OHSU

Riscoe Lab

Overview

Dr. Michael Riscoe is the director of the Experimental Chemotherapy Laboratory and he is a professor in the Molecular Microbiology and Immunology Department at Oregon Health Sciences University.  Dr. Riscoe's laboratory focuses on the discovery, optimization and development of antiparasitic drugs, especially drugs for treatment and prevention of malaria. Using modern methods of chemical synthesis and drug design his laboratory has developed novel antimalarial chemotypes that are orally bioavailable and curative in mouse models of malaria. Examples of these drugs include: (1) dual functional acridones with blood stage activity that interact synergistically with 4-aminoquinolines such as chloroquine, (2) 4(1H)-quinolones that block parasite respiration and act against the blood, liver, and gametocyte (i.e., transmission stage) stages of parasite development, and (3) 4-aminoquinoline derivatives (so-called "Pharmachins"), designed to replace chloroquine, which are active against multidrug resistant strains and at least 10 times more potent than chloroquine against malaria in mice.  His research team also employs the techniques of biochemistry, molecular biology, biophysics, and pharmacology to explore mechanisms of drug action and resistance. 

Dr. Riscoe's laboratory receives support from the Department of Veterans Affairs, National Institutes of Health, and the Medicines for Malaria Venture and he maintains an active collaboration with members of the Division of Experimental Therapeutics at the Walter Reed Army Institute for Research. He continues to serve as a reviewer of the US DOD's Military Infectious Diseases Research Program (MIDRP).  The long-term objective of Dr. Riscoe's malaria research is to develop drugs that are inexpensive, safe and curative in treatment of the most vulnerable populations, young children and pregnant women, and ultimately to develop a cocktail of drugs that may be used to eradicate the disease.



Recent Publications

Kelly, JX, Smilkstein, MJ, Brun, R, Wittlin, S, Cooper, RA, Lane, KD, Janowsky, A, Johnson, RA, Dodean, RA, Winter, R, Hinrichs, DJ, and Riscoe, MK,, 2009, Discovery of a Novel Antimalarial Chemotype: Dual-function Acridone Derivatives, Nature 459: 270-273. Download

Guiguemde WA, Shelat AA, Bouck D, Duffy S, Crowther GJ, Davis PH, Smithson DC, Connelly M, Clark J, Zhu F, Jiménez-Díaz MB, Martinez MS, Wilson EB, Tripathi AK, Gut J, Sharlow ER, Bathurst I, El Mazouni F, Fowble JW, Forquer I, McGinley PL, Castro S, Angulo-Barturen I, Ferrer S, Rosenthal PJ, Derisi JL, Sullivan DJ, Lazo JS, Roos DS, Riscoe MK, Phillips MA, Rathod PK, Van Voorhis WC, Avery VM, Guy RK, 2010, Chemical genetics of Plasmodium falciparum. Nature 465: 311-5. Download

Winter, RW, Kelly, JX, Smilkstein, MJ, Koop, DR, Hinrichs, DJ and Riscoe, MK, 2011, Optimization of Endochin-like Quinolones for Antimalarial Activity. Experimental Parasitology 127:545-551. Download

Pou S, Winter, RW, Nilsen, A, Kelly, JX, Li, Y, Doggett, JS, Riscoe, EW, Wegmann, KW, Hinrichs, DJ, and Riscoe, MK, 2012. Sontochin as a guide to development of drugs against chloroquine resistant malaria. Antimicrobial Agents and Chemotherapy 56(7):3475-80. Download

Doggett, JS, Nilsen, A, Forquer, I, Wegmann, KW, Jones-Brando, L, Yolken, RH, Bordon, C, Charman, SA, Katneni, K, Schultz T, Burrows, J, Hinrichs, DJ, Meunier B, Carruthers, VB, and Riscoe, MK, 2012. Endochin-like quinolones are highly efficacious against acute and latent experimental toxoplasmosis. Proceedings of the National Academy of Science, USA. 109(39):15936-41. Download

A. Nilsen, A. N. LaCrue, K. L. White, I. P. Forquer, R. M. Cross, J. Marfurt, M. W. Mather, M. J. Delves, D. M. Shackleford, F. E. Saenz, J. M. Morrisey, J. Steuten, T. Mutka, Y. Li,  G. Wirjanata, E. Ryan, S. Duffy, J. X. Kelly, B. F. Sebayang, A.-M. Zeeman, R. Noviyanti, R. E. Sinden, C. H. M. Kocken, R. N. Price, V. M. Avery, I. Angulo-Barturen, M. B. Jiménez-Díaz, S. Ferrer, E. Herreros, L. M. Sanz, F.-J. Gamo, I. Bathurst, J. N. Burrows, P. Siegl, R. K. Guy, R. W. Winter, A. B. Vaidya, S. A. Charman, D. E. Kyle, R. Manetsch, M. K. Riscoe, 2013, Quinolone-3-diarylethers: A new class of antimalarial drug. Science Translational Medicine 5, 177ra37. Download

Aaron Nilsen, Galen P. Miley, Isaac P. Forquer, Michael W. Mather, Kasiram Katneni, Yuexin Li, Sovitj Pou, April M. Pershing, Allison M. Stickles, Eileen Ryan, Jane Xu Kelly, J. Stone Doggett, Karen L. White, David J. Hinrichs, Rolf W. Winter, Susan A. Charman, Lev N. Zakharov, Ian Bathurst, Jeremy N. Burrows, Akhil B. Vaidya, and Michael K. Riscoe, 2014, Discovery, Synthesis, and Optimization of Antimalarial 4(1H)-Quinolone-3-Diarylethers. Journal of Medicinal Chemistry 57 (9), 3818-3834. Download