Photo of David M. Weinstock,  MD

David M. Weinstock, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4245
Fax: (617) 632-6380

David M. Weinstock, MD

Dana-Farber Cancer Institute


  • Associate Professor, Medicine, Harvard Medical School
  • Attending Physician, Medical Oncology Service, Dana-Farber Cancer Institute
  • Associate Member, Cancer Biology, Broad Institute of MIT and Harvard


Research Abstract

Despite decades of effort, the tumor genome remains ripe for discovery. The laboratory utilizes both functional and sequencing approaches to identify and characterize oncogene alterations directly from tumor specimens. Newly-identified alterations are further assayed using a variety of in vitro and in vivo methods, with the ultimate goal of translating discoveries into novel therapies.

Our initial efforts identified CRLF2, a previously obscure cytokine receptor, as an essential oncogene in 5-10% of adult and pediatric acute lymphoblastic leukemia (ALL). We subsequently demonstrated that agents targeting HSP90 or BRD4 are active in human leukemias with CRLF2 alterations, defined the mechanisms of CRLF2 locus rearrangement and clarified mechanisms that link CRLF2 alterations with Down Syndrome. These findings have inspired clinical trials in both children and adults with this poor-risk subset of ALL.

In a second line of inquiry, we are assaying the nature and determinants of DNA repair in mammalian cells. These studies extend from tumor specimens, where we have characterized a novel oncogene-DNA repair interaction, to human embryonic and induced pluripotent cells.

Finally, our laboratory is actively investigating the molecular evolution of somatic alterations in lymphoid malignancies. We utilize ultra-deep sequencing of subpopulations sorted from bone marrow specimens to trace the ontogeny of specific alterations identified within lymphomas.


