrinology, Diabetes, and Metabolism, and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 21:1443-55. 2007
    ..Understanding the biology of these systems will inform the search for interventions that specifically prevent or treat insulin resistance and its associated pathologies...
  31. pmc Nuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiology
    Theresa Alenghat
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nature 456:997-1000. 2008
    ..These findings indicate that activation of Hdac3 by Ncor1 is a nodal point in the epigenetic regulation of circadian and metabolic physiology...
  32. ncbi request reprint Peroxisome proliferator-activated receptor gamma in diabetes and metabolism
    Shamina M Rangwala
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Trends Pharmacol Sci 25:331-6. 2004
    ..It might be possible to dissociate the anti-diabetic and adverse effects through selective modulation of PPAR-gamma activity...
  33. pmc PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1
    Patricia C Chui
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6149, USA
    J Clin Invest 115:2244-56. 2005
    ....
  34. pmc The N-CoR/histone deacetylase 3 complex is required for repression by thyroid hormone receptor
    Takahiro Ishizuka
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA
    Mol Cell Biol 23:5122-31. 2003
    ..Thus, HDAC3 is critical for repression by multiple nuclear receptors and the N-CoR HDAC3 complex plays a unique and necessary role in TR-mediated gene repression in human 293T cells...
  35. ncbi request reprint Resistin is an inflammatory marker of atherosclerosis in humans
    Muredach P Reilly
    Division of Cardiology, Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    Circulation 111:932-9. 2005
    ..Given the convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and atherosclerosis in humans...
  36. pmc Species-specific strategies underlying conserved functions of metabolic transcription factors
    Raymond E Soccio
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6149, USA
    Mol Endocrinol 25:694-706. 2011
    ..Analysis of factor binding in multiple species may be necessary to distinguish apparent species-unique noise and reveal functionally relevant information...
  37. pmc Cell-specific determinants of peroxisome proliferator-activated receptor gamma function in adipocytes and macrophages
    Martina I Lefterova
    University of Pennsylvania School of Medicine, 700 CRB, 415 Curie Blvd, Philadelphia, PA 19104 6149, USA
    Mol Cell Biol 30:2078-89. 2010
    ..Our data support the existence of an epigenomic hierarchy in which PPARgamma binding to cell-specific sites not marked by repressive marks opens chromatin and leads to local activation marks, including histone acetylation...
  38. ncbi request reprint Loss of resistin improves glucose homeostasis in leptin deficiency
    Yong Qi
    University of Pennsylvania School of Medicine, Division of Endocrinology, DiabetesMetabolism, 764 Clinical Research Building, 415 Curie Blvd, Philadelphia, PA 19104, USA
    Diabetes 55:3083-90. 2006
    ..Together, these results provide strong support for an important role of resistin in insulin resistance and diabetes associated with genetic or diet-induced obesity...
  39. doi request reprint Fingered for a fat fate
    Michael Schupp
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell Metab 11:244-5. 2010
    ..A recent report (Gupta et al., 2010) identifies the zinc finger protein Zfp423 as a determining factor in preadipocyte commitment...
  40. pmc Selective partial agonism of liver X receptor alpha is related to differential corepressor recruitment
    Caroline A Phelan
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Mol Endocrinol 22:2241-9. 2008
    ..Thus, differential recruitment of NCoR is a major determinant of partial agonism and selective LXR modulation of target genes...
  41. pmc Adipokines and the peripheral and neural control of energy balance
    Rexford S Ahima
    Department of Medicine, University of Pennsylvania School of Medicine, Division of Endocrinology, Diabetes and Metabolism, Philadelphia, Pennsylvania 19104, USA
    Mol Endocrinol 22:1023-31. 2008
    ..Understanding adipokine signaling in the brain and other organs will provide insights into the pathogenesis and treatment of obesity, diabetes and various metabolic disorders...
  42. pmc Gaining weight: the Keystone Symposium on PPAR and LXR
    Michael Lehrke
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 19:1737-42. 2005
    ..In recognition of this, a recent Keystone Symposium was devoted to these metabolic receptors. Here, we summarize some of the major highlights and future projections discussed at the meeting...
