Philip Rosenthal, MD
Associate Director, UCSF-Gladstone CFAR
Professor, School of Medicine
Email: prosenthal@medsfgh.ucsf.edu
Biography
We have three main areas of interest, all involving malaria, one of the most important infections of humans. First, we study the basic biology of malaria parasites, including the biochemical properties and biological roles of parasite proteases and mechanisms of action of novel antimalarial agents. Second, in collaboration with industry and academic groups, we are pursuing drug discovery, evaluating protease inhibitors, oxaboroles, and other compounds as potential antimalarial drugs. Third, we study malaria in Africa, with translational and laboratory studies at UCSF and in Uganda and Burkina Faso evaluating antimalarial drug efficacy and resistance, the molecular epidemiology of malaria, the roles of host and parasite genetic polymorphisms in treatment outcomes, antimalarial pharmacokinetics and pharmacodynamics, and related areas. Finally, a new area of interest is using genetic tools to characterize causes of febrile illness in African children. In other activities, Dr. Rosenthal is Editor-in-Chief of the American Journal of Tropical Medicine and Hygiene; Chair, Scientific Advisory Committee, WorldWide Antimalarial Resistance Network; Member, Scientific Board, Infectious Diseases Data Observatory; and a member of the World Health Organization Technical Expert Group on Malaria Chemotherapy.
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- Staedke SG, Mpimbaza A, Kamya MR, Nzarubara BK, Dorsey G, Rosenthal PJ. Combination treatments for uncomplicated falciparum malaria in Kampala, Uganda: randomised clinical trial. Lancet. 2004 Nov 27-Dec 3; 364(9449):1950-7.
- Na BK, Kim TS, Rosenthal PJ, Lee JK, Kong Y. Evaluation of cysteine proteases of Plasmodium vivax as antimalarial drug targets: sequence analysis and sensitivity to cysteine protease inhibitors. Parasitol Res. 2004 Oct; 94(4):312-7.
- Go ML, Liu M, Wilairat P, Rosenthal PJ, Saliba KJ, Kirk K. Antiplasmodial chalcones inhibit sorbitol-induced hemolysis of Plasmodium falciparum-infected erythrocytes. Antimicrob Agents Chemother. 2004 Sep; 48(9):3241-5.
- Musonda CC, Taylor D, Lehman J, Gut J, Rosenthal PJ, Chibale K. Application of multi-component reactions to antimalarial drug discovery. Part 1: Parallel synthesis and antiplasmodial activity of new 4-aminoquinoline Ugi adducts. Bioorg Med Chem Lett. 2004 Aug 02; 14(15):3901-5.
- Singh A, 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. 2004 Aug 20; 279(34):35236-41.
- Greenbaum DC, Mackey Z, Hansell E, Doyle P, Gut J, Caffrey CR, Lehrman J, Rosenthal PJ, McKerrow JH, Chibale K. Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi. J Med Chem. 2004 Jun 03; 47(12):3212-9.
- Fidock DA, Rosenthal PJ, Croft SL, Brun R, Nwaka S. Antimalarial drug discovery: efficacy models for compound screening. Nat Rev Drug Discov. 2004 Jun; 3(6):509-20.
- 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 U S A. 2004 Jun 08; 101(23):8721-6.
- Nsobya SL, Parikh S, Kironde F, Lubega G, Kamya MR, Rosenthal PJ, Dorsey G. Molecular evaluation of the natural history of asymptomatic parasitemia in Ugandan children. J Infect Dis. 2004 Jun 15; 189(12):2220-6.
- Staedke SG, Sendagire H, Lamola S, Kamya MR, Dorsey G, Rosenthal PJ. Relationship between age, molecular markers, and response to sulphadoxine-pyrimethamine treatment in Kampala, Uganda. Trop Med Int Health. 2004 May; 9(5):624-9.
- Sijwali PS, Rosenthal PJ. Gene disruption confirms a critical role for the cysteine protease falcipain-2 in hemoglobin hydrolysis by Plasmodium falciparum. Proc Natl Acad Sci U S A. 2004 Mar 30; 101(13):4384-9.