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  • Wu SC, Li LS, Kopp N, Montero J, Chapuy B, Yoda A, Christie AL, Liu H, Christodoulou A, van Bodegom D, van der Zwet J, Layer JV, Tivey T, Lane AA, Ryan JA, Ng SY, DeAngelo DJ, Stone RM, Steensma D, Wadleigh M, Harris M, Mandon E, Ebel N, Andraos R, Romanet V, Dölemeyer A, Sterker D, Zender M, Rodig SJ, Murakami M, Hofmann F, Kuo F, Eck MJ, Silverman LB, Sallan SE, Letai A, Baffert F, Vangrevelinghe E, Radimerski T, Gaul C, Weinstock DM. Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia. Cancer Cell 2015; 28:29-41. PubMed
  • Sujobert P, Poulain L, Paubelle E, Zylbersztejn F, Grenier A, Lambert M, Townsend EC, Brusq JM, Nicodeme E, Decrooqc J, Nepstad I, Green AS, Mondesir J, Hospital MA, Jacque N, Christodoulou A, Desouza TA, Hermine O, Foretz M, Viollet B, Lacombe C, Mayeux P, Weinstock DM, Moura IC, Bouscary D, Tamburini J. Co-activation of AMPK and mTORC1 Induces Cytotoxicity in Acute Myeloid Leukemia. Cell Rep 2015; 11:1446-57. PubMed
  • Weinstock DM, Dalla-Favera R, Gascoyne RD, Leonard JP, Levy R, Lossos IS, Melnick AM, Nowakowski GS, Press OW, Savage KJ, Shipp MA, Staudt LM. A roadmap for discovery and translation in lymphoma. Blood 2015; 125:2175-7. PubMed
  • Yoda A, Adelmant G, Tamburini J, Chapuy B, Shindoh N, Yoda Y, Weigert O, Kopp N, Wu SC, Kim SS, Liu H, Tivey T, Christie AL, Elpek KG, Card J, Gritsman K, Gotlib J, Deininger MW, Makishima H, Turley SJ, Javidi-Sharifi N, Maciejewski JP, Jaiswal S, Ebert BL, Rodig SJ, Tyner JW, Marto JA, Weinstock DM, Lane AA. Mutations in G protein 硫 subunits promote transformation and kinase inhibitor resistance. Nat Med 2015; 21:71-5. PubMed
  • Mansour MR, Reed C, Eisenberg AR, Tseng JC, Twizere JC, Daakour S, Yoda A, Rodig SJ, Tal N, Shochat C, Berezovskaya A, DeAngelo DJ, Sallan SE, Weinstock DM, Izraeli S, Kung AL, Kentsis A, Look AT. Targeting oncogenic interleukin-7 receptor signalling with N-acetylcysteine in T cell acute lymphoblastic leukaemia. British Journal of Haematology 2014. PubMed
  • Shanmugam I, Abbas M, Ayoub F, Mirabal S, Bsaili M, Caulder EK, Weinstock DM, Tomkinson AE, Hromas R, Shaheen M. Ubiquitin Specific Peptidase 20 Regulates Rad17 Stability, Checkpoint Kinase 1 Phosphorylation and DNA Repair by Homologous Recombination. J Biol Chem 2014. PubMed
  • Lane AA, Chapuy B, Lin CY, Tivey T, Li H, Townsend EC, van Bodegom D, Day TA, Wu SC, Liu H, Yoda A, Alexe G, Schinzel AC, Sullivan TJ, Malinge S, Taylor JE, Stegmaier K, Jaffe JD, Bustin M, te Kronnie G, Izraeli S, Harris MH, Stevenson KE, Neuberg D, Silverman LB, Sallan SE, Bradner JE, Hahn WC, Crispino JD, Pellman D, Weinstock DM. Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation. Nat Genet 2014. PubMed
  • Odejide O, Weigert O, Lane AA, Toscano D, Lunning MA, Kopp N, Kim S, van Bodegom D, Bolla S, Schatz JH, Teruya-Feldstein J, Hochberg E, Louissaint A, Dorfman D, Stevenson K, Rodig SJ, Piccaluga PP, Jacobsen E, Pileri SA, Harris NL, Ferrero S, Inghirami G, Horwitz SM, Weinstock DM. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood 2014; 123:1293-6. PubMed
  • Zhong J, Sharma J, Raju R, Palapetta SM, Prasad TS, Huang TC, Yoda A, Tyner JW, van Bodegom D, Weinstock DM, Ziegler SF, Pandey A. TSLP signaling pathway map: a platform for analysis of TSLP-mediated signaling. Database (Oxford) 2014; 2014:bau007. PubMed
  • Park E, Kim JM, Primack B, Weinstock DM, Moreau LA, Parmar K, D'Andrea AD. Inactivation of Uaf1 causes defective homologous recombination and early embryonic lethality in mice. Mol Cell Biol 2013; 33:4360-70. PubMed
  • Wachter F, Grunert M, Blaj C, Weinstock DM, Jeremias I, Ehrhardt H. Impact of the p53 status of tumor cells on extrinsic and intrinsic apoptosis signaling. Cell Commun. Signal 2013; 11:27. PubMed
