Photo of James D. Griffin,  MD

James D. Griffin, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3360
Fax: (617) 632-2260

James D. Griffin, MD

Dana-Farber Cancer Institute


  • Professor, Medicine, Harvard Medical School
  • Chair, Medical Oncology, Dana-Farber Cancer Institute
  • Director, Medical Oncology, Brigham And Women's Hospital



  • Member, Clinical Science Coordinating Committee
  • Member, Center Scientific Council
  • Deputy Associate Director, Clinical Science, Executive Committee

Research Abstract

Dr. Griffin's laboratory is focused on understanding the genetic events that cause leukemia. The major laboratory interests can be divided into three broad areas: 1. Mechanisms of transformation by the BCR/ABL oncogene. The product of the BCR/ABL oncogene is an activated tyrosine kinase which induces a myeloproliferative syndrome in humans and mice. p210BCR/ABL transforms hematopoietic cells at least in part by constitutively activating signal transduction pathways which are normally tightly regulated by growth factors such as IL-3 or GM-CSF, such as those involved in blocking apoptosis. Several critical targets of BCR/ABL have been identified, including CRKL, SHP2, PI3K, SHIP, and RAS. Defining the individual contribution of each pathway to CML is underway, as are gene discovery approaches to identifying novel targets. 2. Mechanisms of transformation by the FLT3 oncogene and development of targeted therapies against FLT3. FLT3 is mutated in about 35% of all cases of AML. The lab has developed a small molecule tyrosine kinase inhibitor that blocks signaling from FLT3, which is currently being tested in clinical trials. In vitro studies of mechanism and murine models are being used to develop the next generation of AML therapies using this inhibitor as part of the therapy. 3.Signaling of the Notch receptor in hematopoietic and epithelial cells. We have recently cloned a several nes members of the Notch signaling pathway, a family of transcriptional regulators (mastermind-like genes) that modulates expression of Notch regulated genes in a variety of cell lineages. One family member, MAML2, has recently been shown to be mutated in mucoepidermoid cancer and appears to be the cause of that neoplasm.


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  • Nonami A, Sattler M, Weisberg E, Liu Q, Zhang J, Patricelli MP, Christie AL, Saur AM, Kohl NE, Kung AL, Yoon H, Sim T, Gray NS, Griffin JD. Identification of novel therapeutic targets in acute leukemias with NRAS mutations using a pharmacological approach. Blood 2015. PubMed
  • Weisberg E, Nonami A, Griffin JD. Combination therapy with nilotinib for drug-sensitive and drug-resistant BCR-ABL-positive leukemia and other malignancies. Arch. Toxicol. 2014. PubMed
  • Weisberg E, Nonami A, Chen Z, Nelson E, Chen Y, Liu F, Cho H, Zhang J, Sattler M, Mitsiades C, Wong KK, Liu Q, Gray NS, Griffin JD. Upregulation of IGF1R by Mutant RAS in Leukemia and Potentiation of RAS Signaling Inhibitors by Small-Molecule Inhibition of IGF1R. Clin Cancer Res 2014. PubMed
  • Wu H, Wang W, Liu F, Weisberg EL, Tian B, Chen Y, Li B, Wang A, Wang B, Zhao Z, McMillin DW, Hu C, Li H, Wang J, Liang Y, Buhrlage SJ, Liang J, Liu J, Yang G, Brown JR, Treon SP, Mitsiades CS, Griffin JD, Liu Q, Gray NS. Discovery of a potent, covalent BTK inhibitor for B-cell lymphoma. ACS Chem Biol 2014. PubMed
