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 PPARγ. Nature 2015; 517:391-5. PubMed
  • White JP, Wrann CD, Rao RR, Nair SK, Jedrychowski MP, You JS, Martínez-Redondo V, Gygi SP, Ruas JL, Hornberger TA, Wu Z, Glass DJ, Piao X, Spiegelman BM. G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy. Proc Natl Acad Sci U S A 2014. PubMed
  • Choi JH, Choi SS, Kim ES, Jedrychowski MP, Yang YR, Jang HJ, Suh PG, Banks AS, Gygi SP, Spiegelman BM. Thrap3 docks on phosphoserine 273 of PPARγ and controls diabetic gene programming. Genes Dev 2014. 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
  • Lo JC, Ljubicic S, Leibiger B, Kern M, Leibiger IB, Moede T, Kelly ME, Chatterjee Bhowmick D, Murano I, Cohen P, Banks AS, Khandekar MJ, Dietrich A, Flier JS, Cinti S, Blüher M, Danial NN, Berggren PO, Spiegelman BM. Adipsin is an adipokine that improves β cell function in diabetes. Cell 2014; 158:41-53. 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-1α/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. PGC1α 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; author reply 352. 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
  • 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
  • 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
  • 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
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