  43. ncbi request reprint The nuclear receptor corepressor deacetylase activating domain is essential for repression by thyroid hormone receptor
    Takahiro Ishizuka
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia 19104 6149, USA
    Mol Endocrinol 19:1443-51. 2005
    ..Introduction of a single amino acid mutation in the DAD similarly disabled the corepressor function of N-CoR. Thus, the DAD domain of N-CoR is singularly essential for repression by TR...
  44. pmc Corepressors selectively control the transcriptional activity of PPARgamma in adipocytes
    Hong Ping Guan
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 19:453-61. 2005
    ..Thus, selective modulation of adipocyte PPARgamma target genes by TZDs involves the dissociation of corepressors by direct and indirect mechanisms...
  45. pmc Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response
    Gary D Kao
    Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Cell Biol 160:1017-27. 2003
    ..Our combined results suggest that HDAC4 is a critical component of the DNA damage response pathway that acts through 53BP1 and perhaps contributes in maintaining the G2 cell cycle checkpoint...
  46. ncbi request reprint The dawn of the SPPARMs?
    Shamina M Rangwala
    Division of Endocrinology, Department of Medicine, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Sci STKE 2002:pe9. 2002
    ..A newly described PPARgamma ligand may represent an initial step in this direction and could lead to improved agents for treating insulin resistance in type II diabetes...
  47. ncbi request reprint ETO interacting proteins
    Bruce A Hug
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Oncogene 23:4270-4. 2004
    ..These investigations have provided mechanistic insight into corepressor recruitment by ETO and clues to the leukemogenic activity of AML1-ETO...
  48. ncbi request reprint Cooperative function of Aml1-ETO corepressor recruitment domains in the expansion of primary bone marrow cells
    Bruce A Hug
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA
    Cancer Res 62:2906-12. 2002
    ..These findings suggest that the NH2 and NH4 domains function cooperatively in the corepressor environment of primary bone marrow cells...
  49. ncbi request reprint Resistin and obesity-associated insulin resistance
    Claire M Steppan
    Division of Endocrinology, Diabetes, and Metabolism, Depts of Medicine and Genetics and The Penn Diabetes Center, University of Pennsylvania Medical Center, Philadelphia, PA 19104 6149, USA
    Trends Endocrinol Metab 13:18-23. 2002
    ..Thus, resistin is a potential link between TZDs, obesity and insulin resistance in the mouse. Future studies must address the mechanism of action and biological role of resistin and related family members in mice and humans...
  50. ncbi request reprint Regulation of fasted blood glucose by resistin
    Ronadip R Banerjee
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Penn Diabetes Center, 611 CRB, 415 Curie Boulevard, Universityof Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 303:1195-8. 2004
    ..Remarkably, lack of resistin diminishes the increase in post-fast blood glucose normally associated with increased weight, suggesting a role for resistin in mediating hyperglycemia associated with obesity...
  51. pmc Bifunctional role of Rev-erbalpha in adipocyte differentiation
    Jing Wang
    University of Pennsylvania School of Medicine, 700 CRB, 415 Curie Blvd, Philadelphia, PA 19104 6149, USA
    Mol Cell Biol 28:2213-20. 2008
    ..Thus, opposite to what might be predicted from Rev-erbalpha gene expression, Rev-erbalpha protein levels must rise and then fall for adipocyte differentiation to occur...
  52. ncbi request reprint A widely used retinoic acid receptor antagonist induces peroxisome proliferator-activated receptor-gamma activity
    Michael Schupp
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6149, USA
    Mol Pharmacol 71:1251-7. 2007
    ..Ro 41-5253 is a PPARgamma agonist as well as an RARalpha antagonist whose pleiotropic effects on NRs may signify a unique spectrum of biological responses...
  53. pmc PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale
    Martina I Lefterova
    Institute for Diabetes, Obesity, and Metabolism, and Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 22:2941-52. 2008
    ..Thus, PPARgamma and C/EBP factors cooperatively orchestrate adipocyte biology by adjacent binding on an unanticipated scale...
  54. pmc Absence of bacterially induced RELMbeta reduces injury in the dextran sodium sulfate model of colitis
    Laila D McVay
    Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 116:2914-23. 2006
    ....
  55. ncbi request reprint Thiazolidinedione activation of peroxisome proliferator-activated receptor gamma can enhance mitochondrial potential and promote cell survival
    Y Lynn Wang
    Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6160, USA
    J Biol Chem 277:31781-8. 2002
    ..These data indicate that activation of PPAR gamma with TZDs can promote cell survival and suggest that PPAR gamma activation may potentially augment the immune responses of diabetic patients...
