DF/HCC Program Affiliation

Cancer Cell Biology
Cancer Genetics
Breast Cancer

DF/HCC Associations

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

• 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 May 25;316(5828):1198-202.
  17525341
• 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
  17420451
• 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.Cel
  17350581
• 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, Ka
  17287723
• 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 Nov 3;127(3):539-52.
  17081976
• 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 Jun 23;22(6):719-29.
  16793542
• Kim H, Livingston DM.A high mobility group protein binds to long CAG repeat tracts and establishes their chromatin organization in Saccharomyces cerevisiae.J Biol Chem 2006 Apr 9.
  16603770
• 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 Feb;9(2):121-32.
  16473279
• 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 Jan 1;20(1):34-46.
  16391231
• Muljo SA, Ansel KM, Kanellopoulou C, Livingston DM, Rao A, Rajewsky K.Aberrant T cell differentiation in the absence of Dicer.J Exp Med 2005 Jul 18;202(2):261-9.
  16009718
• Elshamy WM, Livingston DM.Promoter usage of BRCA1-IRIS.Nat Cell Biol 2005 Apr;7(4):326.
  15803127
• Samuelson AV, Narita M, Chan HM, Jin J, de Stanchina E, McCurrach ME, Narita M, Fuchs M, Livingston DM, Lowe SW.p400 is required for E1A to promote apoptosis.J Biol Chem 2005 Jun 10;280(23):21915-23.
  15741165
• 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 Feb 15;19(4):489-501.
  15713842
• Chan HM, Narita M, Lowe SW, Livingston DM.The p400 E1A-associated protein is a novel component of the p53 --> p21 senescence pathway.Genes Dev 2005 Jan 15;19(2):196-201.
  15655109
• ElShamy WM, Livingston DM.Identification of BRCA1-IRIS, a BRCA1 locus product.Nat Cell Biol 2004 Oct;6(10):954-67.
  15448696
• Taubert S, Gorrini C, Frank SR, Parisi T, Fuchs M, Chan HM, Livingston DM, Amati B.E2F-dependent histone acetylation and recruitment of the Tip60 acetyltransferase complex to chromatin in late G1.Mol Cell Biol 2004 May;24(10):4546-56.
  15121871
• Wilson CA, Ramos L, Villaseñor MR, Anders KH, Press MF, Clarke K, Karlan B, Chen JJ, Scully R, Livingston D, Zuch RH, Kanter MH, Cohen S, Calzone FJ, Slamon DJ.Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas.Nat Gen
  9988281
• Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G, Couch FJ, Weber BL, Ashley T, Livingston DM, Scully R.Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells.Mol Cell 1998 Sep;2(3
  9774970
• Livingston DM, Silver DP.Cancer: crossing over to drug resistance.Nature 2008 Feb 28;451(7182):1066-7.
  18305536
• 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
  17922014
• Gevry N, Chan HM, Laflamme L, Livingston DM, Gaudreau L.p21 transcription is regulated by differential localization of histone H2A.Z.Genes Dev 2007 Aug 1;21(15):1869-81.
  17671089
• Pageau GJ, Hall LL, Ganesan S, Livingston DM, Lawrence JB.The disappearing Barr body in breast and ovarian cancers.Nat Rev Cancer 2007 Aug;7(8):628-33.
  17611545
• 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 Feb;39(2):159-61.
  17200672
• 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 2005;70:93-
  16869742
• Kung AL, Zabludoff SD, France DS, Freedman SJ, Tanner EA, Vieira A, Cornell-Kennon S, Lee J, Wang B, Wang J, Memmert K, Naegeli HU, Petersen F, Eck MJ, Bair KW, Wood AW, Livingston DM.Small molecule blockade of transcriptional coactivation of the hypoxia-
  15261140
• 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 Jan 29;359(1441):123-8.
  15065664
• 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 Feb 24;101(8):2357-62.
  14983014
• Livingston DM.EMSY, a BRCA-2 partner in crime.Nat Med 2004 Feb;10(2):127-8.
  14760417
• Avni D, Yang H, Martelli F, Hofmann F, ElShamy WM, Ganesan S, Scully R, Livingston DM.Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage.Mol Cell 2003 Sep;12(3):735-46.
  14527418
• Grossman SR, Deato ME, Brignone C, Chan HM, Kung AL, Tagami H, Nakatani Y, Livingston DM.Polyubiquitination of p53 by a ubiquitin ligase activity of p300.Science 2003 Apr 11;300(5617):342-4.
