Research Topics
| MITCHELL LAZARSummaryAffiliation: University of Pennsylvania Country: USA Publications
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Publications
The N-CoR complex enables chromatin remodeler SNF2H to enhance repression by thyroid hormone receptorTheresa 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...- A novel adipose-specific gene deletion model demonstrates potential pitfalls of existing methodsShannon 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.... 
DNA-independent and DNA-dependent mechanisms regulate the differential heterodimerization of the isoforms of the thyroid hormone receptor with retinoid X receptorM 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...- How obesity causes diabetes: not a tall taleMitchell 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.... - PPAR gamma, 10 years laterMitchell 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... - Thyroid hormone action: a binding contractMitchell 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.... - Sweet dreams for LXRMitchell 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... - East meets West: an herbal tea finds a receptorMitchell 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... - Resistin- and Obesity-associated metabolic diseasesM 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... - 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 - Progress in cardiovascular biology: PPAR for the courseM 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... - Becoming fatMitchell 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 - Mechanisms regulating adipocyte expression of resistinHelen 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... - The orphan nuclear receptor Rev-erbalpha recruits the N-CoR/histone deacetylase 3 corepressor to regulate the circadian Bmal1 geneLei 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... - Genetic modulation of PPARgamma phosphorylation regulates insulin sensitivityShamina 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... - A futile metabolic cycle activated in adipocytes by antidiabetic agentsHong-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... - Resistin: molecular history and prognosisRonadip 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... - Differential gene regulation by PPARgamma agonist and constitutively active PPARgamma2Yong 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... - Rev-erbalpha, a heme sensor that coordinates metabolic and circadian pathwaysLei 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... - Adipocyte-specific expression of murine resistin is mediated by synergism between peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding proteinsTakuya 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.... - The histone-binding code of nuclear receptor co-repressors matches the substrate specificity of histone deacetylase 3Helen 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... - Re-expression of GATA2 cooperates with peroxisome proliferator-activated receptor-gamma depletion to revert the adipocyte phenotypeMichael 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... - The corepressor silencing mediator for retinoid and thyroid hormone receptor facilitates cellular recovery from DNA double-strand breaksJiujiu 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... 
An inflammatory cascade leading to hyperresistinemia in humansMichael Lehrke
Division of Endocrinology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
PLoS Med 1:e45. 2004..CONCLUSIONS: Inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states...- The current biology of resistinClaire 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... - Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complexMatthew 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... - PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1Patricia 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.... - Peroxisome proliferator-activated receptor gamma in diabetes and metabolismShamina 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... - The N-CoR/histone deacetylase 3 complex is required for repression by thyroid hormone receptorTakahiro 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... - Mechanisms of obesity-associated insulin resistance: many choices on the menuMohammed 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... - Nuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiologyTheresa 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... - Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRalphaMichael Lehrke
Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Cell Metab 1:297-308. 2005.... - The many faces of PPARgammaMichael 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.... - Selective partial agonism of liver X receptor alpha is related to differential corepressor recruitmentCaroline 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... - 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... - Cooperative function of Aml1-ETO corepressor recruitment domains in the expansion of primary bone marrow cellsBruce 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... - Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage responseGary 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... - ETO interacting proteinsBruce 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... - Adipokines and the peripheral and neural control of energy balanceRexford 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... - Loss of resistin improves glucose homeostasis in leptin deficiencyYong 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... - Corepressors selectively control the transcriptional activity of PPARgamma in adipocytesHong 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... 
