We have three main areas of interest, all involving the study of malaria parasites, the cause of one of the most important infections of humans. First, we study the basic biology of malaria parasites, in particular the biochemical properties and biological roles of proteases. Key projects include the biochemical characterization of cysteine proteases, the evaluation of the biological roles of these enzymes using cell biology and genetic techniques, the characterization of intracellular targeting of proteases, and the antimalarial mechanism of action of antibiotics. Second, in collaboration with a number of industry and academic groups, we are pursuing drug discovery, evaluating protease inhibitors and other compounds as potential antimalarial drugs. Third, we study malaria in Africa, with projects in Uganda and Burkina Faso evaluating the antimalarial efficacy of new antimalarial regimens and translational studies evaluating the molecular epidemiology of malaria, the roles of host and parasite genetic polymorphisms in treatment outcomes, antimalarial immune responses, antigenic diversity in clinical isolates, the interaction of malaria and HIV infection, and related areas.
Pandey KC, Sijwali PS, Singh A., Na B-K, Rosenthal PJ: Independent intramolecular mediators of folding, activity, and inhibition for the Plasmodium falciparum cysteine protease falcipain-2. J Biol Chem, 279:3484-3491, 2004.
Sijwali PS, Rosenthal PJ: Gene disruption confirms a critical role for the cysteine protease falcipain-2 i n hemoglobin hydrolysis by Plasmodium falciparum . Proc Natl Acad Sci USA, 101:4384-4389, 2004.
Sijwali PS, Kato K, Seydel KB, Gut J, Lehman J, Klemba M, Goldberg DE, Miller LH, Rosenthal PJ: Plasmodium falciparum cysteine protease falcipain-1 is not essential in erythrocytic stage malaria parasites. Proc Natl Acad Sci USA, 101:8721-8726, 2004.
Singh AK, Rosenthal PJ: Selection of cysteine protease inhibitor resistant malaria parasites is accompanied by amplification of falcipain genes and alteration in inhibitor transport. J Biol Chem, 279:35236-42, 2004 .
Staedke SG, Mpimbaza A, Kamya MR, Nzarubara BK, Dorsey G, Rosenthal PJ: Combination therapies for uncomplicated falciparum malaria in Kampala, Uganda: a randomized clinical trial. Lancet, 364:1950-1957, 2004.
Pandey KC, Wang SX, Sijwali PS, Lau AL, McKerrow JH, Rosenthal PJ: The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motif. Proc Natl Acad Sci USA, 102:9138-9143, 2005.