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Faculty
Research InterestsOur laboratory is interested in the control of cell survival by the iap (inhibitor of apoptosis) gene family, which encodes a group of factors with diverse cellular functions that range from suppression of apoptotic cell death by direct inhibition of apoptotic effector proteases to the control of mitotic spindle formation in conjunction with mitosis-regulated kinases. Our work is focused on X-linked IAP (XIAP), a potent inhibitor of apoptosis that has been shown to play roles in apoptosis inhibition, cell cycle control, activation of stress-induced transcription factors and stress-activated kinases, cytokine signaling, protein degradation through the ubiquitin pathway and even the metabolic control of intracellular copper levels. A major effort in our laboratory is to reconcile these apparently diverse properties of XIAP. Through the characterization of XIAP-deficient mice, mutagenesis analysis, imaging studies of intracellular trafficking and the identification of novel XIAP-associated proteins, we are beginning to understand which of these functions can, and cannot, be uncoupled from each other. Our long-term goal is to describe an integrated picture of XIAP in which its disparate functions can be reconciled. Education1986-1989 University of London, Queen Mary College, London, England, B.Sc. with Honours in Molecular Biology 1989-1993 Howard Hughes Medical Institute, The University of Michigan and University of London, St. George's Hospital Medical School, Ph.D. in Biochemistry (University of London). Mentor: Dr. Gary Nabel. Postdoctoral Training1994-1997 Postdoctoral Fellow, Howard Hughes Medical Institute, Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago. Mentor: Dr. Craig Thompson. Honors and Awards1990-1993 Training Award: British Medical Research Council AIDS Directed Programme Fellow 1993-1995 Training Award: Howard Hughes Medical Institute Postdoctoral Fellow 1995-1997 Training Award: National Cancer Institute Postdoctoral Fellow 1997 Training Award: Leukemia Society of America Special Fellow 1999-2001 Training Award: Intramural Research Award, National Cancer Institute, NIH 2002 Training Award: University of Michigan Biomedical Scholar Award Recent PublicationsWilkinson, J. C., Cepero, E., Boise, L.H. and Duckett, C.S. Upstream regulatory role for XIAP in receptor-mediated apoptosis. Mol. Cell. Biol. 24:7003-7014 (2004). Lewis, J., Burstein, E., Birkey Reffey, S., Bratton, S.B., Roberts, A.B., and Duckett, C. S. Uncoupling of the signaling and caspase-inhibitory properties of XIAP. J. Biol. Chem 279:4877-4886 (2004). Burstein, E., Ganesh, L., Dick, R.D., van De Sluis, B., Wilkinson, J.C., Lewis, J., Klomp, L.W.J., Wijmenga, C., Brewer, G.J., Nabel, G.J. and Duckett, C.S. A novel role for XIAP in copper homeostasis through regulation of MURR1. EMBO J. 23:244-254 (2004). Ganesh, L., Burstein, E., Guha-Niyogi, A., Louder, M., Mascola, J., Klomp, L.W.J., Wijmenga, C., Duckett, C. S. and Nabel, G.J. The gene product, Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes. Nature426:853-857 (2003). Lab ProjectsPlease contact Dr. Duckett for information regarding current research projects. Additional Lab Links Department of Pathology
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