Bruce Spiegelman

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism
    Christophe Handschin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Endocr Rev 27:728-35. 2006
  2. doi UCP1 deficiency causes brown fat respiratory chain depletion and sensitizes mitochondria to calcium overload-induced dysfunction.
    Lawrence Kazak
    Proc Natl Acad Sci U S A . 2017
  3. pmc Thrap3 docks on phosphoserine 273 of PPARγ and controls diabetic gene programming
    Jang Hyun Choi
    Department of Biological Sciences, Ulsan National Institute of Science and Technology UNIST, Ulsan 689 798, Korea
    Genes Dev 28:2361-9. 2014
  4. pmc Sensitivity of lipid metabolism and insulin signaling to genetic alterations in hepatic peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression
    Jennifer L Estall
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA, USA
    Diabetes 58:1499-508. 2009
  5. pmc Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex
    Shingo Kajimura
    Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nature 460:1154-8. 2009
  6. pmc Transcriptional control of preadipocyte determination by Zfp423
    Rana K Gupta
    Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 464:619-23. 2010
  7. pmc Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5
    Jang Hyun Choi
    Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 466:451-6. 2010
  8. pmc Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation
    Jang Hyun Choi
    Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 477:477-81. 2011
  9. pmc A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
    Pontus Boström
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 481:463-8. 2012
  10. pmc Se-Jin Lee, myostatin discoverer, elected to the National Academy of Science
    David J Glass
    Novartis Institutes for BioMedical Research, 100 Technology Square, RM4210, Cambridge, MA 02139, USA
    Skelet Muscle 2:11. 2012

Research Grants

Detail Information

Publications117 found, 100 shown here

  1. ncbi Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism
    Christophe Handschin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Endocr Rev 27:728-35. 2006
    ..Recent studies have elucidated the function of the PGC-1 coactivators in different tissues and have highlighted the implications of PGC-1 dysregulation in diseases such as diabetes, obesity, cardiomyopathy, or neurodegeneration...
  2. doi UCP1 deficiency causes brown fat respiratory chain depletion and sensitizes mitochondria to calcium overload-induced dysfunction.
    Lawrence Kazak
    Proc Natl Acad Sci U S A . 2017
    ..This finding should be carefully considered when using this mouse model to examine the role of UCP1 in physiology...
  3. pmc Thrap3 docks on phosphoserine 273 of PPARγ and controls diabetic gene programming
    Jang Hyun Choi
    Department of Biological Sciences, Ulsan National Institute of Science and Technology UNIST, Ulsan 689 798, Korea
    Genes Dev 28:2361-9. 2014
    ..These data indicate that Thrap3 plays a crucial role in controlling diabetic gene programming and may provide opportunities for the development of new therapeutics for obesity and type 2 diabetes. ..
  4. pmc Sensitivity of lipid metabolism and insulin signaling to genetic alterations in hepatic peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression
    Jennifer L Estall
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA, USA
    Diabetes 58:1499-508. 2009
    ..However, how moderate changes in PGC-1alpha activity affect metabolism and energy homeostasis has yet to be determined...
  5. pmc Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex
    Shingo Kajimura
    Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nature 460:1154-8. 2009
    ..These data indicate that the PRDM16-C/EBP-beta complex initiates brown fat formation from myoblastic precursors, and may provide opportunities for the development of new therapeutics for obesity and type-2 diabetes...
  6. pmc Transcriptional control of preadipocyte determination by Zfp423
    Rana K Gupta
    Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 464:619-23. 2010
    ..This study identifies Zfp423 as a transcriptional regulator of preadipocyte determination...
  7. pmc Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARgamma by Cdk5
    Jang Hyun Choi
    Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 466:451-6. 2010
    ....
  8. pmc Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation
    Jang Hyun Choi
    Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 477:477-81. 2011
    ..Unlike TZDs, SR1664 also does not interfere with bone formation in culture. These data illustrate that new classes of antidiabetes drugs can be developed by specifically targeting the Cdk5-mediated phosphorylation of PPARγ...
  9. pmc A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
    Pontus Boström
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 481:463-8. 2012
    ..This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise...