- Na BK, Shenai BR, Sijwali PS, Choe Y, Pandey KC, Singh A, Craik CS, Rosenthal PJ. Identification and biochemical characterization of vivapains, cysteine proteases of the malaria parasite Plasmodium vivax. Biochem J. 2004 Mar 01; 378(Pt 2):529-38.
- Locher CP, Ruben PC, Gut J, Rosenthal PJ. 5HT1A serotonin receptor agonists inhibit Plasmodium falciparum by blocking a membrane channel. Antimicrob Agents Chemother. 2003 Dec; 47(12):3806-9.
- Lee BJ, Singh A, Chiang P, Kemp SJ, Goldman EA, Weinhouse MI, Vlasuk GP, Rosenthal PJ. Antimalarial activities of novel synthetic cysteine protease inhibitors. Antimicrob Agents Chemother. 2003 Dec; 47(12):3810-4.
- Boyom FF, Ngouana V, Zollo PH, Menut C, Bessiere JM, Gut J, Rosenthal PJ. Composition and anti-plasmodial activities of essential oils from some Cameroonian medicinal plants. Phytochemistry. 2003 Dec; 64(7):1269-75.
- Pandey KC, Sijwali PS, Singh A, Na BK, Rosenthal PJ. Independent intramolecular mediators of folding, activity, and inhibition for the Plasmodium falciparum cysteine protease falcipain-2. J Biol Chem. 2004 Jan 30; 279(5):3484-91.
- Rosenthal PJ. Antimalarial drug discovery: old and new approaches. J Exp Biol. 2003 Nov; 206(Pt 21):3735-44.
- Chiyanzu I, Hansell E, Gut J, Rosenthal PJ, McKerrow JH, Chibale K. Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain. Bioorg Med Chem Lett. 2003 Oct 20; 13(20):3527-30.
- Dorsey G, Vlahos J, Kamya MR, Staedke SG, Rosenthal PJ. Prevention of increasing rates of treatment failure by combining sulfadoxine-pyrimethamine with artesunate or amodiaquine for the sequential treatment of malaria. J Infect Dis. 2003 Oct 15; 188(8):1231-8.
- Staedke SG, Nottingham EW, Cox J, Kamya MR, Rosenthal PJ, Dorsey G. Short report: proximity to mosquito breeding sites as a risk factor for clinical malaria episodes in an urban cohort of Ugandan children. Am J Trop Med Hyg. 2003 Sep; 69(3):244-6.
- Kyabayinze D, Cattamanchi A, Kamya MR, Rosenthal PJ, Dorsey G. Validation of a simplified method for using molecular markers to predict sulfadoxine-pyrimethamine treatment failure in African children with falciparum malaria. Am J Trop Med Hyg. 2003 Sep; 69(3):247-52.
- Batra S, Sabnis YA, Rosenthal PJ, Avery MA. Structure-based approach to falcipain-2 inhibitors: synthesis and biological evaluation of 1,6,7-trisubstituted dihydroisoquinolines and isoquinolines. Bioorg Med Chem. 2003 May 15; 11(10):2293-9.
- Sabnis YA, Desai PV, Rosenthal PJ, Avery MA. Probing the structure of falcipain-3, a cysteine protease from Plasmodium falciparum: comparative protein modeling and docking studies. Protein Sci. 2003 Mar; 12(3):501-9.
- Gasasira AF, Dorsey G, Nzarubara B, Staedke SG, Nassali A, Rosenthal PJ, Kamya MR. Comparative efficacy of aminoquinoline-antifolate combinations for the treatment of uncomplicated falciparum malaria in Kampala, Uganda. Am J Trop Med Hyg. 2003 Feb; 68(2):127-32.
- Cattamanchi A, Kyabayinze D, Hubbard A, Rosenthal PJ, Dorsey G. Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of msp-1, msp-2, and glurp. Am J Trop Med Hyg. 2003 Feb; 68(2):133-9.