  • Wray J, Williamson EA, Singh SB, Wu Y, Cogle CR, Weinstock DM, Zhang Y, Lee SH, Zhou D, Shao L, Hauer-Jensen M, Pathak R, Klimek V, Nickoloff JA, Hromas R. PARP1 is required for chromosomal translocations. Blood 2013. PubMed
  • Lane AA, Odejide O, Kopp N, Kim S, Yoda A, Erlich R, Wagle N, Abel GA, Rodig SJ, Antin JH, Weinstock DM. Low frequency clonal mutations recoverable by deep sequencing in patients with aplastic anemia. Leukemia 2013; 27:968-71. PubMed
  • Kluk MJ, Ashworth T, Wang H, Knoechel B, Mason EF, Morgan EA, Dorfman D, Pinkus G, Weigert O, Hornick JL, Chirieac LR, Hirsch M, Oh DJ, South AP, Leigh IM, Pourreyron C, Cassidy AJ, Deangelo DJ, Weinstock DM, Krop IE, Dillon D, Brock JE, Lazar AJ, Peto M, Cho RJ, Stoeck A, Haines BB, Sathayanrayanan S, Rodig S, Aster JC. Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry. PLoS ONE 2013; 8:e67306. PubMed
  • van Bodegom D, Zhong J, Kopp N, Dutta C, Kim MS, Bird L, Weigert O, Tyner J, Pandey A, Yoda A, Weinstock DM. Differences in signaling through the B-cell leukemia oncoprotein CRLF2 in response to TSLP and through mutant JAK2. Blood 2012; 120:2853-63. PubMed
  • Ott CJ, Kopp N, Bird L, Paranal RM, Qi J, Bowman T, Rodig SJ, Kung AL, Bradner JE, Weinstock DM. BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood 2012; 120:2843-52. PubMed
  • Weigert O, Weinstock DM. The evolving contribution of hematopoietic progenitor cells to lymphomagenesis. Blood 2012; 120:2553-61. PubMed
  • Dutta C, Day T, Kopp N, van Bodegom D, Davids MS, Ryan J, Bird L, Kommajosyula N, Weigert O, Yoda A, Fung H, Brown JR, Shapiro GI, Letai A, Weinstock DM. BCL2 suppresses PARP1 function and nonapoptotic cell death. Cancer Res 2012; 72:4193-203. PubMed
  • Weigert O, Kopp N, Lane AA, et al.. Molecular ontogeny of donor-derived follicular lymphoma 2011; 2:47-53.
  • Weigert O, Lane AA, Bird L, Kopp N, Chapuy B, van Bodegom D, Toms AV, Marubayashi S, Christie AL, McKeown M, Paranal RM, Bradner JE, Yoda A, Gaul C, Vangrevelinghe E, Romanet V, Murakami M, Tiedt R, Ebel N, Evrot E, De Pover A, Régnier CH, Erdmann D, Hofmann F, Eck MJ, Sallan SE, Levine RL, Kung AL, Baffert F, Radimerski T, Weinstock DM. Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition. J Exp Med 2012. PubMed
  • Shindoh N, Yoda A, Yoda Y, Sullivan TJ, Weigert O, Lane AA, Kopp N, Bird L, Rodig SJ, Fox EA, Weinstock DM. Next-generation cDNA screening for oncogene and resistance phenotypes. PLoS ONE 2012; 7:e49201. PubMed
  • DiCarlo AL, Maher C, Hick JL, Hanfling D, Dainiak N, Chao N, Bader JL, Coleman CN, Weinstock DM. Radiation injury after a nuclear detonation: medical consequences and the need for scarce resources allocation. Disaster Med Public Health Prep 2011; 5 Suppl 1:S32-44. PubMed
  • Moskwa P, Buffa FM, Pan Y, Panchakshari R, Gottipati P, Muschel RJ, Beech J, Kulshrestha R, Abdelmohsen K, Weinstock DM, Gorospe M, Harris AL, Helleday T, Chowdhury D. miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Mol Cell 2011; 41:210-20. PubMed
  • Fung H, Weinstock DM. Repair at single targeted DNA double-strand breaks in pluripotent and differentiated human cells. PLoS ONE 2011; 6:e20514. PubMed
  • Xu Y, Sun Y, Jiang X, Ayrapetov MK, Moskwa P, Yang S, Weinstock DM, Price BD. The p400 ATPase regulates nucleosome stability and chromatin ubiquitination during DNA repair. J Cell Biol 2010; 191:31-43. PubMed
  • Tsai AG, Yoda A, Weinstock DM, Lieber MR. t(X;14)(p22;q32)/t(Y;14)(p11;q32) CRLF2-IGH translocations from human B-lineage ALLs involve CpG-type breaks at CRLF2, but CRLF2/P2RY8 intrachromosomal deletions do not. Blood 2010; 116:1993-4. PubMed
  • Wray J, Williamson EA, Chester S, Farrington J, Sterk R, Weinstock DM, Jasin M, Lee SH, Nickoloff JA, Hromas R. The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations. Cancer Genet Cytogenet 2010; 200:184-90. PubMed