  10. pmc Se-Jin Lee, myostatin discoverer, elected to the National Academy of Science
    David J Glass
    Novartis Institutes for BioMedical Research, 100 Technology Square, RM4210, Cambridge, MA 02139, USA
    Skelet Muscle 2:11. 2012
    ..He also determined the primary binding receptor for myostatin, and has characterized additional transforming growth factor-β family members acting in this pathway...
  11. pmc Banting Lecture 2012: Regulation of adipogenesis: toward new therapeutics for metabolic disease
    Bruce M Spiegelman
    Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Diabetes 62:1774-82. 2013
    ..Understanding the regulation of adipose tissue, white, brown, and beige, can potentially lead to the development of a new generation of therapeutics for diabetes prevention and treatment...
  12. ncbi Peroxisome proliferator-activated receptor gamma: A key regulator of adipogenesis and systemic insulin sensitivity
    B M Spiegelman
    Dana Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Eur J Med Res 2:457-64. 1997
    ..Furthermore, PPARgamma and other adipogenic transcription factors provide a focus for beginning to understand how various hormones and metabolites influence the development of this tissue in vivo...
  13. ncbi PPAR-gamma: adipogenic regulator and thiazolidinedione receptor
    B M Spiegelman
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Diabetes 47:507-14. 1998
    ....
  14. ncbi Regulation of adipogenesis and energy balance by PPARgamma and PGC-1
    B M Spiegelman
    Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Int J Obes Relat Metab Disord 24:S8-10. 2000
    ..The PGC-1 dependent program includes both mitochondrial biogenesis and tissue-specific expression of uncoupling proteins...
  15. ncbi Adipogenesis and obesity: rounding out the big picture
    B M Spiegelman
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 87:377-89. 1996
  16. pmc Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha
    E Hu
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 92:9856-60. 1995
    ..These factors have an ability to inhibit myogenesis that is temporally and functionally separate from their ability to stimulate adipogenesis...
  17. pmc Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation
    J C Yoon
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 20:5343-9. 2000
    ..Alterations in nutrition and leptin administration are found to modulate the PGAR expression in vivo. Taken together, these data suggest a possible role for PGAR in the regulation of systemic lipid metabolism or glucose homeostasis...
  18. ncbi Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor
    P Tontonoz
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
    Cell 79:1147-56. 1994
    ....
  19. ncbi Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1
    Z Wu
    Dana Farber Cancer Institute, and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 98:115-24. 1999
    ..These data elucidate a pathway that directly links external physiological stimuli to the regulation of mitochondrial biogenesis and function...
  20. ncbi Activation of PPARgamma coactivator-1 through transcription factor docking
    P Puigserver
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 286:1368-71. 1999
    ..Thus, transcription factor docking switches on the activity of a coactivator protein...
  21. ncbi mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer
    P Tontonoz
    Dana Farber Cancer Institute, Boston, Massachusetts
    Genes Dev 8:1224-34. 1994
    ....
  22. ncbi Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein
    G S Hotamisligil
    Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA CA 92093, USA
    Science 274:1377-9. 1996
    ..These results indicate that aP2 is central to the pathway that links obesity to insulin resistance, possibly by linking fatty acid metabolism to expression of TNF-alpha...
  23. ncbi Inhibition of adipogenesis through MAP kinase-mediated phosphorylation of PPARgamma
    E Hu
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 274:2100-3. 1996
    ..These results indicate that covalent modification of PPARgamma by serum and growth factors is a major regulator of the balance between cell growth and differentiation in the adipose cell lineage...
  24. ncbi Loss-of-function mutations in PPAR gamma associated with human colon cancer
    P Sarraf
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 3:799-804. 1999
    ..These data indicate that colon cancer in humans is associated with loss-of-function mutations in PPAR gamma...
  25. ncbi Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1
    P Puigserver
    Dana Farber Cancer Institute, Department of Cell Biology, Boston, MA 02115, USA
    Mol Cell 8:971-82. 2001
    ..These data illustrate a direct thermogenic action of cytokines and p38 MAP kinase through the transcriptional coactivator PGC-1...
  26. pmc Analysis of a tissue-specific enhancer: ARF6 regulates adipogenic gene expression
    R A Graves
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
    Mol Cell Biol 12:1202-8. 1992
    ....
