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Louis R. Barrows

Associate Professor of Pharmacology and Toxicology

Education and Training

B.S., 1975, California Polytechnic State University

Ph.D., 1980, University of California, Irvine, Pharmacology.

Research Interests

My laboratory is dedicated to the discovery of new anticancer agents. Much of what we do can be considered natural products drug discovery. We identify new anticancer leads based on their novel mechanisms of action. In fact, a large part of our effort has been devoted to the development of new tests to characterize the candidate drugs. Extracts of organisms from coral reefs and tropical rain forests provide many of the molecules we evaluate. Determination of the molecular actions of the new molecules, and determination of the precise cellular consequences of their activity, has been the basis of several student projects. We take these new drugs all the way from the sponge to the sequencing gel, and then into tumor-bearing mice.

We also are very interested in the cellular targets of anti-cancer drugs, particularly in the physical interactions of these target molecules with drugs and with other cellular macromolecules. Description of drug binding sites and kinetics provides an understanding of how to modulate the function of the critical drug target molecules. Sites of interaction with other cellular macromolecules may identify new sites for drug action. About half the student projects in the lab are directed at identifying sites at which peptides from combinatorial libraries, or natural products, bind to and modulate the function of key drug targets. Inhibitors of specific targets are then tested in human tumor cells for activities predicted from their in vitro activity.

Selected Publications

Edler, M.C., Fernandez, A.M., Lassota, P., Ireland, C.M. and Barrows, L.R. Inhibition of Tubulin Polymerization by Vitilevuamide: a Bicyclic Marine Peptide that Inhibits Tubulin Polymerization at a Site Distinct from Colchicine, the Vinca Alkaloids and Dolastatin 10. Biochem. Pharm. 63: 707-715, 2002.

Matsumoto, S.S., Haughey, H.M., Schmehl, D.M., Venables, D.A., Ireland, C.M., Holden, J.A. and Barrows, L.R. Makaluvamine-DNA Topoisomerase II Interaction. Anti-Cancer Drugs 10:39-45, 1999.

Mitchell, A.M., Bayomi, A., Natarajan, E., Barrows, L.R., West, F.G. and Grissom, C.B. Targeting leukemia cells with cobalamin bioconjugates. Enzymatic Mechanisms 1:150-154, 1999.

Pond, C.D., Li, X.-G., Rubin, E.H. and Barrows, L.R. Effects of mutations in the F361 to R364 region of topoisomerase I (Topo I), in the presence and absence of 9-aminocamptothecin, on the Topo I-DNA interaction. Anti-Cancer Drugs 10:647-653, 1999.

Fernandez, A.F., He, H.-Y., McDonald, L.A., Lassota, P., Discafani, C., Sorenson, E.F., Edler, M.C., Barrows, L.R., Clardy, J.C., and Ireland, C.M. Structural studies of marine peptides. Pure and Appl. Chem. 70:2130-2139, 1998.

Barrows, L.R., Holden, J.A., Anderson, M. and D'Arpa, P. The CHO mutant, EM9, deficient in DNA ligase III activity, exhibits hypersensitivity to camptothecin independent of DNA replication. Mutat. Res. 408:103-110, 1998.

Pharmacology & Toxicology   College of Pharmacy   30 S. 2000 E., Rm 201, SLC  UT 84112  phone: 801-581-6287  fax: 801-585-5111 phtx@pharm.utah.edu