Photo of Bruce M. Spiegelman,  PhD

Bruce M. Spiegelman, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3567
Fax: (617) 632-5363


bruce_spiegelman@dfci.harvard.edu

Bruce M. Spiegelman, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Stanley J. Korsmeyer Professor of Cell Biology and Medicine, Cell Biology, Harvard Medical School
  • Stanley J. Korsmeyer Professor of Cell Biology and Medicine, Medicine, Harvard Medical School
  • Professor, Cancer Biology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

We are interested in the regulation of cell differentiation and pathways of differentiation that can be used to force the maturation of human tumors. We have described the fucntion of a novel nuclear receptor, PPARgamma, that controls the differentiation of adipose cells. This transcription factor is also the functioning receptor of the thiazolidinedione (TZD) class of anti-diabetes drugs. Ligand activation of PPARgamma also derived from breast, prostate and colon. Our research is focused on pathways of differentiation induced by activation of PPARgamma in normal and malignant cells. In addition, we are interested in mutations acquired in the PPARgamma pathways during tumorigenesis.

Publications

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  • Banks AS, McAllister FE, Camporez JP, Zushin PJ, Jurczak MJ, Laznik-Bogoslavski D, Shulman GI, Gygi SP, Spiegelman BM. An ERK/Cdk5 axis controls the diabetogenic actions of PPAR粒. Nature 2015; 517:391-5. PubMed
  • Kir S, White JP, Kleiner S, Kazak L, Cohen P, Baracos VE, Spiegelman BM. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature 2014; 513:100-4. PubMed
  • Rao RR, Long JZ, White JP, Svensson KJ, Lou J, Lokurkar I, Jedrychowski MP, Ruas JL, Wrann CD, Lo JC, Camera DM, Lachey J, Gygi S, Seehra J, Hawley JA, Spiegelman BM. Meteorin-like Is a Hormone that Regulates Immune-Adipose Interactions to Increase Beige Fat Thermogenesis. Cell 2014; 157:1279-91. PubMed
  • Long JZ, Svensson KJ, Tsai L, Zeng X, Roh HC, Kong X, Rao RR, Lou J, Lokurkar I, Baur W, Castellot JJ, Rosen ED, Spiegelman BM. A Smooth Muscle-Like Origin for Beige Adipocytes. Cell Metab 2014. PubMed
  • Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, Lo JC, Zeng X, Ye L, Khandekar MJ, Wu J, Gunawardana SC, Banks AS, Camporez JP, Jurczak MJ, Kajimura S, Piston DW, Mathis D, Cinti S, Shulman GI, Seale P, Spiegelman BM. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 2014; 156:304-16. PubMed
  • Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, Lin JD, Greenberg ME, Spiegelman BM. Exercise induces hippocampal BDNF through a PGC-1留/FNDC5 pathway. Cell Metab 2013; 18:649-59. PubMed
  • Ye L, Wu J, Cohen P, Kazak L, Khandekar MJ, Jedrychowski MP, Zeng X, Gygi SP, Spiegelman BM. Fat cells directly sense temperature to activate thermogenesis. Proc Natl Acad Sci U S A 2013; 110:12480-5. PubMed
  • Vazquez F, Lim JH, Chim H, Bhalla K, Girnun G, Pierce K, Clish CB, Granter SR, Widlund HR, Spiegelman BM, Puigserver P. PGC1留 expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress. Cancer Cell 2013; 23:287-301. PubMed
  • Ye L, Kleiner S, Wu J, Sah R, Gupta RK, Banks AS, Cohen P, Khandekar MJ, Boström P, Mepani RJ, Laznik D, Kamenecka TM, Song X, Liedtke W, Mootha VK, Puigserver P, Griffin PR, Clapham DE, Spiegelman BM. TRPV4 Is a Regulator of Adipose Oxidative Metabolism, Inflammation, and Energy Homeostasis. Cell 2012; 151:96-110. PubMed
  • Handschin C, Spiegelman BM. PGC-1 Coactivators and the Regulation of Skeletal Muscle Fiber-Type Determination. Cell Metab 2011; 13:351. PubMed