  27. pmc Dual DNA binding specificity of ADD1/SREBP1 controlled by a single amino acid in the basic helix-loop-helix domain
    J B Kim
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    Mol Cell Biol 15:2582-8. 1995
    ..These data illustrate that ADD1/SREBP1 has dual DNA sequence specificity controlled by a single amino acid residue; this dual specificity may provide a novel mechanism to coordinate different pathways of lipid metabolism...
  28. pmc ADD1: a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation
    P Tontonoz
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
    Mol Cell Biol 13:4753-9. 1993
    ..These data suggest that ADD1 plays a role in the regulation of determination- and differentiation-specific gene expression in adipocytes...
  29. ncbi Differential activation of adipogenesis by multiple PPAR isoforms
    R P Brun
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 10:974-84. 1996
    ....
  30. ncbi A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis
    P Puigserver
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 92:829-39. 1998
    ..These results indicate that PGC-1 plays a key role in linking nuclear receptors to the transcriptional program of adaptive thermogenesis...
  31. pmc DEF-1, a novel Src SH3 binding protein that promotes adipogenesis in fibroblastic cell lines
    F J King
    Department of Cancer Biology, The Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Mol Cell Biol 19:2330-7. 1999
    ..These results suggest that DEF-1 is an important component of a signal transduction process that is involved in the differentiation of fibroblasts and possibly of other types of cells...
  32. pmc An adipogenic cofactor bound by the differentiation domain of PPARgamma
    G Castillo
    Dana Farber Cancer Institute, 44 Binney Street Boston, MA 02115, USA
    EMBO J 18:3676-87. 1999
    ..These results suggest that interactions between PGC-2, a receptor isoform-selective cofactor and PPARgamma contribute to the adipogenic action of this receptor...
  33. ncbi Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy
    Matthew R Smith
    Division of Hematology and Medical Oncology, Massachusetts General Hospital, Boston 02114, USA
    Cancer 101:1569-74. 2004
    ....
  34. ncbi Targeting of nonexpressed genes in embryonic stem cells via homologous recombination
    R S Johnson
    Dana Farber Cancer Institute, Boston, MA
    Science 245:1234-6. 1989
    ..These studies demonstrate the feasibility of altering genes in ES cells that are expressed in a tissue-specific manner in the mouse, in order to study their function at later developmental stages...
  35. pmc Adipocyte-specific transcription factor ARF6 is a heterodimeric complex of two nuclear hormone receptors, PPAR gamma and RXR alpha
    P Tontonoz
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115
    Nucleic Acids Res 22:5628-34. 1994
    ..These results suggest that PPAR gamma 2 serves a unique function among PPAR family members as an important regulator of adipocyte-specific gene expression...
  36. ncbi Adipocyte differentiation: a transcriptional regulatory cascade
    R P Brun
    Dana Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Curr Opin Cell Biol 8:826-32. 1996
    ..Furthermore, these factors provide a focus for beginning to understand how various hormones and metabolites influence the development of adipose tissue in vivo...
  37. ncbi Differential regulation of the p80 tumor necrosis factor receptor in human obesity and insulin resistance
    G S Hotamisligil
    Department of Nutrition, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Diabetes 46:451-5. 1997
    ..56, P < 0.001). These results suggest that TNFR2 might play a role in human obesity by modulating the actions of TNF-alpha...
  38. ncbi Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity
    Z Wu
    Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Mol Cell 3:151-8. 1999
    ..These results define multiple roles for C/EBP alpha in adipogenesis and show that cross-regulation between PPAR gamma and C/EBP alpha is a key component of the transcriptional control of this cell lineage...
  39. ncbi PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro
    E D Rosen
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA
    Mol Cell 4:611-7. 1999
    ..In vitro, the differentiation of ES cells into fat is shown to be dependent on PPAR gamma gene dosage. These data provide direct evidence that PPAR gamma is essential for the formation of fat...
  40. ncbi Towards a molecular understanding of adaptive thermogenesis
    B B Lowell
    Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 404:652-60. 2000
    ..Here we explore these developments in relation to classical physiological views of adaptive thermogenesis...