  • Adamia S, Bar-Natan M, Haibe-Kains B, Pilarski PM, Bach C, Pevzner S, Calimeri T, Avet-Loiseau H, Lode L, Verselis S, Fox EA, Galinsky I, Mathews S, Dagogo-Jack I, Wadleigh M, Steensma DP, Motyckova G, Deangelo DJ, Quackenbush J, Tenen DG, Stone RM, Griffin JD. NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute myeloid leukemia (AML): new potential targets in AML. Blood 2014. PubMed
  • Adamia S, Haibe-Kains B, Pilarski PM, Bar-Natan M, Pevzner S, Avet-Loiseau H, Lode L, Verselis S, Fox EA, Burke J, Galinsky I, Dagogo-Jack I, Wadleigh M, Steensma DP, Motyckova G, Deangelo DJ, Quackenbush J, Stone R, Griffin JD. A genome-wide aberrant RNA splicing in patients with acute myeloid leukemia identifies novel potential disease markers and therapeutic targets. Clin Cancer Res 2014; 20:1135-45. PubMed
  • Kim HG, Tan L, Weisberg EL, Liu F, Canning P, Choi HG, Ezell SA, Wu H, Zhao Z, Wang J, Mandinova A, Griffin JD, Bullock AN, Liu Q, Lee SW, Gray NS. Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor. ACS Chem Biol 2013; 8:2145-50. PubMed
  • Toms AV, Deshpande A, McNally R, Jeong Y, Rogers JM, Kim CU, Gruner SM, Ficarro SB, Marto JA, Sattler M, Griffin JD, Eck MJ. Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases. Nat Struct Mol Biol 2013; 20:1221-3. PubMed
  • Adamia S, Pilarski PM, Bar-Natan M, Stone RM, Griffin JD. Alternative splicing in chronic myeloid leukemia (CML): a novel therapeutic target? Curr Cancer Drug Targets 2013; 13:735-48. PubMed
  • Liu F, Zhang X, Weisberg E, Chen S, Hur W, Wu H, Zhao Z, Wang W, Mao M, Cai C, Simon NI, Sanda T, Wang J, Look AT, Griffin JD, Balk SP, Liu Q, Gray NS. Discovery of a Selective Irreversible BMX Inhibitor for Prostate Cancer. ACS Chem Biol 2013. PubMed
  • Griffin JD, Guerin A, Chen L, Macalalad AR, Luo J, Ionescu-Ittu R, Wu EQ. Comparing nilotinib with dasatinib as second-line therapies in patients with chronic myelogenous leukemia resistant or intolerant to imatinib - a retrospective chart review analysis. Curr Med Res Opin 2013. PubMed
  • Weisberg E, Liu Q, Zhang X, Nelson E, Sattler M, Liu F, Nicolais M, Zhang J, Mitsiades C, Smith RW, Stone R, Galinsky I, Nonami A, Griffin JD, Gray N. Selective Akt inhibitors synergize with tyrosine kinase inhibitors and effectively override stroma-associated cytoprotection of mutant FLT3-positive AML cells. PLoS ONE 2013; 8:e56473. PubMed
  • Choi HG, Zhang J, Weisberg E, Griffin JD, Sim T, Gray NS. Development of 'DFG-out' inhibitors of gatekeeper mutant kinases. Bioorg Med Chem Lett 2012; 22:5297-302. PubMed
  • Deng X, Zhou W, Weisberg E, Wang J, Zhang J, Sasaki T, Nelson E, Griffin JD, Jänne PA, Gray NS. An amino-indazole scaffold with spectrum selective kinase inhibition of FLT3, PDGFR留 and kit. Bioorg Med Chem Lett 2012; 22:4579-84. PubMed
  • Guérin A, Chen L, Wu EQ, Ponce de Leon D, Griffin JD. A retrospective analysis of therapy adherence in imatinib resistant or intolerant patients with chronic myeloid leukemia receiving nilotinib or dasatinib in a real-world setting. Curr Med Res Opin 2012; 28:1155-62. PubMed