  56. pmc Endoplasmic reticulum stress regulates adipocyte resistin expression
    Martina I Lefterova
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    Diabetes 58:1879-86. 2009
    ..We investigated whether endoplasmic reticulum (ER) stress, which is characteristic of obese adipose tissue, regulates resistin expression in cultured mouse adipocytes...
  57. pmc Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbalpha
    Nan Wu
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 23:2201-9. 2009
    ..Thus, Rev-erbalpha modulates the synthesis of its own ligand in a negative feedback pathway that maintains heme levels and regulates cellular energy metabolism...
  58. pmc A SANT motif in the SMRT corepressor interprets the histone code and promotes histone deacetylation
    Jiujiu Yu
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6149, USA
    EMBO J 22:3403-10. 2003
    ..This implies that the SMRT HID participates in interpreting the histone code in a feed-forward mechanism that promotes and maintains histone deacetylation at genomic sites of SMRT recruitment...
  59. pmc Structure of Rev-erbalpha bound to N-CoR reveals a unique mechanism of nuclear receptor-co-repressor interaction
    Caroline A Phelan
    Division of Endocrinology, Diabetes and Metabolism, Departments of Medicine and Genetics, The Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Nat Struct Mol Biol 17:808-14. 2010
    ..The previously uncharacterized secondary structure induced by ID1 peptide binding advances our understanding of nuclear receptor-co-repressor interactions...
  60. pmc DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells
    David J Steger
    Division of Hematology, Abramson Research Center 315A, The Children s Hospital of Philadelphia, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA
    Mol Cell Biol 28:2825-39. 2008
    ....
  61. doi request reprint New developments in adipogenesis
    Martina I Lefterova
    Division of Endocrinology, Diabetes and Metabolism, Department of Medicine and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Trends Endocrinol Metab 20:107-14. 2009
    ..Improved understanding of brown and white adipocyte origins and the integrative biology of adipogenesis might lead to more effective strategies for the treatment of obesity and metabolic disease...
  62. pmc Retinol saturase promotes adipogenesis and is downregulated in obesity
    Michael Schupp
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 106:1105-10. 2009
    ..Thus, RetSat plays an important role in the biology of adipocytes, where it favors normal differentiation, yet is reduced in the obese state. RetSat is thus a novel target for therapeutic intervention in metabolic disease...
  63. pmc A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activity
    Yun Li
    Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
    Genes Dev 20:2566-79. 2006
    ....
  64. ncbi request reprint Mouse and human resistins impair glucose transport in primary mouse cardiomyocytes, and oligomerization is required for this biological action
    Christophe Graveleau
    Division of Endocrinology, Metabolism, and Diabetes, University of Utah, Salt Lake City, Utah 84112, USA
    J Biol Chem 280:31679-85. 2005
    ..Thus, in cardiomyocytes, both mouse and human resistins directly impair glucose transport; and in contrast to effects on the liver, these actions of resistin require oligomerization...
  65. ncbi request reprint CXCL16 is a marker of inflammation, atherosclerosis, and acute coronary syndromes in humans
    Michael Lehrke
    Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    J Am Coll Cardiol 49:442-9. 2007
    ..This study was designed to determine the association of CXCL16 with inflammation, atherosclerosis, and acute coronary syndromes...
  66. ncbi request reprint The orphan nuclear receptor Rev-erb alpha regulates circadian expression of plasminogen activator inhibitor type 1
    Jing Wang
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    J Biol Chem 281:33842-8. 2006
    ..Thus, our results suggest that Rev-erb alpha is a major determinant of the circadian PAI-1 expression and a potential modulator of the morning susceptibility to myocardial infarction...
  67. ncbi request reprint Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock
    Lei Yin
    Division of Endocrinology, Diabetes, and Metabolism, and University of Pennsylvania School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA
    Science 311:1002-5. 2006
    ..Control of Rev-erbalpha protein stability is thus a critical component of the peripheral clock and a biological target of lithium therapy...
  68. ncbi request reprint HIV protease inhibitor-specific alterations in human adipocyte differentiation and metabolism
    Roy J Kim
    Division of Endocrinology, Children s Hospital of Philadelphia, Pennsylvania, USA
    Obesity (Silver Spring) 14:994-1002. 2006
    ..We hypothesized that the less deleterious clinical effects of atazanavir would be reflected in physiological differences observed in PI-treated adipocytes...