  41. ncbi PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]
    T G Kroll
    Department of Pathology, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Science 289:1357-60. 2000
    ..The experiments demonstrate an oncogenic role for PPARgamma and suggest that PAX8-PPARgamma1 may be useful in the diagnosis and treatment of thyroid carcinoma...
  42. ncbi The role of PPAR-gamma in macrophage differentiation and cholesterol uptake
    K J Moore
    Lipid Metabolism Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Med 7:41-7. 2001
    ....
  43. ncbi Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
    J C Yoon
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 413:131-8. 2001
    ..These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver...
  44. ncbi PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
    Vamsi K Mootha
    Whitehead Institute MIT Center for Genome Research, Cambridge, Massachusetts, USA
    Nat Genet 34:267-73. 2003
    ..Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments...
  45. ncbi Vascular endothelial growth factor. Regulation by cell differentiation and activated second messenger pathways
    K P Claffey
    Dana Farber Cancer Institute, Boston, Massachusetts
    J Biol Chem 267:16317-22. 1992
    ....
  46. pmc Normal peripheral T-cell function in c-Fos-deficient mice
    J Jain
    Division of Tumor Virology, Dana Farber Cancer Institute, Boston, Massachusetts 02115
    Mol Cell Biol 14:1566-74. 1994
    ..Our results suggest that other Fos family members may be capable of substituting functionally for c-Fos during T-cell development and cytokine gene transcription in activated T cells...
  47. ncbi Tumor necrosis factor (TNF)-alpha inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase
    P Peraldi
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 271:13018-22. 1996
    ..These data strongly suggest that TNF-alpha inhibits insulin signaling via stimulation of p55 TNFR and sphingomyelinase activity, which results in the production of an inhibitory form of IRS-1...
  48. ncbi Molecular regulation of adipogenesis
    E D Rosen
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Annu Rev Cell Dev Biol 16:145-71. 2000
    ..Emphasis is placed, where possible, on in vivo studies with the hope that the results discussed may one day shed light on basic questions of cellular growth and differentiation in addition to possible benefits in human health...
  49. ncbi Adipsin and complement factor D activity: an immune-related defect in obesity
    B S Rosen
    Dana Farber Cancer Institute, Boston, MA
    Science 244:1483-7. 1989
    ..These results suggest that adipsin and the alternative pathway of complement may play an unexpected but important role in the regulation of systemic energy balance in vivo...
  50. ncbi Adrenal glucocorticoids regulate adipsin gene expression in genetically obese mice
    B M Spiegelman
    Dana Farber Cancer Institute, Boston, Massachusetts 02115
    J Biol Chem 264:1811-5. 1989
    ..Quantitative analysis of these experiments suggests that other as yet unknown neuroendocrine factors also function to suppress adipsin in obesity...
  51. ncbi AdipoQ is a novel adipose-specific gene dysregulated in obesity
    E Hu
    Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    J Biol Chem 271:10697-703. 1996
    ..Whereas the biological function of this polypeptide is presently unknown, the tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue...
  52. ncbi Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1
    M Monsalve
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 6:307-16. 2000
    ..PGC-1 can alter the processing of an mRNA, but only when it is loaded onto the promoter of the gene. These data demonstrate the coordinated regulation of RNA transcription and processing through PGC-1...
  53. pmc Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1
    L F Michael
    Dana-Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:3820-5. 2001
    ..These data indicate that PGC-1 is a coactivator of MEF2C and can control the level of endogenous GLUT4 gene expression in muscle...
  54. pmc Tumor necrosis factor alpha inhibits signaling from the insulin receptor
    G S Hotamisligil
    Dana Farber Cancer Institute, Boston, MA 02115
    Proc Natl Acad Sci U S A 91:4854-8. 1994
    ..These results show that TNF-alpha directly interferes with the signaling of insulin through its receptor and consequently blocks biological actions of insulin...
  55. pmc Growth and differentiation of embryonic stem cells that lack an intact c-fos gene
    S J Field
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115
    Proc Natl Acad Sci U S A 89:9306-10. 1992
    ..We conclude that despite a large body of literature suggesting an important role for c-fos in cell growth and differentiation, in at least some cell types this gene is not essential for these processes...
  56. ncbi c-fos is required for malignant progression of skin tumors
    E Saez
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 82:721-32. 1995
    ..These results demonstrate that a member of the AP-1 family of transcription factors is required for the development of a malignant tumor...
