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Marcia C. Haigis, Ph.D.

TitleAssociate Professor of Cell Biology
InstitutionHarvard Medical School
DepartmentCell Biology
AddressHarvard Medical School
Cell Biology, Seeley Mudd Bldg 329
250 Longwood Ave
Boston MA 02115

 Mentoring 
 current student opportunities
Available: 10/01/12, Expires: 09/27/14

The Haigis laboratory is interested in understanding the links between mitochondrial dysfunction and cancer onset and progression. Mitochondria are dynamic organelles that provide cells with energy and are also a major site for reactive oxygen species production and stress response. Not surprisingly, mitochondrial dysfunction and aberrant metabolism have been implicated in metabolic diseases and several types of cancer.

Mammals have seven homologs of the protein deacetylase SIR2, three of which are found in mitochondria. Recent studies have shown that sirtuins are key regulators of mitochondrial function and energy production. Our lab is focused on understanding the links between sirtuins and tumor cell metabolism. The main goals of this research project will be: 1) to identify novel substrates of mitochondrial sirtuins and 2) to determine how aberrant sirtuin function may promote tumor cell metabolism. To accomplish these goals, our research integrates biochemistry, proteomics, cell biology and mouse genetics.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Bause AS, Matsui MS, Haigis MC. The Protein Deacetylase SIRT3 Prevents Oxidative Stress-induced Keratinocyte Differentiation. J Biol Chem. 2013 Dec 20; 288(51):36484-91.
    View in: PubMed
  2. Laurent G, de Boer VC, Finley LW, Sweeney M, Lu H, Schug TT, Cen Y, Jeong SM, Li X, Sauve AA, Haigis MC. SIRT4 Represses Peroxisome Proliferator-Activated Receptor a Activity To Suppress Hepatic Fat Oxidation. Mol Cell Biol. 2013 Nov; 33(22):4552-61.
    View in: PubMed
  3. Laurent G, German NJ, Saha AK, de Boer VC, Davies M, Koves TR, Dephoure N, Fischer F, Boanca G, Vaitheesvaran B, Lovitch SB, Sharpe AH, Kurland IJ, Steegborn C, Gygi SP, Muoio DM, Ruderman NB, Haigis MC. SIRT4 Coordinates the Balance between Lipid Synthesis and Catabolism by Repressing Malonyl CoA Decarboxylase. Mol Cell. 2013 Jun 6; 50(5):686-98.
    View in: PubMed
  4. Yang MH, Laurent G, Bause AS, Spang R, German N, Haigis MC, Haigis KM. HDAC6 and SIRT2 Regulate the Acetylation State and Oncogenic Activity of Mutant K-RAS. Mol Cancer Res. 2013 Sep; 11(9):1072-7.
    View in: PubMed
  5. Csibi A, Fendt SM, Li C, Poulogiannis G, Choo AY, Chapski DJ, Jeong SM, Dempsey JM, Parkhitko A, Morrison T, Henske EP, Haigis MC, Cantley LC, Stephanopoulos G, Yu J, Blenis J. The mTORC1 Pathway Stimulates Glutamine Metabolism and Cell Proliferation by Repressing SIRT4. Cell. 2013 May 9; 153(4):840-54.
    View in: PubMed
  6. Jeong SM, Xiao C, Finley LW, Lahusen T, Souza AL, Pierce K, Li YH, Wang X, Laurent G, German NJ, Xu X, Li C, Wang RH, Lee J, Csibi A, Cerione R, Blenis J, Clish CB, Kimmelman A, Deng CX, Haigis MC. SIRT4 Has Tumor-Suppressive Activity and Regulates the Cellular Metabolic Response to DNA Damage by Inhibiting Mitochondrial Glutamine Metabolism. Cancer Cell. 2013 Apr 15; 23(4):450-63.
    View in: PubMed
  7. Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, Kang Y, Fleming JB, Bardeesy N, Asara JM, Haigis MC, DePinho RA, Cantley LC, Kimmelman AC. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature. 2013 Apr 4; 496(7443):101-5.
    View in: PubMed
  8. Lee PC, Dodart JC, Aron L, Finley LW, Bronson RT, Haigis MC, Yankner BA, Harper JW. Altered social behavior and neuronal development in mice lacking the uba6-use1 ubiquitin transfer system. Mol Cell. 2013 Apr 25; 50(2):172-84.
    View in: PubMed
  9. Peserico A, Chiacchiera F, Grossi V, Matrone A, Latorre D, Simonatto M, Fusella A, Ryall JG, Finley LW, Haigis MC, Villani G, Puri PL, Sartorelli V, Simone C. A novel AMPK-dependent FoxO3A-SIRT3 intramitochondrial complex sensing glucose levels. Cell Mol Life Sci. 2013 Jun; 70(11):2015-29.
