个人简介

Ph.D., University of Ottawa (1998); Post-Doctoral Fellowship, University of California San Francisco (1998-2002)

研究领域

Our research focus is on a cytokine, interleukin-7 (IL-7), that is an essential growth factor for lymphocytes. Defects in IL-7 or its deregulation cause immunodeficiency and lymphomas respectively. Our long-term goal is to use genetic models of IL-7 function to understand the key intracellular, signaling processes that contribute to these diseases and to formulate novel therapeutic strategies. The projects that we are pursuing include: 1. Genetic analysis of the role of proliferation and survival signals in lymphocyte development, maintenance and lymphomagenesis using transgenic and knock-in mouse models, and cell culture-based approaches. 2. Determination of the dose-sensitivity of IL-7-induced survival factors (STAT5, phosphatidylinositol-3 kinase, Akt) by haploinsufficiency analysis. 3. IL-7 regulation of CD8 SP T-cell development and homeostasis. 4. Functional genomic, proteomic and gene array approaches to identify novel effectors induced by IL-7 with significant roles in lymphoid development and lymphomagenesis.

The development, maintenance and proper functioning of T- and B-cells are essential for the survival of mammals in a pathogen-ridden environment. Their absence results in inherited or acquired immunodeficiency, the latter of which is the basis of a growing health crisis. Conversely, deregulated growth and development can lead to cancer of the immune system. Leukemia and Lymphoma are the most common cancers among children. Our research focus is on a cytokine, interleukin-7 (IL-7), that is an essential growth factor for lymphocytes. Defects in IL-7 or its deregulation cause immunodeficiency and lymphomas respectively. Our long-term goal is to use genetic models of IL-7 function to understand the key intracellular, signaling processes that contribute to these diseases and to formulate novel therapeutic strategies. The projects that we are pursuing include: 1. Genetic analysis of the role of proliferation and survival signals in lymphocyte development, maintenance and lymphomagenesis using transgenic and knock-in mouse models, and cell culture-based approaches. 2. Determination of the dose-sensitivity of IL-7-induced survival factors (STAT5, phosphatidylinositol-3 kinase, Akt) by haploinsufficiency analysis. 3. IL-7 regulation of CD8 SP T-cell development and homeostasis. 4. Functional genomic, proteomic and gene array approaches to identify novel effectors induced by IL-7 with significant roles in lymphoid development and lymphomagenesis.

近期论文

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Osborne, L., Dhanji, S., Snow, J.W., Priatel, J., Ma, M.C., M. Jill Miners, Teh, H-S., Goldsmith, M.A and Abraham, N. 2007. Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice. J Exp Med 204: 619-631 Abraham, N., Ma, M.C., Snow, J.W., Miners, M.J., Herndier, B.G. and Goldsmith, M.A. 2005. Haploinsufficiency identifies STAT5 as a modifier of IL-7 induced lymphomas. Oncogene Epub 2005 May 2 Snow, J.W., Abraham, N., Ma, M.C., Bronson S. K., and Goldsmith, M.A. 2003. Transgenic Bcl-2 is Not Sufficient to Rescue All Hematolymphoid Defects in STAT5A/5B-deficient Mice. Exp Hematol 31: 1253-1258 Snow, J.W., Abraham, N., Ma, M.C., Abbey, N.W., Herndier, B. and Goldsmith, M.A. 2001. STAT5 promotes multilineage hematolymphoid development in Vivo through effects on early hematopoietic progenitor cells. Blood 99(1):95-101 Stojdl, D.F., Abraham, N., Knowles, S., Marius, R., Brasey, A., Lichty, B.D., Brown, E.G., Sonenberg, N. and Bell, J.C. 2000. The murine double-stranded RNA-dependent protein kinase PKR is required for resistance to vesicular stomatitis virus. J Virol 74(20):9580-5 Abraham, N., Stojdl, D.F., Duncan, P.I., Méthot, N., Ishii, T., Dubé, M., Vanderhyden, B.C., Atkins, H.L., Gray, D.A., McBurney, M.W., Koromilas, A.E., Brown, E.G., Sonenberg, N. and Bell, J.C. 1999. Characterization of transgenic mice with targeted disruption of the catalytic domain of PKR. J Biol Chem 274: 5953-5962 Cuddihy A.R., Li S., Tam N.W., Wong A.H., Taya Y., Abraham, N., Bell J.C. and Koromilas A.E. 1999. Double-stranded-RNA-activated protein kinase PKR enhances transcriptional activation by tumor suppressor p53. Mol Cell Biol 19(4):2475-84 Abraham, N., Jaramillo, M.L., Duncan, P.I., Méthot, N., Icely, P.L., Stojdl, D.F., Barber, G.N. and Bell, J.C. 1998. The murine PKR tumor suppressor gene is rearranged in a lymphocytic leukemia. Exp Cell Res 244:394-404 Abraham, N. and Bell, J.C. 1995. The Protein Kinase Factsbook: Protein-Serine Kinases. Academic Press. London. pp. 317-318 Jaramillo, M.L., Abraham, N. and Bell, J.C. 1995. The interferon system: a review with emphasis on the role of PKR in growth control. Cancer Invest 13:327-338