Colin Duckett, Ph.D.
Associate Professor, Department of Pathology
and Department of Internal Medicine
Associate Director, Molecular Mechanisms of Disease Program

http://web.mac.com/csd66/iWeb/lab/Home.html

colind@umich.edu

Research Interests

The focus of our laboratory is the study of apoptosis, a biochemically ordered process in which cells are induced to initiate a cellular suicide program in response to physiologic cues, cellular damage, or virus infection. In normal cells the apoptotic pathway is very tightly controlled, but deregulation of the cell death cascade contributes to the pathogenesis of many human diseases including cancer, neurodegenerative diseases and lymphoproliferative and autoimmune disorders.

Our laboratory is interested in the control of cell survival is focused on the iap (inhibitor of apoptosis) gene family 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.

REPRESENTATIVE PUBLICATIONS

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. Nature 426:853-857 (2003).

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).

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. 279:9023-9029 (2004).

Wilkinson, J. C., Cepero, E., Boise, L.H. and Duckett, C.S. An upstream regulatory role for XIAP in receptor-mediated apoptosis. Mol. Cell. Biol., 2004 Aug;24(16):7003-14. .

Wright CW, Rumble JM, Duckett CS. CD30 activates both the canonical and alternative NF-kappaB pathways in anaplastic large cell lymphoma cells. J Biol Chem. 2007 Apr;282(14):10252-62. Epub 2007 Jan 29. PMID: 17261581 [PubMed - indexed for MEDLINE]

Mufti AR, Burstein E, Csomos RA, Graf PC, Wilkinson JC, Dick RD, Challa M, Son JK, Bratton SB, Su GL, Brewer GJ, Jakob U, Duckett CS.
XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders. Mol Cell. 2006 Mar 17;21(6):775-85.

Burstein E, Hoberg JE, Wilkinson AS, Rumble JM, Csomos RA, Komarck CM, Maine GN, Wilkinson JC, Mayo MW, Duckett CS. COMMD proteins, a novel family of structural and functional homologs of MURR1. J Biol Chem. 2005 Jun 10;280(23):22222-32.