  • Davids MS, Case C, Confer DL, Weisdorf DJ, Weinstock DM. Medical management of radiation victims in the United States. Health Phys 2010; 98:833-7. PubMed
  • Yoda A, Yoda Y, Chiaretti S, Bar-Natan M, Mani K, Rodig SJ, West N, Xiao Y, Brown JR, Mitsiades C, Sattler M, Kutok JL, DeAngelo DJ, Wadleigh M, Piciocchi A, Dal Cin P, Bradner JE, Griffin JD, Anderson KC, Stone RM, Ritz J, Foà R, Aster JC, Frank DA, Weinstock DM. Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 2010; 107:252-7. PubMed
  • Weinstock DM. Epstein-Barr virus, lymphoma risk and the potential role of HIV infection in IBD patients undergoing immunosuppression. Dig Dis 2010; 28:519-24. PubMed
  • Fernandes MS, Reddy MM, Gonneville JR, DeRoo SC, Podar K, Griffin JD, Weinstock DM, Sattler M. BCR-ABL promotes the frequency of mutagenic single-strand annealing DNA repair. Blood 2009; 114:1813-9. PubMed
  • Brunet E, Simsek D, Tomishima M, DeKelver R, Choi VM, Gregory P, Urnov F, Weinstock DM, Jasin M. Chromosomal translocations induced at specified loci in human stem cells. Proc Natl Acad Sci U S A 2009; 106:10620-5. PubMed
  • Kim JM,Parmar K,Huang M,Weinstock DM,Ruit CA,Kutok JL,D'Andrea AD. Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotype. Dev Cell 2009; 16:314-20. PubMed
  • Chowdhury D, Xu X, Zhong X, Ahmed F, Zhong J, Liao J, Dykxhoorn DM, Weinstock DM, Pfeifer GP, Lieberman J. A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replication. Mol Cell 2008; 31:33-46. PubMed
  • Weinstock DM, Case C Jr, Bader JL, Chao NJ, Coleman CN, Hatchett RJ, Weisdorf DJ, Confer DL. Radiological and nuclear events: contingency planning for hematologist/oncologists. Blood 2008; 111:5440-5. PubMed
  • Weinstock DM, Brunet E, Jasin M. Induction of chromosomal translocations in mouse and human cells using site-specific endonucleases. J Natl Cancer Inst Monogr 2008. PubMed
  • Perales MA, Ishill N, Lomazow WA, Weinstock DM, Papadopoulos EB, Dastigir H, Chiu M, Boulad F, Castro-Malaspina HR, Heller G, Jakubowski AA, O'Reilly RJ, Small TN, Young JW, Kernan NA. Long-term follow-up of patients treated with daclizumab for steroid-refractory acute graft-vs-host disease. Bone Marrow Transplant 2007; 40:481-6. PubMed
  • Weinstock DM, Brunet E, Jasin M. Formation of NHEJ-derived reciprocal chromosomal translocations does not require Ku70. Nat Cell Biol 2007; 9:978-81. PubMed
  • Weinstock DM, Richardson CA, Elliott B, Jasin M. Modeling oncogenic translocations: distinct roles for double-strand break repair pathways in translocation formation in mammalian cells. DNA Repair (Amst) 2006; 5:1065-74. PubMed
  • Weinstock DM, Ambrossi GG, Brennan C, Kiehn TE, Jakubowski A. Preemptive diagnosis and treatment of Epstein-Barr virus-associated post transplant lymphoproliferative disorder after hematopoietic stem cell transplant: an approach in development. Bone Marrow Transplant 2006; 37:539-46. PubMed
  • Weinstock DM, Zuccotti G. Adamantane resistance in influenza A. JAMA 2006; 295:934-6. PubMed
  • Weinstock DM, Elliott B, Jasin M. A model of oncogenic rearrangements: differences between chromosomal translocation mechanisms and simple double-strand break repair. Blood 2005; 107:777-80. PubMed
  • Weinstock DM, Nakanishi K, Helgadottir HR, Jasin M. Assaying double-strand break repair pathway choice in mammalian cells using a targeted endonuclease or the RAG recombinase. Methods Enzymol 2006; 409:524-40. PubMed
  • Weinstock DM, Jasin M. Alternative pathways for the repair of RAG-induced DNA breaks. Mol Cell Biol 2005; 26:131-9. PubMed
  • Weinstock DM, Gubareva LV, Zuccotti G. Prolonged shedding of multidrug-resistant influenza A virus in an immunocompromised patient. N Engl J Med 2003; 348:867-8. PubMed