  12690203
• 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 chro
  12419249
• Bassing CH, Chua KF, Sekiguchi J, Suh H, Whitlow SR, Fleming JC, Monroe BC, Ciccone DN, Yan C, Vlasakova K, Livingston DM, Ferguson DO, Scully R, Alt FW.Increased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX.Proc N
  12034884
• Freedman SJ, Sun ZY, Poy F, Kung AL, Livingston DM, Wagner G, Eck MJ.Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha.Proc Natl Acad Sci U S A 2002 Apr 16;99(8):5367-72.
  11959990
• Yang H, Williams BO, Hinds PW, Shih TS, Jacks T, Bronson RT, Livingston DM.Tumor suppression by a severely truncated species of retinoblastoma protein.Mol Cell Biol 2002 May;22(9):3103-10.
  11940667
• Joukov V, Chen J, Fox EA, Green JB, Livingston DM.Functional communication between endogenous BRCA1 and its partner, BARD1, during Xenopus laevis development.Proc Natl Acad Sci U S A 2001 Oct 9;98(21):12078-83.
  11593018
• Silver DP, Livingston DM.Self-excising retroviral vectors encoding the Cre recombinase overcome Cre-mediated cellular toxicity.Mol Cell 2001 Jul;8(1):233-43.
  11511376
• Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane WS, Nakatani Y, Livingston DM.The p400 complex is an essential E1A transformation target.Cell 2001 Aug 10;106(3):297-307.
  11509179
• Cantor SB, Bell DW, Ganesan S, Kass EM, Drapkin R, Grossman S, Wahrer DC, Sgroi DC, Lane WS, Haber DA, Livingston DM.BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function.Cell 2001 Apr 6;105(1):149-
  11301010
• Martelli F, Hamilton T, Silver DP, Sharpless NE, Bardeesy N, Rokas M, DePinho RA, Livingston DM, Grossman SR.p19ARF targets certain E2F species for degradation.Proc Natl Acad Sci U S A 2001 Apr 10;98(8):4455-60.
  11274364
• Gaubatz S, Lees JA, Lindeman GJ, Livingston DM.E2F4 is exported from the nucleus in a CRM1-dependent manner.Mol Cell Biol 2001 Feb;21(4):1384-92.
  11158323
• Tibbetts RS, Cortez D, Brumbaugh KM, Scully R, Livingston D, Elledge SJ, Abraham RT.Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress.Genes Dev 2000 Dec 1;14(23):2989-3002.
  11114888
• Scully R, Livingston DM.In search of the tumour-suppressor functions of BRCA1 and BRCA2.Nature 2000 Nov 23;408(6811):429-32.
  11100717
• Kung AL, Wang S, Klco JM, Kaelin WG, Livingston DM.Suppression of tumor growth through disruption of hypoxia-inducible transcription.Nat Med 2000 Dec;6(12):1335-40.
  11100117
• Eid JE, Kung AL, Scully R, Livingston DM.p300 interacts with the nuclear proto-oncoprotein SYT as part of the active control of cell adhesion.Cell 2000 Sep 15;102(6):839-48.
  11030627
• Wu X, Petrini JH, Heine WF, Weaver DT, Livingston DM, Chen J.Independence of R/M/N focus formation and the presence of intact BRCA1.Science 2000 Jul 7;289(5476):11.
  10928918
• Wu X, Ranganathan V, Weisman DS, Heine WF, Ciccone DN, O'Neill TB, Crick KE, Pierce KA, Lane WS, Rathbun G, Livingston DM, Weaver DT.ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response.Nature 2000 May 25;405(6785
  10839545
• Kung AL, Rebel VI, Bronson RT, Ch'ng LE, Sieff CA, Livingston DM, Yao TP.Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP.Genes Dev 2000 Feb 1;14(3):272-7.
  10673499
• Martelli F, Livingston DM.Regulation of endogenous E2F1 stability by the retinoblastoma family proteins.Proc Natl Acad Sci U S A 1999 Mar 16;96(6):2858-63.
  10077601
• Bhattacharya S, Michels CL, Leung MK, Arany ZP, Kung AL, Livingston DM.Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1.Genes Dev 1999 Jan 1;13(1):64-75.
  9887100
• Wang ZM, Yang H, Livingston DM.Endogenous E2F-1 promotes timely G0 exit of resting mouse embryo fibroblasts.Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15583-6.
  9861012
• Grossman SR, Perez M, Kung AL, Joseph M, Mansur C, Xiao ZX, Kumar S, Howley PM, Livingston DM.p300/MDM2 complexes participate in MDM2-mediated p53 degradation.Mol Cell 1998 Oct;2(4):405-15.
