Photo of David M. Livingston,  MD

David M. Livingston, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3074
Fax: (617) 632-4381


david_livingston@dfci.harvard.edu

David M. Livingston, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Genetics, Harvard Medical School
  • Emil Frei Professor of Medicine, Medicine, Harvard Medical School
  • Chairman, Executive Committee for Research, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • Member, Clinical Science Coordinating Committee
  • Member, Center Scientific Council
  • Deputy Director, Dana-Farber/Harvard Cancer Center, Executive Committee

Research Abstract

My research program is aimed at understanding the functional properties of four sets of nuclear proteins, each of which plays a major role in the suppression by human cells of certain transformed/neoplastic characteristics. They are the pocket protein family (pRB, p107, p130); p300 and CBP; p400 and TRRAP; and BRCA1 and 2. Analysis of the functions of BRCA1 and 2 as breast/ovarian cancer suppressing elements serve as our link to the Breast Cancer Program, and the work on the other three sets of transformation suppressing proteins underlie our participation in the Cancer Cell Biology Program. Futhermore, our laboratory contributes to an ongoing nodal point interaction between these two Programs. We are also working on converting elements of recent discovery of p300/CBP function into new screens for small molecule agents that interfere with hypoxia-driven tumor survival/proliferation responses.

Publications

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  • Wang H, Bierie B, Li AG, Pathania S, Toomire K, Dimitrov SD, Liu B, Gelman R, Giobbie-Hurder A, Feunteun J, Polyak K, Livingston DM. BRCA1/FANCD2/BRG1-Driven DNA Repair Stabilizes the Differentiation State of Human Mammary Epithelial Cells. Mol Cell 2016. PubMed
  • Brown M, Chinnaiyan A, Farsetti A, Livingston DM, Loda M, Schuele R, Mihich E. 26th Pezcoller symposium: cancers driven by hormones. Cancer Res 2015; 75:1177-80. PubMed
  • White EA, Kramer RE, Hwang JH, Pores Fernando AT, Naetar N, Hahn WC, Roberts TM, Schaffhausen BS, Livingston DM, Howley PM. Papillomavirus E7 oncoproteins share functions with polyomavirus small T antigens. J Virol 2015; 89:2857-65. PubMed
  • Hatchi E, Skourti-Stathaki K, Ventz S, Pinello L, Yen A, Kamieniarz-Gdula K, Dimitrov S, Pathania S, McKinney KM, Eaton ML, Kellis M, Hill SJ, Parmigiani G, Proudfoot NJ, Livingston DM. BRCA1 recruitment to transcriptional pause sites is required for R-loop-driven DNA damage repair. Mol Cell 2015; 57:636-47. PubMed
  • Baratta MG, Schinzel AC, Zwang Y, Bandopadhayay P, Bowman-Colin C, Kutt J, Curtis J, Piao H, Wong LC, Kung AL, Beroukhim R, Bradner JE, Drapkin R, Hahn WC, Liu JF, Livingston DM. An in-tumor genetic screen reveals that the BET bromodomain protein, BRD4, is a potential therapeutic target in ovarian carcinoma. Proc Natl Acad Sci U S A 2015; 112:232-7. PubMed
  • Hu Y, Petit SA, Ficarro SB, Toomire KJ, Xie A, Lim E, Cao SA, Park E, Eck MJ, Scully R, Brown M, Marto JA, Livingston DM. PARP1-driven poly-ADP-ribosylation regulates BRCA1 function in homologous recombination-mediated DNA repair. 2014. PubMed