  • Nelson EA, Walker SR, Xiang M, Weisberg E, Bar-Natan M, Barrett R, Liu S, Kharbanda S, Christie AL, Nicolais M, Griffin JD, Stone RM, Kung AL, Frank DA. The STAT5 Inhibitor Pimozide Displays Efficacy in Models of Acute Myelogenous Leukemia Driven by FLT3 Mutations. Genes Cancer 2012; 3:503-11. PubMed
  • Weisberg E, Azab AK, Manley PW, Kung AL, Christie AL, Bronson R, Ghobrial IM, Griffin JD. Inhibition of CXCR4 in CML cells disrupts their interaction with the bone marrow microenvironment and sensitizes them to nilotinib. Leukemia 2012; 26:985-90. PubMed
  • Weisberg E, Liu Q, Nelson E, Kung AL, Christie AL, Bronson R, Sattler M, Sanda T, Zhao Z, Hur W, Mitsiades C, Smith R, Daley JF, Stone R, Galinsky I, Griffin JD, Gray N. Using combination therapy to override stromal-mediated chemoresistance in mutant FLT3-positive AML: synergism between FLT3 inhibitors, dasatinib/multi-targeted inhibitors, and JAK inhibitors. Leukemia 2012. PubMed
  • Deshpande A, Reddy MM, Schade GO, Ray A, Chowdary TK, Griffin JD, Sattler M. Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms. Leukemia 2012; 26:708-15. PubMed
  • Reddy MM, Fernandes MS, Deshpande A, Weisberg E, Inguilizian HV, Abdel-Wahab O, Kung AL, Levine RL, Griffin JD, Sattler M. The JAK2V617F oncogene requires expression of inducible phosphofructokinase/fructose-bisphosphatase 3 for cell growth and increased metabolic activity. Leukemia 2012; 26:481-9. PubMed
  • Nelson EA, Walker SR, Weisberg E, Bar-Natan M, Barrett R, Gashin LB, Terrell S, Klitgaard JL, Santo L, Addorio MR, Ebert BL, Griffin JD, Frank DA. The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood 2011; 117:3421-9. PubMed
  • Weisberg E, Ray A, Nelson E, Adamia S, Barrett R, Sattler M, Zhang C, Daley JF, Frank D, Fox E, Griffin JD. Reversible Resistance Induced by FLT3 Inhibition: A Novel Resistance Mechanism in Mutant FLT3-Expressing Cells. PLoS ONE 2011; 6:e25351. PubMed
  • Wu EQ, Guerin A, Yu AP, Bollu VK, Guo A, Griffin JD. Retrospective real-world comparison of medical visits, costs, and adherence between nilotinib and dasatinib in chronic myeloid leukemia. Curr Med Res Opin 2010; 26:2861-9. PubMed
  • Fernandes MS, Reddy MM, Croteau NJ, Walz C, Weisbach H, Podar K, Band H, Carroll M, Reiter A, Larson RA, Salgia R, Griffin JD, Sattler M. Novel oncogenic mutations of CBL in human acute myeloid leukemia that activate growth and survival pathways depend on increased metabolism. J Biol Chem 2010; 285:32596-605. PubMed
  • Weisberg E, Choi HG, Barrett R, Zhou W, Zhang J, Ray A, Nelson EA, Jiang J, Moreno D, Stone R, Galinsky I, Fox E, Adamia S, Kung AL, Gray NS, Griffin JD. Discovery and characterization of novel mutant FLT3 kinase inhibitors. Mol Cancer Ther 2010; 9:2468-77. PubMed
  • Chen J, Kesari S, Rooney C, Strack PR, Chen J, Shen H, Wu L, Griffin JD. Inhibition of Notch Signaling Blocks Growth of Glioblastoma Cell Lines and Tumor Neurospheres. Genes Cancer 2010; 1:822-835. PubMed
  • Weisberg E, Choi HG, Ray A, Barrett R, Zhang J, Sim T, Zhou W, Seeliger M, Cameron M, Azam M, Fletcher JA, Debiec-Rychter M, Mayeda M, Moreno D, Kung AL, Janne PA, Khosravi-Far R, Melo JV, Manley P, Adamia S, Wu C, Gray N, Griffin JD. Discovery of a small molecule type II inhibitor of wild-type and gatekeeper mutants of BCR-ABL, PDGFR{alpha}, Kit, and Src kinases. Blood 2010; 115:4206-16. PubMed