  • Chakkalakal JV, Nishimune H, Ruas JL, Spiegelman BM, Sanes JR. Retrograde influence of muscle fibers on their innervation revealed by a novel marker for slow motoneurons. Development 2010; 137:3489-99. PubMed
  • Choi JH, Banks AS, Estall JL, Kajimura S, Boström P, Laznik D, Ruas JL, Chalmers MJ, Kamenecka TM, Blüher M, Griffin PR, Spiegelman BM. Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5. Nature 2010; 466:451-6. PubMed
  • Volakakis N, Kadkhodaei B, Joodmardi E, Wallis K, Panman L, Silvaggi J, Spiegelman BM, Perlmann T. NR4A orphan nuclear receptors as mediators of CREB-dependent neuroprotection. Proc Natl Acad Sci U S A 2010; 107:12317-22. PubMed
  • Kajimura S, Seale P, Spiegelman BM. Transcriptional control of brown fat development. Cell Metab 2010; 11:257-62. PubMed
  • Gupta RK, Arany Z, Seale P, Mepani RJ, Ye L, Conroe HM, Roby YA, Kulaga H, Reed RR, Spiegelman BM. Transcriptional control of preadipocyte determination by Zfp423. Nature 2010; 464:619-23. PubMed
  • Handschin C, Summermatter S, LeBrasseur NK, Lin J, Spiegelman BM. For a pragmatic approach to exercise studies. J Appl Physiol 2010; 108:223-3; author reply 226. PubMed
  • Estall JL, Ruas JL, Choi CS, Laznik D, Badman M, Maratos-Flier E, Shulman GI, Spiegelman BM. PGC-1alpha negatively regulates hepatic FGF21 expression by modulating the heme/Rev-Erb(alpha) axis. Proc Natl Acad Sci U S A 2010; 106:22510-5. PubMed
  • Wenz T, Rossi SG, Rotundo RL, Spiegelman BM, Moraes CT. Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci U S A 2009; 106:20405-10. PubMed
  • Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, Spiegelman BM. Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex. Nature 2009; 460:1154-8. PubMed
  • Kleiner S,Nguyen-Tran V,Bare O,Huang X,Spiegelman BM,Wu Z. PPARdelta agonism activates fatty acid oxidation via PGC-1alpha but does not increase mitochondrial gene expression and function. J Biol Chem 2009; 284:18624-33. PubMed
  • Estall JL,Kahn M,Cooper MP,Fisher FM,Wu MK,Laznik D,Qu L,Cohen DE,Shulman GI,Spiegelman BM. Sensitivity of lipid metabolism and insulin signaling to genetic alterations in hepatic PGC-1{alpha} expression. Diabetes 2009; 58:1499-508. PubMed
  • Seale P,Kajimura S,Spiegelman BM. Transcriptional control of brown adipocyte development and physiological function--of mice and men. Genes Dev 2009; 23:788-97. PubMed
  • Choi CS,Befroy DE,Codella R,Kim S,Reznick RM,Hwang YJ,Liu ZX,Lee HY,Distefano A,Samuel VT,Zhang D,Cline GW,Handschin C,Lin J,Petersen KF,Spiegelman BM,Shulman GI. Paradoxical effects of increased expression of PGC-1alpha on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism. Proc Natl Acad Sci U S A 2008; 105:19926-31. PubMed
  • Cooper MP,Uldry M,Kajimura S,Arany Z,Spiegelman BM. Modulation of PGC-1 coactivator pathways in brown fat differentiation through LRP130. J Biol Chem 2008; 283:31960-7. PubMed
  • Girnun GD,Chen L,Silvaggi J,Drapkin R,Chirieac LR,Padera RF,Upadhyay R,Vafai SB,Weissleder R,Mahmood U,Naseri E,Buckley S,Li D,Force J,McNamara K,Demetri G,Spiegelman BM,Wong KK. Regression of drug-resistant lung cancer by the combination of rosiglitazone and carboplatin. Clin Cancer Res 2008; 14:6478-86. PubMed
  • Walkey CJ,Spiegelman BM. A functional peroxisome proliferator-activated receptor-gamma ligand-binding domain is not required for adipogenesis. J Biol Chem 2008; 283:24290-4. PubMed
  • Wenz T,Diaz F,Spiegelman BM,Moraes CT. Activation of the PPAR/PGC-1alpha pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype. Cell Metab 2008; 8:249-56. PubMed
  • Seale P,Bjork B,Yang W,Kajimura S,Chin S,Kuang S,Scime A,Devarakonda S,Conroe HM,Erdjument-Bromage H,Tempst P,Rudnicki MA,Beier DR,Spiegelman BM. PRDM16 controls a brown fat/skeletal muscle switch. Nature 2008; 454:961-7. PubMed
