Photo of Pere Puigserver,  PhD

Pere Puigserver, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 582-7977


pere_puigserver@dfci.harvard.edu

Pere Puigserver, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Cell Biology, Harvard Medical School
  • Professor, Cancer Biology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Puigserver Laboratory investigates broad aspects of fundamental metabolic and energetic processes in mammals that are necessary for cell survival and specific biological function. We focus on the molecular mechanisms by which mammalian cells sense, communicate, and respond to nutrients.

Studies from our group have identified new basic and evolutionary conserved metabolic circuitries that involve nutrient signaling to gene expression programs associated with cellular metabolic reprogramming. Components of these circuitries are dysregulated in metabolic diseases, cancer, and age-associated diseases and represent therapeutic targets.

The Lab's research program pursues fundamental biological and disease-relevant questions such as:

*What are the molecular components that sense and transmit nutrient signals to reprogram mammalian cells?

*What are the molecular components that sense signals to coordinate the supply of proteins for mitochondrial biogenesis, dynamics and function?

*What are the genetic and epigenetic mechanisms underlying metabolic reprogramming and plasticity in tumor cells?

The Puigserver Lab's research combines and applies a variety of biochemical, cellular, genetic, chemical biology, metabolic and screening approaches both in cell culture and whole animals to identify the molecular mechanisms by which mammalian cells sense, communicate, and respond to nutrients. In particular, we have a close collaboration with the Broad Institute in chemical biology to identify small compounds involved in nutrient sensing and metabolic reprogramming in a variety of mammalian cell types.

 