  57. pmc Targeted disruption of the c-fos gene demonstrates c-fos-dependent and -independent pathways for gene expression stimulated by growth factors or oncogenes
    E Hu
    Dana Farber Cancer Institute, Boston, MA 02115
    EMBO J 13:3094-103. 1994
    ..These results also imply that c-fos may play an important regulatory role in the invasive behavior of malignant tumors, independent of any role this proto-oncogene might play in cell growth per se...
  58. pmc C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway
    Evan D Rosen
    Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Genes Dev 16:22-6. 2002
    ..These results indicate that C/EBPalpha and PPARgamma participate in a single pathway of fat cell development with PPARgamma being the proximal effector of adipogenesis...
  59. ncbi Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis
    Kai Ge
    Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 417:563-7. 2002
    ..These data indicate that TRAP220 acts, via the TRAP complex, as a PPAR gamma(2)-selective coactivator and, accordingly, that it is specific for one fibroblast differentiation pathway (adipogenesis) relative to another (myogenesis)...
  60. ncbi Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres
    Jiandie Lin
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 418:797-801. 2002
    ..These data indicate that PGC-1 alpha is a principal factor regulating muscle fibre type determination...
  61. ncbi Genetic analysis of adipogenesis through peroxisome proliferator-activated receptor gamma isoforms
    Elisabetta Mueller
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:41925-30. 2002
    ..Analyses involving coactivator binding and transcriptional assays indicate that PPARgamma2 has an enhanced ability to bind components of the DRIP/TRAP complex, coactivators required for fat differentiation...
  62. pmc APC-dependent suppression of colon carcinogenesis by PPARgamma
    Geoffrey D Girnun
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, One Jimmy Fund Way, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:13771-6. 2002
    ..This finding suggests a potentially important use for PPARgamma ligands as chemopreventative agents in colon cancer...
  63. ncbi A phase II study of troglitazone, an activator of the PPARgamma receptor, in patients with chemotherapy-resistant metastatic colorectal cancer
    Matthew H Kulke
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer J 8:395-9. 2002
    ..We therefore assessed the efficacy of troglitazone in the treatment of metastatic colon cancer in humans...
  64. ncbi Characterization of the peroxisome proliferator activated receptor coactivator 1 alpha (PGC 1alpha) expression in the murine brain
    Nicholas A Tritos
    Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215, USA
    Brain Res 961:255-60. 2003
    ..Hence, PGC-1alpha is widely expressed in the rodent brain, but is not regulated by states of caloric deficiency, leptin, obesity or cold exposure. Its functional role in the brain requires further study...
  65. ncbi PPARgamma ligands: taking Ppart in chemoprevention
    Geoffrey D Girnun
    Gastroenterology 124:564-7. 2003
  66. pmc Regulation of hepatic fasting response by PPARgamma coactivator-1alpha (PGC-1): requirement for hepatocyte nuclear factor 4alpha in gluconeogenesis
    James Rhee
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:4012-7. 2003
    ..These data illustrate the involvement of PGC-1alpha in several aspects of the hepatic fasting response and show that HNF4alpha is a critical component of PGC-1alpha-mediated gluconeogenesis...
  67. ncbi Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells
    Julie St-Pierre
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:26597-603. 2003
    ..Together, these data indicate that PGC-1alpha and PGC-1beta profoundly alter mitochondrial metabolism and suggest that these proteins are likely to play different physiological functions...
  68. ncbi Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction
    Pere Puigserver
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 423:550-5. 2003
    ..We conclude that FOXO1 and PGC-1alpha interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis...
  69. pmc An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle
    Christoph Handschin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:7111-6. 2003
    ..Furthermore, these data suggest an autofeedback loop whereby the calcium-signaling pathway may result in a stable induction of PGC-1alpha, contributing to the relatively stable nature of muscle fiber-type determination...
  70. ncbi Use of the peroxisome proliferator-activated receptor (PPAR) gamma ligand troglitazone as treatment for refractory breast cancer: a phase II study
    Harold J Burstein
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Breast Cancer Res Treat 79:391-7. 2003
    ..To evaluate the therapeutic effects of the peroxisome proliferator-activated receptor (PPAR) gamma activating ligand, troglitazone, in patients with refractory metastatic breast cancer...