  • Handschin C,Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature 2008; 454:463-9. PubMed
  • Kajimura S,Seale P,Tomaru T,Erdjument-Bromage H,Cooper MP,Ruas JL,Chin S,Tempst P,Lazar MA,Spiegelman BM. Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes Dev 2008; 22:1397-409. PubMed
  • Calvo JA, Daniels TG, Wang X, Paul A, Lin J, Spiegelman BM, Stevenson SC, Rangwala SM. Muscle-specific expression of PPAR{gamma} coactivator-1{alpha} improves exercise performance and increases peak oxygen uptake. J Appl Physiol 2008; 104:1304-12. PubMed
  • Arany Z, Wagner BK, Ma Y, Chinsomboon J, Laznik D, Spiegelman BM. Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1alpha and oxidative phosphorylation. Proc Natl Acad Sci U S A 2008; 105:4721-6. PubMed
  • Arany Z, Foo SY, Ma Y, Ruas JL, Bommi-Reddy A, Girnun G, Cooper M, Laznik D, Chinsomboon J, Rangwala SM, Baek KH, Rosenzweig A, Spiegelman BM. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 2008; 451:1008-12. PubMed
  • Handschin C, Choi CS, Chin S, Kim S, Kawamori D, Kurpad AJ, Neubauer N, Hu J, Mootha VK, Kim YB, Kulkarni RN, Shulman GI, Spiegelman BM. Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk. J Clin Invest 2007; 117:3463-74. PubMed
  • Handschin C, Chin S, Li P, Liu F, Maratos-Flier E, Lebrasseur NK, Yan Z, Spiegelman BM. Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals. J Biol Chem 2007; 282:30014-21. PubMed
  • J. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A 2007; 104:12017-22. PubMed
  • Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, Tavernier G, Langin D, Spiegelman BM. Transcriptional control of brown fat determination by PRDM16. Cell Metab 2007; 6:38-54. PubMed
  • Rohas LM, St-Pierre J, Uldry M, J. A fundamental system of cellular energy homeostasis regulated by PGC-1alpha. Proc Natl Acad Sci U S A 2007; 104:7933-8. PubMed
  • Girnun GD, Naseri E, Vafai SB, Qu L, Szwaya JD, Bronson R, Alberta JA, Spiegelman BM. Synergy between PPARgamma Ligands and Platinum-Based Drugs in Cancer. Cancer Cell 2007; 11:395-406. PubMed
  • Handschin C, Kobayashi YM, Chin S, Seale P, Campbell KP, Spiegelman BM. PGC-1alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy. Genes Dev 2007; 21:770-83. PubMed
  • Arany Z, Lebrasseur N, Morris C, Smith E, Yang W, Ma Y, Chin S, Spiegelman BM. The transcriptional coactivator PGC-1beta drives the formation of oxidative type IIX fibers in skeletal muscle. Cell Metab 2006; 5:35-46. PubMed
  • Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006; 444:847-53. PubMed
  • St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, J. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 2006; 127:397-408. PubMed
  • Kim R, Arihiro K, Emi M, Tanabe K, Osaki A. Potential role of HER-2; in primary breast tumor with bone metastasis. Oncol Rep 2006; 15:1477-84. PubMed
  • Rhee J, Ge H, Yang W, Fan M, Handschin C, Cooper M, Lin J, Li C, Spiegelman BM. Partnership of PGC-1{alpha} and HNF4{alpha} in the Regulation of Lipoprotein Metabolism. J Biol Chem 2006; 281:14683-90. PubMed
  • Uldry M, Yang W, St-Pierre J, Lin J, Seale P, Spiegelman BM. Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. Cell Metab 2006; 3:333-41. PubMed
  • Wang L, Liu J, Saha P, Huang J, Chan L, Spiegelman B, Moore DD. The orphan nuclear receptor SHP regulates PGC-1alpha expression and energy production in brown adipocytes. Cell Metab 2005; 2:227-38. PubMed
  • Handschin C, Lin J, Rhee J, Peyer AK, Chin S, Wu PH, Meyer UA, Spiegelman BM. Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1alpha. Cell 2005; 122:505-15. PubMed
  • Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, Mueller E, Benjamin T, Spiegelman BM, Sharp PA, Hopkins N, Yaffe MB. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 2005; 309:1074-8. PubMed
  • Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab 2005; 1:361-70. PubMed
  • Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu PH, Rybkin II, Shelton JM, Manieri M, Cinti S, Schoen FJ, Bassel-Duby R, Rosenzweig A, Ingwall JS, Spiegelman BM. Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab 2005; 1:259-71. PubMed
  • Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 2005; 434:113-8. PubMed
  • Chen Z, Torrens JI, Anand A, Spiegelman BM, Friedman JM. Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms. Cell Metab 2005; 1:93-106. PubMed
  • Drori S, Girnun GD, Tou L, Szwaya JD, Mueller E, Xia K, Kia X, Shivdasani RA, Spiegelman BM. Hic-5 regulates an epithelial program mediated by PPARgamma. Genes Dev 2005; 19:362-75. PubMed
  • Lin J, Yang R, Tarr PT, Wu PH, Handschin C, Li S, Yang W, Pei L, Uldry M, Tontonoz P, Newgard CB, Spiegelman BM. Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP. Cell 2005; 120:261-73. PubMed
  • Smith MR, Manola J, Kaufman DS, George D, Oh WK, Mueller E, Slovin S, Spiegelman B, Small E, Kantoff PW. Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy. Cancer 2004; 101:1569-74. PubMed
  • Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, J. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell 2004; 119:121-35. PubMed
  • Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D, Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM. Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci U S A 2004; 101:6570-5. PubMed
  • Cao W, Daniel KW, Robidoux J, Puigserver P, Medvedev AV, Bai X, Floering LM, Spiegelman BM, Collins S. p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol Cell Biol 2004; 24:3057-67. PubMed
  • Fan M, Rhee J, St-Pierre J, Handschin C, Puigserver P, Lin J, J. Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK. Genes Dev 2004; 18:278-89. PubMed
  • Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG. Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Mol Cell 2003; 12:1137-49. PubMed
  • Burstein HJ, Demetri GD, Mueller E, Sarraf P, Spiegelman BM, Winer EP. Use of the peroxisome proliferator-activated receptor (PPAR) gamma ligand troglitazone as treatment for refractory breast cancer: a phase II study. Breast Cancer Res Treat 2003; 79:391-7. PubMed
  • Mueller E, Drori S, Aiyer A, Yie J, Sarraf P, Chen H, Hauser S, Rosen ED, Ge K, Roeder RG, Spiegelman BM. Genetic analysis of adipogenesis through peroxisome proliferator-activated receptor gamma isoforms. J Biol Chem 2002; 277:41925-30. PubMed
  • Girnun GD, Smith WM, Drori S, Sarraf P, Mueller E, Eng C, Nambiar P, Rosenberg DW, Bronson RT, Edelmann W, Kucherlapati R, Gonzalez FJ, Spiegelman BM. APC-dependent suppression of colon carcinogenesis by PPARgamma. Proc Natl Acad Sci U S A 2002; 99:13771-6. PubMed
  • Kulke MH, Demetri GD, Sharpless NE, Ryan DP, Shivdasani R, Clark JS, Spiegelman BM, Kim H, Mayer RJ, Fuchs CS. A phase II study of troglitazone, an activator of the PPARgamma receptor, in patients with chemotherapy-resistant metastatic colorectal cancer. Cancer J 2002; 8:395-9. PubMed
  • Rich-Edwards JW, Spiegelman D, Garland M, Hertzmark E, Hunter DJ, Colditz GA, Willett WC, Wand H, Manson JE. Physical activity, body mass index, and ovulatory disorder infertility. Epidemiology 2002; 13:184-90. PubMed
  • Lin J, Puigserver P, Donovan J, Tarr P, Spiegelman BM. Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta ), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem 2001; 277:1645-8. PubMed