  • Jin B, Shen H, Lin S, Li JL, Chen Z, Griffin JD, Wu L. The maml1 co-activator regulates constitutive NF-{kappa}B signaling and cell survival. J Biol Chem 2010; 285:14356-65. PubMed
  • Zhang Y, Askenazi M, Jiang J, Luckey CJ, Griffin JD, Marto JA. A robust error model for iTRAQ quantification reveals divergent signaling between oncogenic FLT3 mutants in acute myeloid leukemia. Mol Cell Proteomics 2010; 9:780-90. PubMed
  • McMillin DW, Delmore J, Weisberg E, Negri JM, Geer DC, Klippel S, Mitsiades N, Schlossman RL, Munshi NC, Kung AL, Griffin JD, Richardson PG, Anderson KC, Mitsiades CS. Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity. Nat Med 2010; 16:483-9. 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
  • Sattler M, Griffin JD. JAK2 gets histone H3 rolling. Cancer Cell 2009; 16:365-6. 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
  • Weisberg E,Barrett R,Liu Q,Stone R,Gray N,Griffin JD. FLT3 inhibition and mechanisms of drug resistance in mutant FLT3-positive AML. Drug Resist Updat 2009; 12:81-9. PubMed
  • Weisberg E,Roesel J,Bold G,Furet P,Jiang J,Cools J,Wright RD,Nelson E,Barrett R,Ray A,Moreno D,Hall-Meyers E,Stone R,Galinsky I,Fox E,Gilliland G,Daley JF,Lazo-Kallanian S,Kung AL,Griffin JD. Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cells. Blood 2008; 112:5161-70. PubMed
  • Smith KA,Griffin JD. Following the cytokine signaling pathway to leukemogenesis: a chronology. J Clin Invest 2008; 118:3564-73. PubMed
  • Weisberg E, Wright RD, McMillin DW, Mitsiades C, Ray A, Barrett R, Adamia S, Stone R, Galinsky I, Kung AL, Griffin JD. Stromal-mediated protection of tyrosine kinase inhibitor-treated BCR-ABL-expressing leukemia cells. Mol Cancer Ther 2008; 7:1121-9. PubMed
  • Loriaux MM, Levine RL, Tyner JW, Frohling S, Scholl C, Stoffregen EP, Wernig G, Erickson H, Eide CA, Berger R, Bernard OA, Griffin JD, Stone RM, Lee B, Meyerson M, Heinrich MC, Deininger MW, Gilliland DG, Druker BJ. High-throughput sequence analysis of the tyrosine kinome in acute myeloid leukemia. Blood 2008; 111:4788-96. PubMed
  • Wernig G, Gonneville JR, Crowley BJ, Rodrigues MS, Reddy MM, Hudon HE, Walz C, Reiter A, Podar K, Royer Y, Constantinescu SN, Tomasson MH, Griffin JD, Gilliland DG, Sattler M. The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes. Blood 2008; 111:3751-9. PubMed
  • Weisberg E, Banerji L, Wright RD, Barrett R, Ray A, Moreno D, Catley L, Jiang J, Hall-Meyers E, Sauveur-Michel M, Stone R, Galinsky I, Fox E, Kung AL, Griffin JD. Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells. Blood 2008; 111:3723-34. PubMed
  • Frohling S, Scholl C, Levine RL, Loriaux M, Boggon TJ, Bernard OA, Berger R, Dohner H, Dohner K, Ebert BL, Teckie S, Golub TR, Jiang J, Schittenhelm MM, Lee BH, Griffin JD, Stone RM, Heinrich MC, Deininger MW, Druker BJ, Gilliland DG. Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles. Cancer Cell 2007; 12:501-13. PubMed
  • Griffin JE. Resuscitation decisions: yes, but who is in charge? BMJ 2007; 335:1008. PubMed
  • Wu L, Maillard I, Nakamura M, Pear WS, Griffin JD. The transcriptional coactivator Maml1 is required for Notch2-mediated marginal zone B-cell development. Blood 2007; 110:3618-23. PubMed