  • Smith JA, Haberstroh FS, White EA, Livingston DM, DeCaprio JA, Howley PM. SMCX and components of the TIP60 complex contribute to E2 regulation of the HPV E6/E7 promoter. Virology 2014; 468-470C:311-21. PubMed
  • Hill SJ, Clark AP, Silver DP, Livingston DM. BRCA1 pathway function in basal-like breast cancer cells. Mol Cell Biol 2014; 34:3828-42. PubMed
  • Hill SJ, Rolland T, Adelmant G, Xia X, Owen MS, Dricot A, Zack TI, Sahni N, Jacob Y, Hao T, McKinney KM, Clark AP, Reyon D, Tsai SQ, Joung JK, Beroukhim R, Marto JA, Vidal M, Gaudet S, Hill DE, Livingston DM. Systematic screening reveals a role for BRCA1 in the response to transcription-associated DNA damage. Genes Dev 2014; 28:1957-75. PubMed
  • Naetar N, Soundarapandian V, Litovchick L, Goguen KL, Sablina AA, Bowman-Colin C, Sicinski P, Hahn WC, DeCaprio JA, Livingston DM. PP2A-mediated regulation of Ras signaling in G2 is essential for stable quiescence and normal G1 length. Mol Cell 2014. PubMed
  • Pathania S, Bade S, Le Guillou M, Burke K, Reed R, Bowman-Colin C, Su Y, Ting DT, Polyak K, Richardson AL, Feunteun J, Garber JE, Livingston DM. BRCA1 haploinsufficiency for replication stress suppression in primary cells. Nat Commun 2014; 5:5496. PubMed
  • Dimitrov SD, Lu D, Naetar N, Hu Y, Pathania S, Kanellopoulou C, Livingston DM. Physiological modulation of endogenous BRCA1 p220 abundance suppresses DNA damage during the cell cycle. Genes Dev 2013; 27:2274-91. PubMed
  • Bowman-Colin C, Xia B, Bunting S, Klijn C, Drost R, Bouwman P, Fineman L, Chen X, Culhane AC, Cai H, Rodig SJ, Bronson RT, Jonkers J, Nussenzweig A, Kanellopoulou C, Livingston DM. Palb2 synergizes with Trp53 to suppress mammary tumor formation in a model of inherited breast cancer. Proc Natl Acad Sci U S A 2013. PubMed
  • Jirawatnotai S, Hu Y, Livingston DM, Sicinski P. Proteomic identification of a direct role for cyclin d1 in DNA damage repair. Cancer Res 2012; 72:4289-93. PubMed
  • Ciccia A, Nimonkar AV, Hu Y, Hajdu I, Achar YJ, Izhar L, Petit SA, Adamson B, Yoon JC, Kowalczykowski SC, Livingston DM, Haracska L, Elledge SJ. Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress. Mol Cell 2012; 47:396-409. PubMed
  • Silver DP, Livingston DM. Mechanisms of BRCA1 tumor suppression. 2012; 2:679-84. PubMed
  • Hu Y, Scully R, Sobhian B, Xie A, Shestakova E, Livingston DM. RAP80-directed tuning of BRCA1 homologous recombination function at ionizing radiation-induced nuclear foci. Genes Dev 2011; 25:685-700. PubMed
  • Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, Pouchet C, Gilbert L, O'Brien PK, Serfas K, Broderick P, Houlston RS, Lesueur F, Bonora E, Muljo S, Schimke RN, Bouron-Dal Soglio D, Arseneau J, Schultz KA, Priest JR, Nguyen VH, Harach HR, Livingston DM, Foulkes WD, Tischkowitz M. DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. JAMA 2011; 305:68-77. PubMed
  • Bernards R, Filipowicz W, Livingston DM, Mihich E. Twenty-second annual Pezcoller Symposium: RNA biology and cancer. Cancer Res 2010; 70:10034-7. PubMed
  • Joukov V, De Nicolo A, Rodriguez A, Walter JC, Livingston DM. Centrosomal protein of 192 kDa (Cep192) promotes centrosome-driven spindle assembly by engaging in organelle-specific Aurora A activation. Proc Natl Acad Sci U S A 2010; 107:21022-7. PubMed