  • Coley JL, Msamanga GI, Fawzi MC, Kaaya S, Hertzmark E, Kapiga S, Spiegelman D, Hunter D, Fawzi WW. The association between maternal HIV-1 infection and pregnancy outcomes in Dar es Salaam, Tanzania. BJOG 2002; 108:1125-33. PubMed
  • Field AE, Wing RR, Manson JE, Spiegelman DL, Willett WC. Relationship of a large weight loss to long-term weight change among young and middle-aged US women. Int J Obes Relat Metab Disord 2001; 25:1113-21. PubMed
  • Moore KJ, Rosen ED, Fitzgerald ML, Randow F, Andersson LP, Altshuler D, Milstone DS, Mortensen RM, Spiegelman BM, Freeman MW. The role of PPAR-gamma in macrophage differentiation and cholesterol uptake. Nat Med 2001; 7:41-7. PubMed
  • Mueller E, Smith M, Sarraf P, Kroll T, Aiyer A, Kaufman DS, Oh W, Demetri G, Figg WD, Zhou XP, Eng C, Spiegelman BM, Kantoff PW. Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer. Proc Natl Acad Sci U S A 2000; 97:10990-5. PubMed
  • Kroll TG, Sarraf P, Pecciarini L, Chen CJ, Mueller E, Spiegelman BM, Fletcher JA. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected] Science 2000; 289:1357-60. PubMed
  • Monsalve M, Wu Z, Adelmant G, Puigserver P, Fan M, Spiegelman BM. Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1. Mol Cell 2000; 6:307-16. PubMed
  • Yoon JC, Chickering TW, Rosen ED, Dussault B, Qin Y, Soukas A, Friedman JM, Holmes WE, Spiegelman BM. Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. Mol Cell Biol 2000; 20:5343-9. PubMed
  • Wright HM, Clish CB, Mikami T, Hauser S, Yanagi K, Hiramatsu R, Serhan CN, Spiegelman BM. A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation. J Biol Chem 2000; 275:1873-7. PubMed
  • Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 1999; 4:611-7. PubMed
  • Castillo G, Brun RP, Rosenfield JK, Hauser S, Park CW, Troy AE, Wright ME, Spiegelman BM. An adipogenic cofactor bound by the differentiation domain of PPARgamma. EMBO J 1999; 18:3676-87. PubMed
  • Sarraf P, Mueller E, Smith WM, Wright HM, Kum JB, Aaltonen LA, de la Chapelle A, Spiegelman BM, Eng C. Loss-of-function mutations in PPAR gamma associated with human colon cancer. Mol Cell 1999; 3:799-804. PubMed
  • Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N, Spiegelman BM, Singer S. Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci U S A 1999; 96:3951-6. PubMed
  • Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 1998; 92:829-39. PubMed
  • Mueller E, Sarraf P, Tontonoz P, Evans RM, Martin KJ, Zhang M, Fletcher C, Singer S, Spiegelman BM. Terminal differentiation of human breast cancer through PPAR gamma. Mol Cell 1998; 1:465-70. PubMed
  • Kim JB, Sarraf P, Wright M, Yao KM, Mueller E, Solanes G, Lowell BB, Spiegelman BM. Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J Clin Invest 1998; 101:1-9. PubMed
  • Spiegelman BM. Peroxisome proliferator-activated receptor gamma: A key regulator of adipogenesis and systemic insulin sensitivity. Eur J Med Res 1998; 2:457-64. PubMed
  • Tontonoz P, Singer S, Forman BM, Sarraf P, Fletcher JA, Fletcher CD, Brun RP, Mueller E, Altiok S, Oppenheim H, Evans RM, Spiegelman BM. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor. Proc Natl Acad Sci U S A 1997; 94:237-41. PubMed
  • Spiegelman BM, Flier JS. Adipogenesis and obesity: rounding out the big picture. Cell 1996; 87:377-89. PubMed
  • Brun RP, Tontonoz P, Forman BM, Ellis R, Chen J, Evans RM, Spiegelman BM. Differential activation of adipogenesis by multiple PPAR isoforms. Genes Dev 1996; 10:974-84. PubMed
  • Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 1995; 83:803-12. PubMed
  • Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 1994; 79:1147-56. PubMed
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