    View in: PubMed
  10. Sebastián C, Satterstrom FK, Haigis MC, Mostoslavsky R. From sirtuin biology to human diseases: an update. J Biol Chem. 2012 Dec 14; 287(51):42444-52.
    View in: PubMed
  11. Bause AS, Haigis MC. SIRT3 regulation of mitochondrial oxidative stress. Exp Gerontol. 2013 Jul; 48(7):634-9.
    View in: PubMed
  12. 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 Sep 4; 122(9):3088-100.
    View in: PubMed
  13. Inuzuka H, Gao D, Finley LW, Yang W, Wan L, Fukushima H, Chin YR, Zhai B, Shaik S, Lau AW, Wang Z, Gygi SP, Nakayama K, Teruya-Feldstein J, Toker A, Haigis MC, Pandolfi PP, Wei W. Acetylation-dependent regulation of Skp2 function. Cell. 2012 Jul 6; 150(1):179-93.
    View in: PubMed
  14. Finley LW, Haigis MC. Metabolic regulation by SIRT3: implications for tumorigenesis. Trends Mol Med. 2012 Sep; 18(9):516-23.
    View in: PubMed
  15. Yang MH, Nickerson S, Kim ET, Liot C, Laurent G, Spang R, Philips MR, Shan Y, Shaw DE, Bar-Sagi D, Haigis MC, Haigis KM. Regulation of RAS oncogenicity by acetylation. Proc Natl Acad Sci U S A. 2012 Jul 3; 109(27):10843-8.
    View in: PubMed
  16. Haigis MC, Deng CX, Finley LW, Kim HS, Gius D. SIRT3 is a mitochondrial tumor suppressor: a scientific tale that connects aberrant cellular ROS, the Warburg effect, and carcinogenesis. Cancer Res. 2012 May 15; 72(10):2468-72.
    View in: PubMed
  17. Cerletti M, Jang YC, Finley LW, Haigis MC, Wagers AJ. Short-term calorie restriction enhances skeletal muscle stem cell function. Cell Stem Cell. 2012 May 4; 10(5):515-9.
    View in: PubMed
  18. Garcia-Cao I, Song MS, Hobbs RM, Laurent G, Giorgi C, de Boer VC, Anastasiou D, Ito K, Sasaki AT, Rameh L, Carracedo A, Vander Heiden MG, Cantley LC, Pinton P, Haigis MC, Pandolfi PP. Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell. 2012 Mar 30; 149(1):49-62.
    View in: PubMed
  19. Finley LW, Lee J, Souza A, Desquiret-Dumas V, Bullock K, Rowe GC, Procaccio V, Clish CB, Arany Z, Haigis MC. Skeletal muscle transcriptional coactivator PGC-1a mediates mitochondrial, but not metabolic, changes during calorie restriction. Proc Natl Acad Sci U S A. 2012 Feb 21; 109(8):2931-6.
    View in: PubMed
  20. De Raedt T, Walton Z, Yecies JL, Li D, Chen Y, Malone CF, Maertens O, Jeong SM, Bronson RT, Lebleu V, Kalluri R, Normant E, Haigis MC, Manning BD, Wong KK, Macleod KF, Cichowski K. Exploiting cancer cell vulnerabilities to develop a combination therapy for ras-driven tumors. Cancer Cell. 2011 Sep 13; 20(3):400-13.
    View in: PubMed
  21. Finley LW, Haas W, Desquiret-Dumas V, Wallace DC, Procaccio V, Gygi SP, Haigis MC. Succinate dehydrogenase is a direct target of sirtuin 3 deacetylase activity. PLoS One. 2011; 6(8):e23295.
    View in: PubMed
  22. Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, Bause A, Li Y, Stommel JM, Dell'antonio G, Mautner J, Tonon G, Haigis M, Shirihai OS, Doglioni C, Bardeesy N, Kimmelman AC. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 2011 Apr 1; 25(7):717-29.
    View in: PubMed
  23. Finley LW, Carracedo A, Lee J, Souza A, Egia A, Zhang J, Teruya-Feldstein J, Moreira PI, Cardoso SM, Clish CB, Pandolfi PP, Haigis MC. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1a destabilization. Cancer Cell. 2011 Mar 8; 19(3):416-28.
    View in: PubMed
  24. Srivastava S, Haigis MC. Role of sirtuins and calorie restriction in neuroprotection: implications in Alzheimer's and Parkinson's diseases. Curr Pharm Des. 2011; 17(31):3418-33.