  9809062
• Gaubatz S, Wood JG, Livingston DM.Unusual proliferation arrest and transcriptional control properties of a newly discovered E2F family member, E2F-6.Proc Natl Acad Sci U S A 1998 Aug 4;95(16):9190-5.
  9689056
• Kawasaki H, Eckner R, Yao TP, Taira K, Chiu R, Livingston DM, Yokoyama KK.Distinct roles of the co-activators p300 and CBP in retinoic-acid-induced F9-cell differentiation.Nature 1998 May 21;393(6682):284-9.
  9607768
• Lindeman GJ, Dagnino L, Gaubatz S, Xu Y, Bronson RT, Warren HB, Livingston DM.A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting.Genes Dev 1998 Apr 15;12(8):1092-8.
  9553039
• Yao TP, Oh SP, Fuchs M, Zhou ND, Ch'ng LE, Newsome D, Bronson RT, Li E, Livingston DM, Eckner R.Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.Cell 1998 May 1;93(3):361-72.
  9590171
• Scully R, Chen J, Ochs RL, Keegan K, Hoekstra M, Feunteun J, Livingston DM.Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage.Cell 1997 Aug 8;90(3):425-35.
  9267023
• Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, Livingston DM, Parvin JD.BRCA1 is a component of the RNA polymerase II holoenzyme.Proc Natl Acad Sci U S A 1997 May 27;94(11):5605-10.
  9159119
• Lindeman GJ, Gaubatz S, Livingston DM, Ginsberg D.The subcellular localization of E2F-4 is cell-cycle dependent.Proc Natl Acad Sci U S A 1997 May 13;94(10):5095-100.
  9144196
• Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM.Association of BRCA1 with Rad51 in mitotic and meiotic cells.Cell 1997 Jan 24;88(2):265-75.
  9008167
• Lill NL, Tevethia MJ, Eckner R, Livingston DM, Modjtahedi N.p300 family members associate with the carboxyl terminus of simian virus 40 large tumor antigen.J Virol 1997 Jan;71(1):129-37.
  8985331
• Huang LE, Arany Z, Livingston DM, Bunn HF.Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit.J Biol Chem 1996 Dec 13;271(50):32253-9.
  8943284
• Hofmann F, Martelli F, Livingston DM, Wang Z.The retinoblastoma gene product protects E2F-1 from degradation by the ubiquitin-proteasome pathway.Genes Dev 1996 Dec 1;10(23):2949-59.
  8956996
• Arany Z, Huang LE, Eckner R, Bhattacharya S, Jiang C, Goldberg MA, Bunn HF, Livingston DM.An essential role for p300/CBP in the cellular response to hypoxia.Proc Natl Acad Sci U S A 1996 Nov 12;93(23):12969-73.
  8917528
• Yao TP, Ku G, Zhou N, Scully R, Livingston DM.The nuclear hormone receptor coactivator SRC-1 is a specific target of p300.Proc Natl Acad Sci U S A 1996 Oct 1;93(20):10626-31.
  8855229
• Bhattacharya S, Eckner R, Grossman S, Oldread E, Arany Z, D'Andrea A, Livingston DM.Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha.Nature 1996 Sep 26;383(6598):344-7.
  8848048
• Eckner R, Ludlow JW, Lill NL, Oldread E, Arany Z, Modjtahedi N, DeCaprio JA, Livingston DM, Morgan JA.Association of p300 and CBP with simian virus 40 large T antigen.Mol Cell Biol 1996 Jul;16(7):3454-64.
  8668161
• Xiao ZX, Ginsberg D, Ewen M, Livingston DM.Regulation of the retinoblastoma protein-related protein p107 by G1 cyclin-associated kinases.Proc Natl Acad Sci U S A 1996 May 14;93(10):4633-7.
  8643455
• Scully R, Ganesan S, Brown M, De Caprio JA, Cannistra SA, Feunteun J, Schnitt S, Livingston DM.Location of BRCA1 in human breast and ovarian cancer cells.Science 1996 Apr 5;272(5258):123-6.
  8600523
• Hofmann F, Livingston DM.Differential effects of cdk2 and cdk3 on the control of pRb and E2F function during G1 exit.Genes Dev 1996 Apr 1;10(7):851-61.
  8846921
• Krek W, Xu G, Livingston DM.Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint.Cell 1995 Dec 29;83(7):1149-58.
  8548802
• Wydner KL, Bhattacharya S, Eckner R, Lawrence JB, Livingston DM.Localization of human CREB-binding protein gene (CREBBP) to 16p13.2-p13.3 by fluorescence in situ hybridization.Genomics 1995 Nov 20;30(2):395-6.
  8586450