  71. ncbi Suppression of beta cell energy metabolism and insulin release by PGC-1alpha
    J Cliff Yoon
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA
    Dev Cell 5:73-83. 2003
    ..These results strongly suggest that PGC-1alpha plays a key functional role in the beta cell and is involved in the pathogenesis of the diabetic phenotype...
  72. pmc Muscle-specific PPARgamma-deficient mice develop increased adiposity and insulin resistance but respond to thiazolidinediones
    Andrew W Norris
    Research Division, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA
    J Clin Invest 112:608-18. 2003
    ..The tissue crosstalk mediating these effects is perhaps due to altered lipid metabolism in muscle...
  73. pmc Targeted elimination of peroxisome proliferator-activated receptor gamma in beta cells leads to abnormalities in islet mass without compromising glucose homeostasis
    Evan D Rosen
    Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Mol Cell Biol 23:7222-9. 2003
    ....
  74. ncbi Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha
    Annika E Wallberg
    Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA
    Mol Cell 12:1137-49. 2003
    ....
  75. pmc Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK
    Melina Fan
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 18:278-89. 2004
    ..The discovery of p160MBP as a PGC-1alpha regulator has important implications for the understanding of energy balance and diabetes...
  76. pmc p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene
    Wenhong Cao
    Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 24:3057-67. 2004
    ..In conclusion, our findings illustrate that by orchestrating the activity of multiple transcription factors, p38 MAPK is a central mediator of the cAMP signaling mechanism of brown fat that promotes thermogenesis...
  77. pmc Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle
    Vamsi K Mootha
    The Eli and Edythe L Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139 1561, USA
    Proc Natl Acad Sci U S A 101:6570-5. 2004
    ....
  78. ncbi Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice
    Jiandie Lin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 119:121-35. 2004
    ..These data illustrate a central role for PGC-1alpha in the control of energy metabolism but also reveal novel systemic compensatory mechanisms and pathogenic effects of impaired energy homeostasis...
  79. ncbi Biological control through regulated transcriptional coactivators
    Bruce M Spiegelman
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115 USA
    Cell 119:157-67. 2004
    ..These kinetic aspects suggest opportunities and concerns as coactivators become targets of therapeutic intervention...
  80. ncbi Hyperlipidemic effects of dietary saturated fats mediated through PGC-1beta coactivation of SREBP
    Jiandie Lin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 120:261-73. 2005
    ..These data suggest a mechanism through which dietary saturated fats can stimulate hyperlipidemia and atherogenesis...
  81. pmc Hic-5 regulates an epithelial program mediated by PPARgamma
    Stavit Drori
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 19:362-75. 2005
    ..These results indicate that Hic5 is an important component in determining an epithelial differentiation program induced by PPARgamma...
  82. ncbi Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1
    Joseph T Rodgers
    Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nature 434:113-8. 2005
    ..Thus, we have identified a molecular mechanism whereby SIRT1 functions in glucose homeostasis as a modulator of PGC-1alpha. These findings have strong implications for the basic pathways of energy homeostasis, diabetes and lifespan...
  83. ncbi Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms
    Zhu Chen
    Laboratory of Molecular Genetics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Cell Metab 1:93-106. 2005
    ..These data indicate that Krox20 is necessary for adipogenesis and that, when overexpressed, Krox20 potently stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms...
  84. ncbi Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle
    Zoltan Arany
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell Metab 1:259-71. 2005
    ..As mice lacking PGC-1alpha age, cardiac dysfunction becomes evident in vivo. These data indicate that PGC-1alpha is vital for the heart to meet increased demands for ATP and work in response to physiological stimuli...
  85. ncbi Metabolic control through the PGC-1 family of transcription coactivators
    Jiandie Lin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell Metab 1:361-70. 2005
    ..These actions also raise new opportunities for the development of novel therapeutics...
  86. ncbi TAZ, a transcriptional modulator of mesenchymal stem cell differentiation
    Jeong Ho Hong
    Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18 580, Cambridge, MA 02139, USA
    Science 309:1074-8. 2005
    ..These results indicate that TAZ functions as a molecular rheostat that modulates MSC differentiation...