  69. pmc Inflammatory induction of human resistin causes insulin resistance in endotoxemic mice
    Hyeong Kyu Park
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    Diabetes 60:775-83. 2011
    ..Given the mounting evidence that obesity and type 2 diabetes are inflammatory diseases, we sought to determine the relationship between inflammatory increases in human resistin and insulin resistance...
  70. ncbi request reprint Nutritional supplementation with trans-10, cis-12-conjugated linoleic acid induces inflammation of white adipose tissue
    Hélène Poirier
    Physiologie de la Nutrition, ENSBANA, Unité Mixte de Recherche 5170 CESG Centre National de la Recherche Scientifique Institut National de la Recherche Agronomique Université de Bourgogne, Dijon, 21000 France
    Diabetes 55:1634-41. 2006
    ..Thus, CLA supplementation directly induces inflammatory gene expression in adipocytes and also promotes macrophage infiltration into adipose tissue to a local inflammatory state that contributes to insulin resistance...
  71. ncbi request reprint Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR
    Wolfgang Fischle
    Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA 94141, USA
    Mol Cell 9:45-57. 2002
    ..These observations indicate that class II HDACs regulate transcription by bridging the enzymatically active SMRT/N-CoR-HDAC3 complex and select transcription factors independently of any intrinsic HDAC activity...
  72. ncbi request reprint The humoral side of insulin resistance
    Mitchell A Lazar
    Nat Med 12:43-4. 2006
  73. ncbi request reprint Inflamed about obesity
    Michael Lehrke
    Nat Med 10:126-7. 2004
  74. ncbi request reprint Identification and characterization of a selective peroxisome proliferator-activated receptor beta/delta (NR1C2) antagonist
    Barry G Shearer
    Research and Development, GlaxoSmithKline, Research Triangle Park, NC 27709, USA
    Mol Endocrinol 22:523-9. 2008
    ..Here we describe the first report of a PPARbeta/delta small molecule antagonist ligand. This antagonist ligand will be a useful tool for elucidating the biological roles of PPARbeta/delta...
  75. pmc Coactivators and corepressors of NF-kappaB in IkappaB alpha gene promoter
    Zhanguo Gao
    Pennington Biomedical Research Center, Louisiana State University Systems, Baton Rouge, Louisiana 70808, USA
    J Biol Chem 280:21091-8. 2005
    ..This model may represent a mechanism for integration of extracellular signals into a precise control of gene transcription...
  76. pmc Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone
    Leanne Wilson-Fritch
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, 01601, USA
    J Clin Invest 114:1281-9. 2004
    ....
  77. pmc PPARgamma regulates adipose triglyceride lipase in adipocytes in vitro and in vivo
    Erin E Kershaw
    Div of Endocrinology and Metabolism, Dept of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA
    Am J Physiol Endocrinol Metab 293:E1736-45. 2007
    ..Thus, PPARgamma positively regulates ATGL mRNA and protein expression in mature adipocytes in vitro and in adipose tissue in vivo, suggesting a role for ATGL in mediating PPARgamma's effects on lipid metabolism...
  78. pmc Activation of SOCS-3 by resistin
    Claire M Steppan
    Pfizer Inc, PRGD, MS220 3145, Eastern Point Rd, Groton, CT 06340, USA
    Mol Cell Biol 25:1569-75. 2005
    ..SOCS-3 induction is the first cellular effect of resistin that is independent of insulin and is a likely mediator of resistin's inhibitory effect on insulin signaling in adipocytes...
  79. pmc Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex
    Shingo Kajimura
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 22:1397-409. 2008
    ..These data show that the regulated docking of the CtBP proteins on PRDM16 controls the brown and white fat-selective gene programs...
  80. ncbi request reprint The coiled-coil domain is the structural determinant for mammalian homologues of Drosophila Sina-mediated degradation of promyelocytic leukemia protein and other tripartite motif proteins by the proteasome
    Mirco Fanelli
    Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy
    J Biol Chem 279:5374-9. 2004
    ..These results identify PML and other TRIMs as new factors post-translationally regulated by SIAH and involve the coiled-coil region of PML and of other SIAH substrates as a novel structural determinant for targeted degradation...
