• Researcher Profile

    James D. Griffin, MD

    James D. Griffin, MD
    Chair, Medical Oncology
    Senior Physician

    Professor of Medicine, Harvard Medical School


    Hematologic Oncology

    Office phone: 617-632-3360
    Fax: 617-632-2260
    Email: james_griffin@dfci.harvard.edu

    Preferred contact method: office phone

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    Research Department

    Medical Oncology/Hematologic Neoplasia


    Leukemia, Myelodysplasia

    Area of Research

    Mechanisms of Transformation in Leukemia

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Dana D1608
    Boston, MA 02215


    Dr. Griffin received his MD from Harvard Medical School in 1974. After residency training in internal medicine at Johns Hopkins Hospital, he completed a hematology fellowship at Massachusetts General Hospital and a medical oncology fellowship at DFCI. In 1981, he joined the staff of DFCI, where he is now director of the Leukemia Program and chair of the Department of Medical Oncology. He also serves on the scientific advisory boards of the Lombardi Cancer Center at Georgetown University and the Johns Hopkins Cancer Center.

    Recent Awards

    • Johns Hopkins University Society of Scholars, 2003
    • Dr. Anthony Cortese Award, 2001


    Mechanisms of Transformation in Leukemia

    There are several major projects in our laboratory. The first involves trying to understand how tyrosine kinase oncogenes cause certain types of chronic leukemia. The prototypic tyrosine kinase oncogene, BCR-ABL, causes human chronic myeloid leukemia and rapidly transforms hematopoietic cells in mice. BCR-ABL encodes an activated tyrosine kinase that is localized to the cytoplasm and cytoskeleton. In addition, mutations of the tyrosine kinase oncogene FLT3 have been detected in about 30% of patients with acute myelogenous leukemia and a small number of patients with acute lvmphocytic leukemia or myelodysplastic syndrome. Recently, mutations in the JAK2 tyrosine kinase oncogene have been shown to cause polycythemia vera and some other myeloproliferative diseases.
    Each of these mutations results in constitutive activation of the kinase and unregulated signals causing growth, blocking differentiation, and enhancing viability. We are interested in defining the signaling pathways leading to these biological effects, since many of these pathways constitute potential targets for drug development. Over the last few years, we have participated in the development of novel small-molecule inhibitors for BCR-ABL (AMN107) and FLT3 (PKC412), both of which are currently in clinical trials; we are also working actively to develop inhibitors of JAK2.
    The second major project is in signal transduction of Notch receptors. Notch is a highly conserved signaling pathway that regulates development of many tissues, and in hematopoiesis Notch is likely to play a role in the differentiation of T cells and B cells. We have cloned new components in the Notch signaling pathway, and a number of studies are ongoing with regard to these new nuclear proteins. One member of this family of proteins, called MAML2, has now been shown to be involved in a recurrent chromosomal translocation, t(11;19), in most cases of mucoepidermoid cancer, and appears to cause that disease.
    Our laboratory also is involved in projects related to the development of novel therapies for hematologic malignancies, involving immunotherapy, gene therapy, and chemotherapy.

    Select Publications

    • Wu L, Liu J, Gao P, Nakamura M, Cao Y, Shen H, Griffin JD. Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation. EMBO J 2005;24:2391-402
    • 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.
    • Weisberg E, Manley PW, Breitenstein W, Brüggen J, Cowan-Jacob SW, Huntly B, Fabbro D, Fendrich G, Hall-Meyers E, Kung AL, Mestan J, Daley GQ, Callahan L, Catley L, Cavazza C, Mohammed A, Ray A, Neuberg D, Wright RD, Gilliland DG, Griffin JD. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 2005;7:129-41.
    • Stone RM, Deangelo DJ, Klimek V, Galinsky I, Estey E, Nimer SD, Grandin W, Lebwohl D, Wang Y, Cohen P, Fox EA, Neuberg D, Clark J, Gilliland DG, Griffin JD. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood 2005;105:54-60
    • Frhling S, Scholl C, Levine RL, Loriaux M, Boggon TJ, Bernard OA, Berger R, Dhner H, Dhner 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
    • Chen J, Imanaka N, Chen J, Griffin JD. Hypoxia potentiates Notch signaling in breast cancer leading to decreased E-cadherin expression and increased cell migration and invasion. Br J Cancer. 2010 Jan 19;102(2):351-60.


    • Sattler, Martin, PhD
    • Weisberg, Ellen, PhD
    • Wu, Lizi, PhD
    • Scheijen, Blanca, PhD


    • Jiang, Jingrui, PhD
    • Nakamura, Makoto, MD
    • Ray, Arghya, PhD
    • Chen, Jihua, PhD
    • Chen, Jie Jenny, Ph.D.
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