    View in: PubMed
  25. Haigis MC, Yankner BA. The aging stress response. Mol Cell. 2010 Oct 22; 40(2):333-44.
    View in: PubMed
  26. Verdin E, Hirschey MD, Finley LW, Haigis MC. Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling. Trends Biochem Sci. 2010 Dec; 35(12):669-75.
    View in: PubMed
  27. Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010; 5:253-95.
    View in: PubMed
  28. Lomb DJ, Laurent G, Haigis MC. Sirtuins regulate key aspects of lipid metabolism. Biochim Biophys Acta. 2010 Aug; 1804(8):1652-7.
    View in: PubMed
  29. Nakagawa T, Lomb DJ, Haigis MC, Guarente L. SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell. 2009 May 1; 137(3):560-70.
    View in: PubMed
  30. Finley LW, Haigis MC. The coordination of nuclear and mitochondrial communication during aging and calorie restriction. Ageing Res Rev. 2009 Jul; 8(3):173-88.
    View in: PubMed
  31. Haigis KM, Kendall KR, Wang Y, Cheung A, Haigis MC, Glickman JN, Niwa-Kawakita M, Sweet-Cordero A, Sebolt-Leopold J, Shannon KM, Settleman J, Giovannini M, Jacks T. Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon. Nat Genet. 2008 May; 40(5):600-8.
    View in: PubMed
  32. Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese RV, Weissman S, Verdin E, Schwer B. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol. 2007 Dec; 27(24):8807-14.
    View in: PubMed
  33. Haigis MC, Guarente LP. Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006 Nov 1; 20(21):2913-21.
    View in: PubMed
  34. Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, Valenzuela DM, Yancopoulos GD, Karow M, Blander G, Wolberger C, Prolla TA, Weindruch R, Alt FW, Guarente L. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell. 2006 Sep 8; 126(5):941-54.
    View in: PubMed
  35. Blander G, Olejnik J, Krzymanska-Olejnik E, McDonagh T, Haigis M, Yaffe MB, Guarente L. SIRT1 shows no substrate specificity in vitro. J Biol Chem. 2005 Mar 18; 280(11):9780-5.
    View in: PubMed
  36. Dickson KA, Haigis MC, Raines RT. Ribonuclease inhibitor: structure and function. Prog Nucleic Acid Res Mol Biol. 2005; 80:349-74.
    View in: PubMed
  37. Leissring MA, Farris W, Wu X, Christodoulou DC, Haigis MC, Guarente L, Selkoe DJ. Alternative translation initiation generates a novel isoform of insulin-degrading enzyme targeted to mitochondria. Biochem J. 2004 Nov 1; 383(Pt. 3):439-46.
    View in: PubMed
  38. Lin SJ, Ford E, Haigis M, Liszt G, Guarente L. Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev. 2004 Jan 1; 18(1):12-6.
    View in: PubMed
  39. Blander G, de Oliveira RM, Conboy CM, Haigis M, Guarente L. Superoxide dismutase 1 knock-down induces senescence in human fibroblasts. J Biol Chem. 2003 Oct 3; 278(40):38966-9.
    View in: PubMed
  40. Haigis MC, Kurten EL, Raines RT. Ribonuclease inhibitor as an intracellular sentry. Nucleic Acids Res. 2003 Feb 1; 31(3):1024-32.
    View in: PubMed
  41. Haigis MC, Raines RT. Secretory ribonucleases are internalized by a dynamin-independent endocytic pathway. J Cell Sci. 2003 Jan 15; 116(Pt 2):313-24.
    View in: PubMed
  42. Abel RL, Haigis MC, Park C, Raines RT. Fluorescence assay for the binding of ribonuclease A to the ribonuclease inhibitor protein. Anal Biochem. 2002 Jul 1; 306(1):100-7.
    View in: PubMed
  43. Haigis MC, Haag ES, Raines RT. Evolution of ribonuclease inhibitor by exon duplication. Mol Biol Evol. 2002 Jun; 19(6):959-63.
    View in: PubMed
  44. Umezawa N, Gelman MA, Haigis MC, Raines RT, Gellman SH. Translocation of a beta-peptide across cell membranes. J Am Chem Soc. 2002 Jan 23; 124(3):368-9.
    View in: PubMed
  45. Haigis MC, Kurten EL, Abel RL, Raines RT. KFERQ sequence in ribonuclease A-mediated cytotoxicity. J Biol Chem. 2002 Mar 29; 277(13):11576-81.
    View in: PubMed
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