  81. ncbi request reprint Biochemical isolation and analysis of a nuclear receptor corepressor complex
    Matthew G Guenther
    Methods Enzymol 364:246-57. 2003
  82. ncbi request reprint International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors
    Liliane Michalik
    Center for Integrative Genomics, National Research Centre Frontiers in Genetics, University of Lausanne, Lausanne, Switzerland
    Pharmacol Rev 58:726-41. 2006
    ..Thus, selective action of PPARs in vivo results from the interplay at a given time point between expression levels of each of the three PPAR and RXR isotypes, affinity for a specific promoter PPRE, and ligand and cofactor availabilities...
  83. pmc Structural insights into the interaction and activation of histone deacetylase 3 by nuclear receptor corepressors
    Anna Codina
    Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    Proc Natl Acad Sci U S A 102:6009-14. 2005
    ..Importantly, one surface-exposed lysine is required for activation of HDAC3, but not for interaction. This lysine may play a uniquely important role in the mechanism of activating HDAC3...
  84. doi request reprint Dok1 mediates high-fat diet-induced adipocyte hypertrophy and obesity through modulation of PPAR-gamma phosphorylation
    Tetsuya Hosooka
    Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7 5 1 Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
    Nat Med 14:188-93. 2008
    ..These results indicate that Dok1 promotes adipocyte hypertrophy by counteracting the inhibitory effect of ERK on PPAR-gamma and may thus confer predisposition to diet-induced obesity...

Research Grants45

  1. Univ of Pennsylvania Diabetes Endocrinology Res CTR
    MITCHELL LAZAR; Fiscal Year: 2006
    ..Moreover, the present Center grant (NIDDK19525) remains the foundation of inter-disciplinary diabetes research in Philadelphia...
  2. NUCLEAR HORMONE RECEPTORS IN ADIPOCYTE DIFFERENTIATION
    Mitchell A Lazar; Fiscal Year: 2010
    ..Thus, the insights gained from this work are likely to lead to new and deeper insights that may be translated into novel treatment strategies for metabolic disorders, including obesity, diabetes, and cardiovascular disease. ..
  3. THYROID HORMONE RECEPTORS-REGULATION AND FUNCTION
    MITCHELL LAZAR; Fiscal Year: 2007
    ..Such proteins will be cloned and characterized using dihybrid screens in yeast. These studies will provide insight into hormone action in general, and enhance understanding of many pathophysiological states. ..
  4. Corepressors for the Orphan Receptor RevErb
    MITCHELL LAZAR; Fiscal Year: 2006
    ..abstract_text> ..
  5. NUCLEAR HORMONE RECEPTORS IN ADIPOCYTE DIFFERENTIATION
    MITCHELL LAZAR; Fiscal Year: 2003
    ..abstract_text> ..
  6. NUCLEAR HORMONE RECEPTORS IN ADIPOCYTE DIFFERENTIATION
    MITCHELL LAZAR; Fiscal Year: 2007
    ..abstract_text> ..
  7. Biology of the orphan receptor Rev-erbalpha
    MITCHELL LAZAR; Fiscal Year: 2007
    ..This has the potential to lead to new understanding of circadian and metabolic disorders, including obesity, diabetes, and cardiovascular disease. ..
  8. Biology of the orphan receptor Rev-erbalpha
    Mitchell A Lazar; Fiscal Year: 2010
    ..This has the potential to lead to new understanding of circadian and metabolic disorders, including obesity, diabetes, and cardiovascular disease. ..
  9. Univ of Pennsyvania Diabetes Endocrinology Res Ctr
    MITCHELL LAZAR; Fiscal Year: 2007
    ..These functions of the Penn DERC maintain the diabetes-related research program at this Center at the forefront of biomedical science. ..
  10. BIOLOGY OF THE ORPHAN RECEPTOR REV/ERB
    MITCHELL LAZAR; Fiscal Year: 2001
    ..These studies are required to understand the function of Rev-Erb and ROR-alpha and, more generally, will define novel mechanisms underlying specificity of gene regulation by the nuclear hormone receptor superfamily. ..
  11. BIOLOGY OF THE ORPHAN RECEPTOR REV-ERBRA ALPHA
    MITCHELL LAZAR; Fiscal Year: 1993
    ..These studies will also provide insight into the biological significance of orphan receptors as well as the mechanisms of action of nuclear hormone receptor family members...