Fingered for a fat fateMichael 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...- Species-specific strategies underlying conserved functions of metabolic transcription factorsRaymond 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... - The nuclear receptor corepressor deacetylase activating domain is essential for repression by thyroid hormone receptorTakahiro 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... - Resistin is an inflammatory marker of atherosclerosis in humansMuredach 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... - Gaining weight: the Keystone Symposium on PPAR and LXRMichael 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... - Resistin and obesity-associated insulin resistanceClaire 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... - Cell-specific determinants of peroxisome proliferator-activated receptor gamma function in adipocytes and macrophagesMartina 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... - A widely used retinoic acid receptor antagonist induces peroxisome proliferator-activated receptor-gamma activityMichael 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... - Thiazolidinedione activation of peroxisome proliferator-activated receptor gamma can enhance mitochondrial potential and promote cell survivalY 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... - Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbalphaNan 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... - Bifunctional role of Rev-erbalpha in adipocyte differentiationJing 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... - PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scaleMartina 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... - Endoplasmic reticulum stress regulates adipocyte resistin expressionMartina 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... - Absence of bacterially induced RELMbeta reduces injury in the dextran sodium sulfate model of colitisLaila D McVay
Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Clin Invest 116:2914-23. 2006.... - Regulation of fasted blood glucose by resistinRonadip 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... - CXCL16 is a marker of inflammation, atherosclerosis, and acute coronary syndromes in humansMichael 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... - Structure of Rev-erbalpha bound to N-CoR reveals a unique mechanism of nuclear receptor-co-repressor interactionCaroline 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... - New developments in adipogenesisMartina 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... - Retinol saturase promotes adipogenesis and is downregulated in obesityMichael 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... - Mouse and human resistins impair glucose transport in primary mouse cardiomyocytes, and oligomerization is required for this biological actionChristophe 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... - A SANT motif in the SMRT corepressor interprets the histone code and promotes histone deacetylationJiujiu 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... - DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cellsDavid 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.... - The orphan nuclear receptor Rev-erb alpha regulates circadian expression of plasminogen activator inhibitor type 1Jing 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... - Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clockLei 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... - A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activityYun 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.... - HIV protease inhibitor-specific alterations in human adipocyte differentiation and metabolismRoy J Kim
Division of Endocrinology, Children's Hospital of Philadelphia, Pennsylvania, USA
Obesity (Silver Spring) 14:994-1002. 2006..DISCUSSION: These data suggest that the distinct metabolic side effect profiles of these PIs could be a consequence of their differential effects on adipocyte physiology... - Inflammatory induction of human resistin causes insulin resistance in endotoxemic miceHyeong 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... - Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazoneLeanne Wilson-Fritch
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, 01601, USA
J Clin Invest 114:1281-9. 2004.... - Inflamed about obesityMichael Lehrke
Nat Med 10:126-7. 2004 - Activation of SOCS-3 by resistinClaire 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... - International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptorsLiliane 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... - PPARgamma regulates adipose triglyceride lipase in adipocytes in vitro and in vivoErin 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... - Dok1 mediates high-fat diet-induced adipocyte hypertrophy and obesity through modulation of PPAR-gamma phosphorylationTetsuya 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... - 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 proteasomeMirco 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... - Biochemical isolation and analysis of a nuclear receptor corepressor complexMatthew G Guenther
Methods Enzymol 364:246-57. 2003 - Coactivators and corepressors of NF-kappaB in IkappaB alpha gene promoterZhanguo 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... - Structural insights into the interaction and activation of histone deacetylase 3 by nuclear receptor corepressorsAnna 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... - Identification and characterization of a selective peroxisome proliferator-activated receptor beta/delta (NR1C2) antagonistBarry 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... - Nutritional supplementation with trans-10, cis-12-conjugated linoleic acid induces inflammation of white adipose tissueHélène 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... - Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complexShingo 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... - The humoral side of insulin resistanceMitchell A Lazar
Nat Med 12:43-4. 2006 - Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoRWolfgang 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...
Research Grants
- Univ of Pennsylvania Diabetes Endocrinology Res CTRMITCHELL LAZAR; Fiscal Year: 2006..Moreover, the present Center grant (NIDDK19525) remains the foundation of inter-disciplinary diabetes research in Philadelphia...
- NUCLEAR HORMONE RECEPTORS IN ADIPOCYTE DIFFERENTIATIONMitchell 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. ..
- THYROID HORMONE RECEPTORS-REGULATION AND FUNCTIONMITCHELL 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. ..
- Corepressors for the Orphan Receptor RevErbMITCHELL LAZAR; Fiscal Year: 2006..abstract_text> ..
- NUCLEAR HORMONE RECEPTORS IN ADIPOCYTE DIFFERENTIATIONMITCHELL LAZAR; Fiscal Year: 2003..abstract_text> ..
- NUCLEAR HORMONE RECEPTORS IN ADIPOCYTE DIFFERENTIATIONMITCHELL LAZAR; Fiscal Year: 2007..abstract_text> ..
- Biology of the orphan receptor Rev-erbalphaMITCHELL LAZAR; Fiscal Year: 2007..This has the potential to lead to new understanding of circadian and metabolic disorders, including obesity, diabetes, and cardiovascular disease. ..
- Biology of the orphan receptor Rev-erbalphaMitchell 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. ..
- Univ of Pennsyvania Diabetes Endocrinology Res CtrMITCHELL 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. ..
- BIOLOGY OF THE ORPHAN RECEPTOR REV/ERBMITCHELL 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. ..
- BIOLOGY OF THE ORPHAN RECEPTOR REV-ERBRA ALPHAMITCHELL 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...