James Griffin
EDUCATIONAL TITLES
DF/HCC PROGRAM AFFILIATION
DF/HCC ASSOCIATIONS
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.
Publications
- Hatcher JM, Weisberg E, Sim T, Stone RM, Liu S, Griffin JD, Gray NS. Discovery of a Highly Potent and Selective Indenoindolone Type 1 Pan-FLT3 Inhibitor. 2016; 7:476-81. PubMed
- Liu X, Wang A, Liang X, Chen C, Liu J, Zhao Z, Wu H, Deng Y, Wang L, Wang B, Wu J, Liu F, Fernandes SM, Adamia S, Stone RM, Galinsky IA, Brown JR, Griffin JD, Zhang S, Loh T, Zhang X, Wang W, Weisberg EL, Liu J, Liu Q. Characterization of selective and potent PI3Kδ inhibitor (PI3KDIN- 015) for B-Cell malignances. 2016. PubMed
- Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, Stevenson KE, Rao P, Vadhi R, Andreeff M, Armand P, Ballen KK, Barzaghi-Rinaudo P, Cahill S, Clark RA, Cooke VG, Davids MS, DeAngelo DJ, Dorfman DM, Eaton H, Ebert BL, Etchin J, Firestone B, Fisher DC, Freedman AS, Galinsky IA, Gao H, Garcia JS, Garnache-Ottou F, Graubert TA, Gutierrez A, Halilovic E, Harris MH, Herbert ZT, Horwitz SM, Inghirami G, Intlekoffer AM, Ito M, Izraeli S, Jacobsen ED, Jacobson CA, Jeay S, Jeremias I, Kelliher MA, Koch R, Konopleva M, Kopp N, Kornblau SM, Kung AL, Kupper TS, LaBoeuf N, LaCasce AS, Lees E, Li LS, Look AT, Murakami M, Muschen M, Neuberg D, Ng SY, Odejide OO, Orkin SH, Paquette RR, Place AE, Roderick JE, Ryan JA, Sallan SE, Shoji B, Silverman LB, Soiffer RJ, Steensma DP, Stegmaier K, Stone RM, Tamburini J, Thorner AR, van Hummelen P, Wadleigh M, Wiesmann M, Weng AP, Wuerthner JU, Williams DA, Wollison BM, Lane AA, Letai A, Bertagnolli MM, Ritz J, Brown M, Long H, Aster JC, Shipp MA, Griffin JD, Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell 2016; 29:574-86. PubMed
- Wang A, Wu H, Chen C, Hu C, Qi Z, Wang W, Yu K, Liu X, Zou F, Zhao Z, Wu J, Liu J, Liu F, Wang L, Stone RM, Galinksy IA, Griffin JD, Zhang S, Weisberg EL, Liu J, Liu Q. Dual Inhibition of AKT/FLT3-ITD by A674563 Overcomes FLT3 Ligand-Induced Drug Resistance in FLT3-ITD positive AML. 2016. PubMed
- Weisberg E, Halilovic E, Cooke VG, Nonami A, Ren T, Sanda T, Simkin I, Yuan J, Antonakos B, Barys L, Ito M, Stone R, Galinsky I, Cowens K, Nelson E, Sattler M, Jeay S, Wuerthner JU, McDonough SM, Wiesmann M, Griffin JD. Inhibition of Wild-Type p53-Expressing AML by the Novel Small Molecule HDM2 Inhibitor CGM097. Mol Cancer Ther 2015; 14:2249-59. PubMed
- de la Puente P, Weisberg E, Muz B, Nonami A, Luderer M, Stone RM, Melo JV, Griffin JD, Azab AK. Identification of ILK as a novel therapeutic target for acute and chronic myeloid leukemia. Leuk Res 2015. PubMed
- 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 pharmacologic approach. Blood 2015. PubMed
- Chen J, Li JL, Chen Z, Griffin JD, Wu L. Gene expression profiling analysis of CRTC1-MAML2 fusion oncogene-induced transcriptional program in human mucoepidermoid carcinoma cells. BMC Cancer 2015; 15:803. 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
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