  87. ncbi Nutritional regulation of hepatic heme biosynthesis and porphyria through PGC-1alpha
    Christoph Handschin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 122:505-15. 2005
    ..These data show that PGC-1alpha links nutritional status to heme biosynthesis and acute hepatic porphyria...
  88. ncbi Partnership of PGC-1alpha and HNF4alpha in the regulation of lipoprotein metabolism
    James Rhee
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, One Jimmy Fund Way, Boston, MA 02115, USA
    J Biol Chem 281:14683-90. 2006
    ..These data point to a crucial role for the PGC-1alpha/HNF4alpha partnership in hepatic lipoprotein metabolism...
  89. ncbi Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation
    Marc Uldry
    Dana Farber Cancer Institute, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA
    Cell Metab 3:333-41. 2006
    ....
  90. pmc Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-gamma coactivator 1alpha
    Zoltan Arany
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:10086-91. 2006
    ..Moreover, the data suggest that elevating PGC-1alpha activity may have therapeutic potential in the treatment of heart failure...
  91. pmc Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1alpha/LRP130 complex
    Marcus P Cooper
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Genes Dev 20:2996-3009. 2006
    ..These data link LRP130 and PGC-1alpha to defective hepatic energy homeostasis in LSFC, and reveal a novel regulatory mechanism of glucose homeostasis...
  92. pmc PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription
    Marco Sandri
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:16260-5. 2006
    ..Thus, the high levels of PGC-1alpha in dark and exercising muscles can explain their resistance to atrophy, and the rapid fall in PGC-1alpha during atrophy should enhance the FoxO-dependent loss of muscle mass...
  93. ncbi Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators
    Julie St-Pierre
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 127:397-408. 2006
    ..These studies reveal that PGC-1alpha is a broad and powerful regulator of ROS metabolism, providing a potential target for the therapeutic manipulation of these important endogenous toxins...
  94. ncbi 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...
  95. pmc Hypomorphic mutation of PGC-1beta causes mitochondrial dysfunction and liver insulin resistance
    Claudia R Vianna
    Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell Metab 4:453-64. 2006
    ..Importantly, these abnormalities do not cause insulin resistance in skeletal muscle but cause substantially reduced insulin action in the liver...
  96. pmc Adipocytes as regulators of energy balance and glucose homeostasis
    Evan D Rosen
    Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Centre, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Nature 444:847-53. 2006
    ..Furthermore, the rational manipulation of adipose physiology is a promising avenue for therapy of these conditions...
  97. pmc PGC-1alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy
    Christoph Handschin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 21:770-83. 2007
    ..Thus, control of PGC-1alpha levels in skeletal muscle could represent a novel avenue to prevent or treat DMD...
  98. pmc Synergy between PPARgamma ligands and platinum-based drugs in cancer
    Geoffrey D Girnun
    Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 11:395-406. 2007
    ..These data strongly suggest combining PPARgamma agonists and platinum-based drugs for the treatment of certain human cancers...
  99. pmc AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha
    Sibylle Jäger
    Dana Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:12017-22. 2007
    ..These data indicate that AMPK phosphorylation of PGC-1alpha initiates many of the important gene regulatory functions of AMPK in skeletal muscle...
  100. pmc Transcriptional control of brown fat determination by PRDM16
    Patrick Seale
    Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA
    Cell Metab 6:38-54. 2007
    ..PRDM16 activates brown fat cell identity at least in part by simultaneously activating PGC-1alpha and PGC-1beta through direct protein binding. These data indicate that PRDM16 can control the determination of brown fat fate...
  101. ncbi Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1alpha muscle-specific knock-out animals
    Christoph Handschin
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 282:30014-21. 2007
    ..Our data demonstrate a critical role for PGC-1alpha in maintenance of normal fiber type composition and of muscle fiber integrity following exertion...

Research Grants2

  1. TRANSCRIPTIONAL CONTROL OF COLON CANCER THROUGH PPARY
    Bruce Spiegelman; Fiscal Year: 2004
    ..Since PPAR-gamma ligands are clinically available now, this work may provide a framework in which to contemplate new therapeutic approaches to colon cancer. ..