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Microbiology & Immunology Faculty
Research | Publications | Lab Members
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Kenneth M. Izumi, Ph.D.
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Research
Epstein-Barr virus (EBV) is associated with several human malignancies including a non-Hodgkin's lymphoma of AIDS patients and transplant recipients, Hodgkin's lymphoma, and Burkitt's lymphoma. In the malignant cells, EBV expresses nine proteins including latent infection membrane protein 1 (LMP1). LMP1 is required for EBV to transform primary B-lymphocytes into indefinitely proliferating cell lines and therefore is likely to be important in the pathogenesis of these lymphomas. The central hypothesis of our investigation is that LMP1 is constitutively activated receptor that drives B-cell proliferation by transducing signals that alter expression of specific cell genes. LMP1 transduces signals through tumor necrosis factor (TNF) receptor associated factors (TRAF), TNF receptor associated death domain protein (TRADD), and TNF receptor interacting protein (RIP) that activate NF-κB and mitogen activated protein kinases (MAPK). Our goal is to delineate the role of these signals in driving B-cell proliferation and to identify the specific cell genes whose expression is altered by LMP1 signals to transform B-cell growth. It is expected that the knowledge gained from such analyses will reveal targets for treating or preventing EBV-associated malignancies. Such results will be of additional significance because of what is also learned about the signaling pathways and cell genes that regulate B-cell growth.
Publications
- Izumi KM, Kaye KM, Kieff ED. The Epstein-Barr virus LMP1 amino acid sequence that engages tumor necrosis factor receptor associated factors is critical for primary B lymphocyte growth transformation. Proc Natl Acad Sci USA 1997. 94:1447-1452.
- Izumi KM, Kieff ED. The Epstein-Barr virus oncogene LMP1 engages TRADD to mediate B lymphocyte growth transformation and activate NF-κB. Proc Natl Acad Sci USA 1997. 94:12594-12597.
- Izumi KM, Cahir-McFarland E, Chen Y, Riley EA, Rizzo D, Kieff E. The residues between the two transformation effector sites of Epstein-Barr virus latent membrane protein 1 are not critical for B-lymphocyte growth transformation. J. Virol. 1999. 73:9908-9916.
- Kaye KM, Izumi, KM, Li, H, Johanssen E, Davidson D, Longnecker R, Kieff E. An Epstein-Barr virus that expresses only the first 231 LMP1 amino acids efficiently initiates primary B-lymphocyte growth transformation. J. Virol. 1999. 73:10525-10530.
- Izumi KM, McFarland EC, Ting AT, Riley EA, Seed B, Kieff E. The Epstein-Barr virus oncoprotein latent membrane protein 1 (LMP1) engages TNF receptor associated proteins TRADD and RIP but does not induce apoptosis or require RIP for NF-κB activation. Mol. Cell Biol. 1999. 19:5759-67.
- Higuchi, M., Kieff, E. Izumi, K.M. The Epstein-Barr virus latent membrane protein 1 (LMP1) putative Janus Kinase 3 (JAK3) binding domain does not mediate JAK3 association or activation in B-lymphoma or lymphoblastoid cell lines. J. Virol. 2002. 76:455-9.
- Higuchi, M., Izumi K.M., Kieff, E. Epstein-Barr virus latent-infection membrane proteins are palmitoylated and raft-associated: protein 1 binds to the cytoskeleton through TNF receptor cytoplasmic factors. Proc. Natl. Acad. Sci. USA 2001. 98:4675-80.
Lab Members
Lab Rooms: 5.041V
- Sarah Boyd, Research Associate