  • Weisberg E, Kung AL, Wright RD, Moreno D, Catley L, Ray A, Zawel L, Tran M, Cools J, Gilliland G, Mitsiades C, McMillin DW, Jiang J, Hall-Meyers E, Griffin JD. Potentiation of antileukemic therapies by Smac mimetic, LBW242: effects on mutant FLT3-expressing cells. Mol Cancer Ther 2007; 6:1951-61. PubMed
  • Ray A, Cowan-Jacob SW, Manley PW, Mestan J, Griffin JD. Identification of BCR-ABL point mutations conferring resistance to the Abl kinase inhibitor AMN107 (nilotinib) by a random mutagenesis study. Blood 2007; 109:5011-5. PubMed
  • Weisberg E, Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid leukaemia. Nat Rev Cancer 2007; 7:345-56. PubMed
  • Zhang H, Bajraszewski N, Wu E, Wang H, Moseman AP, Dabora SL, Griffin JD, Kwiatkowski DJ. PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. J Clin Invest 2007; 117:730-8. PubMed
  • Weisberg E, Catley L, Wright RD, Moreno D, Banerji L, Ray A, Manley PW, Mestan J, Fabbro D, Jiang J, Hall-Meyers E, Callahan L, DellaGatta JL, Kung AL, Griffin JD. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias. Blood 2006; 109:2112-20. PubMed
  • Chen J, Jette C, Kanki JP, Aster JC, Look AT, Griffin JD. NOTCH1-induced T-cell leukemia in transgenic zebrafish. Leukemia 2007; 21:462-71. PubMed
  • Weisberg E, Wright RD, Jiang J, Ray A, Moreno D, Manley PW, Fabbro D, Hall-Meyers E, Catley L, Podar K, Kung AL, Griffin JD. Effects of PKC412, nilotinib, and imatinib against GIST-associated PDGFRA mutants with differential imatinib sensitivity. Gastroenterology 2006; 131:1734-42. PubMed
  • Walz C, Crowley BJ, Hudon HE, Gramlich JL, Neuberg DS, Podar K, Griffin JD, Sattler M. Activated Jak2 with the V617F point mutation promotes G1/S phase transition. J Biol Chem 2006; 281:18177-83. PubMed
  • Weisberg E, Manley P, Mestan J, Cowan-Jacob S, Ray A, Griffin JD. AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. Br J Cancer 2006; 94:1765-9. PubMed
  • Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B, Tanaka C, Manley P, Rae P, Mietlowski W, Bochinski K, Hochhaus A, Griffin JD, Hoelzer D, Albitar M, Dugan M, Cortes J, Alland L, Ottmann OG. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006; 354:2542-51. PubMed
  • Shen H, McElhinny AS, Cao Y, Gao P, Liu J, Bronson R, Griffin JD, Wu L. The Notch coactivator, MAML1, functions as a novel coactivator for MEF2C-mediated transcription and is required for normal myogenesis. Genes Dev 2006; 20:675-88. PubMed
  • Sattler M, Walz C, Crowley BJ, Lengfelder E, J. A sensitive high-throughput method to detect activating mutations of Jak2 in peripheral-blood samples. Blood 2006; 107:1237-8. PubMed
  • Jiang J, Greulich H, J. Epidermal growth factor-independent transformation of Ba/F3 cells with cancer-derived epidermal growth factor receptor mutants induces gefitinib-sensitive cell cycle progression. Cancer Res 2005; 65:8968-74. PubMed
  • Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, Boggon TJ, Wlodarska I, Clark JJ, Moore S, Adelsperger J, Koo S, Lee JC, Gabriel S, Mercher T, D'Andrea A, Frohling S, Dohner K, Marynen P, Vandenberghe P, Mesa RA, Tefferi A, Griffin JD, Eck MJ, Sellers WR, Meyerson M, Golub TR, Lee SJ, Gilliland DG. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005; 7:387-97. PubMed