  • O'Donovan PJ, Livingston DM. BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair. Carcinogenesis 2010; 31:961-7. PubMed
  • Sheng Q, Liu X, Fleming E, Yuan K, Piao H, Chen J, Moustafa Z, Thomas RK, Greulich H, Schinzel A, Zaghlul S, Batt D, Ettenberg S, Meyerson M, Schoeberl B, Kung AL, Hahn WC, Drapkin R, Livingston DM, Liu JF. An activated ErbB3/NRG1 autocrine loop supports in vivo proliferation in ovarian cancer cells. Cancer Cell 2010; 17:298-310. PubMed
  • Mihich E, Pandolfi PP, Livingston D. Twenty-first annual Pezcoller Symposium: Unconventional Therapeutic Targets in Cancer. Cancer Res 2010; 70:14-7. PubMed
  • Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF, Schinzel AC, Sandy P, Meylan E, Scholl C, Fröhling S, Chan EM, Sos ML, Michel K, Mermel C, Silver SJ, Weir BA, Reiling JH, Sheng Q, Gupta PB, Wadlow RC, Le H, Hoersch S, Wittner BS, Ramaswamy S, Livingston DM, Sabatini DM, Meyerson M, Thomas RK, Lander ES, Mesirov JP, Root DE, Gilliland DG, Jacks T, Hahn WC. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 2009; 462:108-12. PubMed
  • Karanja KK, Livingston DM. C-terminal Flap Endonuclease (rad27) Mutations: Lethal Interactions With a DNA Ligase I Mutation (cdc9-p) and Suppression by Proliferating Cell Nuclear Antigen (POL30) in Saccharomyces cerevisiae. Genetics 2009; 183:63-78. PubMed
  • Livingston DM. Cancer. Complicated supercomplexes. Science 2009; 324:602-3. PubMed
  • Kim H, Livingston DM. Suppression of a DNA polymerase delta mutation by the absence of the high mobility group protein Hmo1 in Saccharomyces cerevisiae. Curr Genet 2009; 55:127-38. PubMed
  • Howley PM,Livingston DM. Small DNA tumor viruses: large contributors to biomedical sciences. Virology 2009; 384:256-9. PubMed
  • Kanellopoulou C,Muljo SA,Dimitrov SD,Chen X,Colin C,Plath K,Livingston DM. X chromosome inactivation in the absence of Dicer. Proc Natl Acad Sci U S A 2009; 106:1122-7. PubMed
  • Erkko H,Dowty JG,Nikkila J,Syrjakoski K,Mannermaa A,Pylkas K,Southey MC,Holli K,Kallioniemi A,Jukkola-Vuorinen A,Kataja V,Kosma VM,Xia B,Livingston DM,Winqvist R,Hopper JL. Penetrance analysis of the PALB2 c.1592delT founder mutation. Clin Cancer Res 2008; 14:4667-71. PubMed
  • Livingston DM, Silver DP. Cancer: crossing over to drug resistance. Nature 2008; 451:1066-7. PubMed
  • Pujana MA, Han JD, Starita LM, Stevens KN, Tewari M, Ahn JS, Rennert G, Moreno V, Kirchhoff T, Gold B, Assmann V, Elshamy WM, Rual JF, Levine D, Rozek LS, Gelman RS, Gunsalus KC, Greenberg RA, Sobhian B, Bertin N, Venkatesan K, Ayivi-Guedehoussou N, Sole X, Hernandez P, Lazaro C, Nathanson KL, Weber BL, Cusick ME, Hill DE, Offit K, Livingston DM, Gruber SB, Parvin JD, Vidal M. Network modeling links breast cancer susceptibility and centrosome dysfunction. Nat Genet 2007; 39:1338-49. PubMed
  • Pageau GJ, Hall LL, Ganesan S, Livingston DM, Lawrence JB. The disappearing Barr body in breast and ovarian cancers. Nat Rev Cancer 2007; 7:628-33. PubMed
  • Gevry N, Chan HM, Laflamme L, Livingston DM, Gaudreau L. p21 transcription is regulated by differential localization of histone H2A.Z. Genes Dev 2007; 21:1869-81. PubMed