Publications

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  • Soustek MS, Puigserver P. Interrupting synoviolin play at the ER: a plausible action to elevate mitochondrial energetics and silence obesity. EMBO J 2015. PubMed
  • Rines AK, Verdeguer F, Puigserver P. Adenosine activates thermogenic adipocytes. Cell Res 2015; 25:155-6. PubMed
  • Lee Y, Dominy JE, Choi YJ, Jurczak M, Tolliday N, Camporez JP, Chim H, Lim JH, Ruan HB, Yang X, Vazquez F, Sicinski P, Shulman GI, Puigserver P. Cyclin D1-Cdk4 controls glucose metabolism independently of cell cycle progression. Nature 2014. PubMed
  • Lim JH, Luo C, Vazquez F, Puigserver P. Targeting Mitochondrial Oxidative Metabolism in Melanoma Causes Metabolic Compensation through Glucose and Glutamine Utilization. Cancer Res 2014. PubMed
  • Tabata M, Rodgers JT, Hall JA, Lee Y, Jedrychowski MP, Gygi SP, Puigserver P. Cdc2-Like Kinase 2 Suppresses Hepatic Fatty Acid Oxidation and Ketogenesis Through Disruption of the PGC-1留 and MED1 Complex. Diabetes 2014; 63:1519-32. PubMed
  • Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, Pirinen E, Pulinilkunnil TC, Gong F, Wang YC, Cen Y, Sauve AA, Asara JM, Peroni OD, Monia BP, Bhanot S, Alhonen L, Puigserver P, Kahn BB. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature 2014; 508:258-62. PubMed
  • Hall JA, Tabata M, Rodgers JT, Puigserver P. USP7 attenuates hepatic gluconeogenesis through modulation of FoxO1 gene promoter occupancy. Mol Endocrinol 2014. PubMed
  • Verdeguer F, Blättler SM, Cunningham JT, Hall JA, Chim H, Puigserver P. Decreased genetic dosage of hepatic Yin Yang 1 causes diabetic-like symptoms. Mol Endocrinol 2014; 28:308-16. 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
  • Dominy J, Puigserver P, Cantó C. In vivo measurement of the acetylation state of sirtuin substrates as a proxy for sirtuin activity. Methods Mol Biol 2013; 1077:217-37. 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
  • Carracedo A, Weiss D, Leliaert AK, Bhasin M, de Boer VC, Laurent G, Adams AC, Sundvall M, Song SJ, Ito K, Finley LS, Egia A, Libermann T, Gerhart-Hines Z, Puigserver P, Haigis MC, Maratos-Flier E, Richardson AL, Schafer ZT, Pandolfi PP. A metabolic prosurvival role for PML in breast cancer. J Clin Invest 2012; 122:3088-100. PubMed
  • Blättler SM, Verdeguer F, Liesa M, Cunningham JT, Vogel RO, Chim H, Liu H, Romanino K, Shirihai OS, Vazquez F, Rüegg MA, Shi Y, Puigserver P. Defective mitochondrial morphology and bioenergetic function in mice lacking the transcription factor Yin Yang 1 in skeletal muscle. Mol Cell Biol 2012; 32:3333-46. PubMed
  • Rodgers JT, Vogel RO, Puigserver P. Clk2 and B56硫 mediate insulin-regulated assembly of the PP2A phosphatase holoenzyme complex on Akt. Mol Cell 2011; 41:471-9. PubMed
  • Dominy JE, Puigserver P. Nuclear FoxO1 inflames insulin resistance. EMBO J 2010; 29:4068-9. PubMed
  • Dominy JE, Lee Y, Gerhart-Hines Z, Puigserver P. Nutrient-dependent regulation of PGC-1alpha's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5. Biochim Biophys Acta 2010; 1804:1676-83. PubMed
  • Walker AK, Yang F, Jiang K, Ji JY, Watts JL, Purushotham A, Boss O, Hirsch ML, Ribich S, Smith JJ, Israelian K, Westphal CH, Rodgers JT, Shioda T, Elson SL, Mulligan P, Najafi-Shoushtari H, Black JC, Thakur JK, Kadyk LC, Whetstine JR, Mostoslavsky R, Puigserver P, Li X, Dyson NJ, Hart AC, Näär AM. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev 2010; 24:1403-17. PubMed
  • Rodgers JT, Haas W, Gygi SP, Puigserver P. Cdc2-like kinase 2 is an insulin-regulated suppressor of hepatic gluconeogenesis. Cell Metab 2010; 11:23-34. PubMed
  • Cheng Z, Guo S, Copps K, Dong X, Kollipara R, Rodgers JT, Depinho RA, Puigserver P, White MF. Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nat Med 2009; 15:1307-11. PubMed
  • Schafer ZT, Grassian AR, Song L, Jiang Z, Gerhart-Hines Z, Irie HY, Gao S, Puigserver P, Brugge JS. Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 2009; 461:109-13. PubMed
  • Kelly TJ, Lerin C, Haas W, Gygi SP, Puigserver P. GCN5-mediated transcriptional control of the metabolic coactivator PGC-1beta through lysine acetylation. J Biol Chem 2009; 284:19945-52. PubMed
  • Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009; 458:1056-60. PubMed
  • Rodgers JT, Puigserver P. Insulin resistance: beta-arrestin development. Cell Res 2009; 19:275-6. PubMed
  • Housley MP, Udeshi ND, Rodgers JT, Shabanowitz J, Puigserver P, Hunt DF, Hart GW. A PGC-1alpha-O-GlcNAc transferase complex regulates FoxO transcription factor activity in response to glucose. J Biol Chem 2009; 284:5148-57. PubMed
  • Suchankova G, Nelson LE, Gerhart-Hines Z, Kelly M, Gauthier MS, Saha AK, Ido Y, Puigserver P, Ruderman NB. Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells. Biochem Biophys Res Commun 2008; 378:836-41. PubMed
  • Coste A, Louet JF, Lagouge M, Lerin C, Antal MC, Meziane H, Schoonjans K, Puigserver P, O'Malley BW, Auwerx J. The genetic ablation of SRC-3 protects against obesity and improves insulin sensitivity by reducing the acetylation of PGC-1{alpha}. Proc Natl Acad Sci U S A 2008; 105:17187-92. PubMed
  • Housley MP, Rodgers JT, Udeshi ND, Kelly TJ, Shabanowitz J, Hunt DF, Puigserver P, Hart GW. O-GlcNAc regulates FoxO activation in response to glucose. J Biol Chem 2008; 283:16283-92. PubMed
  • Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P. Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett 2007; 582:46-53. PubMed
  • Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature 2007; 450:736-40. PubMed
  • Rodgers JT, Puigserver P. Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1. Proc Natl Acad Sci U S A 2007; 104:12861-6. PubMed
  • Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J 2007; 26:3169-79. PubMed
  • Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R, Alt FW, Wu Z, Puigserver P. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J 2007; 26:1913-23. PubMed
  • Rodgers JT, Puigserver P. Receptor feasts on sugar and cholesterol. Nat Med 2007; 13:128-9. PubMed
  • Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006; 127:1109-22. PubMed
  • Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006; 444:337-42. PubMed
  • Cha SH, Rodgers JT, Puigserver P, Chohnan S, Lane MD. Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: Role of PGC-1alpha. Proc Natl Acad Sci U S A 2006; 103:15410-5. PubMed
  • Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, Zhao W, Thiyagarajan M, MacGrogan D, Rodgers JT, Puigserver P, Sadoshima J, Deng H, Pedrini S, Gandy S, Sauve AA, Pasinetti GM. Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem 2006; 281:21745-54. PubMed
  • Lerin C, Rodgers JT, Kalume DE, Kim SH, Pandey A, Puigserver P. GCN5 acetyltransferase complex controls glucose metabolism through transcriptional repression of PGC-1alpha. Cell Metab 2006; 3:429-38. PubMed
  • Rodgers JT, Puigserver P. Certainly can't live without this: SIRT6. Cell Metab 2006; 3:77-8. PubMed
  • Puigserver P, Rodgers JT. Foxa2, a novel transcriptional regulator of insulin sensitivity. Nat Med 2006; 12:38-9. 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, Tarr PT, Yang R, Rhee J, Puigserver P, Newgard CB, Spiegelman BM. PGC-1beta in the regulation of hepatic glucose and energy metabolism. J Biol Chem 2003; 278:30843-8. PubMed
  • Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstråle M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 2003; 34:267-73. PubMed
  • Yoon JC, Xu G, Deeney JT, Yang SN, Rhee J, Puigserver P, Levens AR, Yang R, Zhang CY, Lowell BB, Berggren PO, Newgard CB, Bonner-Weir S, Weir G, Spiegelman BM. Suppression of beta cell energy metabolism and insulin release by PGC-1alpha. Dev Cell 2003; 5:73-83. PubMed
  • Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D, Spiegelman BM. Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 2003; 423:550-5. PubMed
  • Rhee J, Inoue Y, Yoon JC, Puigserver P, Fan M, Gonzalez FJ, Spiegelman BM. Regulation of hepatic fasting response by PPARgamma coactivator-1alpha (PGC-1): requirement for hepatocyte nuclear factor 4alpha in gluconeogenesis. Proc Natl Acad Sci U S A 2003; 100:4012-7. PubMed
  • Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr. Rev. 2003; 24:78-90. PubMed
  • Tritos NA, Mastaitis JW, Kokkotou EG, Puigserver P, Spiegelman BM, Maratos-Flier E. Characterization of the peroxisome proliferator activated receptor coactivator 1 alpha (PGC 1alpha) expression in the murine brain. Brain Res 2003; 961:255-60. PubMed
  • Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 2002; 418:797-801. 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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