Department of Chemistry

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UNC-CH Collaborators

Steve Matson

Vytas Bankaitis

Nancy Thompson

Elizabeth Wilson

Matthew Wolfgang

Muhammad Yousaf

Matthew R. Redinbo

Professor of Chemistry, Biochemistry and Biophysics

redinbo@unc.edu
919-843-8910
919-962-3675 (fax)
Kenan Labs B929

Research Interests

Structural Studies of Dynamic Cellular Processes

Professional Background

University of Washington, Seattle; Postdoctoral, 1995-1999. University of California, Los Angeles; Ph.D., 1995. University of California, Davis; B.S., 1990. Burroughs Wellcome Career Award in the Biomedical Sciences 1999-2005.

Research Synopsis

My group uses the tools of structural, molecular and chemical biology to examine dynamic cellular and systemic processes. We are currently focused on three central areas:

Nuclear Receptors in Transcriptional Control
Ligand-regulated intracellular nuclear receptors are central mediators of gene expression and are the target of a wide variety of therapeutic compounds. My group has conducted pioneering studies on PXR, the primary xenobiotic receptor in human tissues, and LRH-1, which plays a critical role in breast cancer development. We are currently pursuing the structures of several transcriptional active complexes centered around nuclear receptors.

		DNA Manipulation Enzymes
		The management of DNA topology and the movement of DNA duplexes are difficult catalytic and engineering problems that cells attack in a variety of ways. We have elucidated how human DNA topoisomerase I relaxes superhelical tension and is poisoned by the camptothecin class of anticancer drugs. We are now unraveling the structural basis of DNA movement within and between cells.

Drug Metabolism Systems
The recognition, processing and elimination of therapeutic compounds significantly impacts the efficacy and side effects of clinical interventions. We have examined the activation of anticancer drugs, as well as the elimination of dangerous narcotics like heroin and cocaine by promiscuous human drug metabolism enzymes. We continue with novel studies on distinct xenobiotic processing proteins.

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Selected References

Lujan, S.A., Guogas, L.M., Ragonese, H., Matson, S.W., and Redinbo, M.R. (2007). Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase. Proceedings of the National Academy of Sciences USA, 104, 12282-12287.

Ortlund, E.A., Bridgham, J.T., Redinbo, M.R., and Thornton, J.W. (2007). Crystal structure of an ancient protein: evolution by conformational epistasis. Science, 317, 1544-1548.

Ortlund, E.A., Lee, Y., Solomon, I.H., Hager, J.M., Safi, R., Choi, Y., Guan, Z., Tripathy, A., Raetz, C.R.H., McDonnell, D.P., Moore, D.D., and Redinbo, M.R. (2005). Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP. Nature Structural and Molecular Biology, 12, 357-363.

Bencharit, S., Morton, C.L., Potter, P.M. and Redinbo, M.R. (2003). Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nature Structural Biology, 10, 349-356.

Lesher, D.-T.T., Pommier, Y., Stewart, L., and Redinbo, M.R. (2002). 8-oxoguanine rearranges the active site of human topoisomerase I.Proceedings of the National Academy of Sciences USA, 99, 12102-12107.

Bencharit, S., Morton, C.L., Howard-Williams, E.L., Danks, M.K., Potter, P.M., and Redinbo, M.R. (2002). Structural insights into CPT-11 activation by mammalian carboxylesterases. Nature Structural Biology, 9, 337-342.

Watkins, R.E., Wisely, G.B., Moore, L.B., Collins, J.L., Lambert, M.H., Williams, S.P., Willson, T.M., Kliewer, S.A., and Redinbo, M.R. (2001). The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science, 292, 2329-2333.

Department of Chemistry
Campus Box 3290
Caudill and Kenan Laboratories
The University of North Carolina at Chapel Hill
Chapel Hill, NC 27599-3290 USA
Phone: (919) 843-7100