  • Sobhian B, Shao G, Lilli DR, Culhane AC, Moreau LA, Xia B, Livingston DM, Greenberg RA. RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science 2007; 316:1198-202. PubMed
  • Tischkowitz M, Xia B, Sabbaghian N, Reis-Filho JS, Hamel N, Li G, van Beers EH, Li L, Khalil T, Quenneville LA, Omeroglu A, Poll A, Lepage P, Wong N, Nederlof PM, Ashworth A, Tonin PN, Narod SA, Livingston DM, Foulkes WD. Analysis of PALB2/FANCN-associated breast cancer families. Proc Natl Acad Sci U S A 2007; 104:6788-93. PubMed
  • Erkko H, Xia B, Nikkila J, Schleutker J, Syrjakoski K, Mannermaa A, Kallioniemi A, Pylkas K, Karppinen SM, Rapakko K, Miron A, Sheng Q, Li G, Mattila H, Bell DW, Haber DA, Grip M, Reiman M, Jukkola-Vuorinen A, Mustonen A, Kere J, Aaltonen LA, Kosma VM, Kataja V, Soini Y, Drapkin RI, Livingston DM, Winqvist R. A recurrent mutation in PALB2 in Finnish cancer families. Nature 2007; 446:316-9. PubMed
  • Silver DP, Dimitrov SD, Feunteun J, Gelman R, Drapkin R, Lu SD, Shestakova E, Velmurugan S, Denunzio N, Dragomir S, Mar J, Liu X, Rottenberg S, Jonkers J, Ganesan S, Livingston DM. Further evidence for BRCA1 communication with the inactive X chromosome. Cell 2007; 128:991-1002. PubMed
  • Xia B, Dorsman JC, Ameziane N, de Vries Y, Rooimans MA, Sheng Q, Pals G, Errami A, Gluckman E, Llera J, Wang W, Livingston DM, Joenje H, de Winter JP. Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Nat Genet 2007; 39:159-61. PubMed
  • Joukov V, Groen AC, Prokhorova T, Gerson R, White E, Rodriguez A, Walter JC, Livingston DM. The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly. Cell 2006; 127:539-52. PubMed
  • Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, Liu X, Jasin M, Couch FJ, Livingston DM. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell 2006; 22:719-29. PubMed
  • Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S. X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell 2006; 9:121-32. PubMed
  • Greenberg RA, Sobhian B, Pathania S, Cantor SB, Nakatani Y, Livingston DM. Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes. Genes Dev 2006; 20:34-46. PubMed
  • Kanellopoulou C, Muljo SA, Kung AL, Ganesan S, Drapkin R, Jenuwein T, Livingston DM, Rajewsky K. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 2005; 19:489-501. PubMed
  • Ganesan S, Richardson AL, Wang ZC, Iglehart JD, Miron A, Feunteun J, Silver D, Livingston DM. Abnormalities of the Inactive X Chromosome Are a Common Feature of BRCA1 Mutant and Sporadic Basal-like Breast Cancer. Cold Spring Harb Symp Quant Biol 2006; 70:93-7. PubMed
  • Cantor S, Drapkin R, Zhang F, Lin Y, Han J, Pamidi S, Livingston DM. The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations. Proc Natl Acad Sci U S A 2004; 101:2357-62. PubMed
  • Ganesan S, Silver DP, Drapkin R, Greenberg R, Feunteun J, Livingston DM. Association of BRCA1 with the inactive X chromosome and XIST RNA. Philos Trans R Soc Lond B Biol Sci 2004; 359:123-8. PubMed
  • Ganesan S, Silver DP, Greenberg RA, Avni D, Drapkin R, Miron A, Mok SC, Randrianarison V, Brodie S, Salstrom J, Rasmussen TP, Klimke A, Marrese C, Marahrens Y, Deng CX, Feunteun J, Livingston DM. BRCA1 supports XIST RNA concentration on the inactive X chromosome. Cell 2002; 111:393-405. PubMed
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