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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- Valente C, Guedes RC, Moreira R, Iley J, Gut J, Rosenthal PJ. Dipeptide vinyl sultams: synthesis via the Wittig-Horner reaction and activity against papain, falcipain-2 and Plasmodium falciparum. Bioorg Med Chem Lett. 2006 Aug 01; 16(15):4115-9.
- Musonda CC, Gut J, Rosenthal PJ, Yardley V, Carvalho de Souza RC, Chibale K. Application of multicomponent reactions to antimalarial drug discovery. Part 2: New antiplasmodial and antitrypanosomal 4-aminoquinoline gamma- and delta-lactams via a 'catch and release' protocol. Bioorg Med Chem. 2006 Aug 15; 14(16):5605-15.
- Dokomajilar C, Nsobya SL, Greenhouse B, Rosenthal PJ, Dorsey G. Selection of Plasmodium falciparum pfmdr1 alleles following therapy with artemether-lumefantrine in an area of Uganda where malaria is highly endemic. Antimicrob Agents Chemother. 2006 May; 50(5):1893-5.
- Myrick A, Leemann E, Dokomajilar C, Hopkins H, Dorsey G, Kamya MR, Rosenthal PJ. Short report: Dynamics of Plasmodium falciparum malaria after sub-optimal therapy in Uganda. Am J Trop Med Hyg. 2006 May; 74(5):758-61.
- Lee SA, Yeka A, Nsobya SL, Dokomajilar C, Rosenthal PJ, Talisuna A, Dorsey G. Complexity of Plasmodium falciparum infections and antimalarial drug efficacy at 7 sites in Uganda. J Infect Dis. 2006 Apr 15; 193(8):1160-3.
- Desai PV, Patny A, Gut J, Rosenthal PJ, Tekwani B, Srivastava A, Avery M. Identification of novel parasitic cysteine protease inhibitors by use of virtual screening. 2. The available chemical directory. J Med Chem. 2006 Mar 09; 49(5):1576-84.
- Francis D, Nsobya SL, Talisuna A, Yeka A, Kamya MR, Machekano R, Dokomajilar C, Rosenthal PJ, Dorsey G. Geographic differences in antimalarial drug efficacy in Uganda are explained by differences in endemicity and not by known molecular markers of drug resistance. J Infect Dis. 2006 Apr 01; 193(7):978-86.
- Eggena MP, Hopkins H, Barugahare B, Okello M, Ssali F, Mugyenyi P, Rosenthal PJ, Cao H, Dorsey G. CD4 T cell activation as a predictor for treatment failure in Ugandans with Plasmodium falciparum malaria. Am J Trop Med Hyg. 2006 Jan; 74(1):41-3.
- Ngouela S, Lenta BN, Noungoue DT, Ngoupayo J, Boyom FF, Tsamo E, Gut J, Rosenthal PJ, Connolly JD. Anti-plasmodial and antioxidant activities of constituents of the seed shells of Symphonia globulifera Linn f. Phytochemistry. 2006 Feb; 67(3):302-6.
- Singh N, Sijwali PS, Pandey KC, Rosenthal PJ. Plasmodium falciparum: biochemical characterization of the cysteine protease falcipain-2'. Exp Parasitol. 2006 Mar; 112(3):187-92.
- Kamya MR, Gasasira AF, Yeka A, Bakyaita N, Nsobya SL, Francis D, Rosenthal PJ, Dorsey G, Havlir D. Effect of HIV-1 infection on antimalarial treatment outcomes in Uganda: a population-based study. J Infect Dis. 2006 Jan 01; 193(1):9-15.
- Zongo I, Dorsey G, Rouamba N, Dokomajilar C, Lankoande M, Ouedraogo JB, Rosenthal PJ. Amodiaquine, sulfadoxine-pyrimethamine, and combination therapy for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso. Am J Trop Med Hyg. 2005 Nov; 73(5):826-32.
- Slater M, Kiggundu M, Dokomajilar C, Kamya MR, Bakyaita N, Talisuna A, Rosenthal PJ, Dorsey G. Distinguishing recrudescences from new infections in antimalarial clinical trials: major impact of interpretation of genotyping results on estimates of drug efficacy. Am J Trop Med Hyg. 2005 Aug; 73(2):256-62.
- Yeka A, Banek K, Bakyaita N, Staedke SG, Kamya MR, Talisuna A, Kironde F, Nsobya SL, Kilian A, Slater M, Reingold A, Rosenthal PJ, Wabwire-Mangen F, Dorsey G. Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda. PLoS Med. 2005 Jul; 2(7):e190.
- Parikh S, Gut J, Istvan E, Goldberg DE, Havlir DV, Rosenthal PJ. Antimalarial activity of human immunodeficiency virus type 1 protease inhibitors. Antimicrob Agents Chemother. 2005 Jul; 49(7):2983-5.
- 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 U S A. 2005 Jun 28; 102(26):9138-43.
- Domínguez JN, León C, Rodrigues J, Gamboa de Domínguez N, Gut J, Rosenthal PJ. Synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives. J Med Chem. 2005 May 19; 48(10):3654-8.
- Chiyanzu I, Clarkson C, Smith PJ, Lehman J, Gut J, Rosenthal PJ, Chibale K. Design, synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives. Bioorg Med Chem. 2005 May 02; 13(9):3249-61.
- Bakyaita N, Dorsey G, Yeka A, Banek K, Staedke SG, Kamya MR, Talisuna A, Kironde F, Nsobya S, Kilian A, Reingold A, Rosenthal PJ, Wabwire-Mangen F. Sulfadoxine-pyrimethamine plus chloroquine or amodiaquine for uncomplicated falciparum malaria: a randomized, multisite trial to guide national policy in Uganda. Am J Trop Med Hyg. 2005 May; 72(5):573-80.
- Domínguez JN, León C, Rodrigues J, Gamboa de Domínguez N, Gut J, Rosenthal PJ. Synthesis and antimalarial activity of sulfonamide chalcone derivatives. Farmaco. 2005 Apr; 60(4):307-11.
- Dahl EL, Rosenthal PJ. Biosynthesis, localization, and processing of falcipain cysteine proteases of Plasmodium falciparum. Mol Biochem Parasitol. 2005 Feb; 139(2):205-12.
- Fujii N, Mallari JP, Hansell EJ, Mackey Z, Doyle P, Zhou YM, Gut J, Rosenthal PJ, McKerrow JH, Guy RK. Discovery of potent thiosemicarbazone inhibitors of rhodesain and cruzain. Bioorg Med Chem Lett. 2005 Jan 03; 15(1):121-3.
- Rosenthal PJ. Cysteine proteases of malaria parasites. Int J Parasitol. 2004 Dec; 34(13-14):1489-99.
- Parikh S, Dorsey G, Rosenthal PJ. Host polymorphisms and the incidence of malaria in Ugandan children. Am J Trop Med Hyg. 2004 Dec; 71(6):750-3.
- Dorsey G, Dokomajilar C, Kiggundu M, Staedke SG, Kamya MR, Rosenthal PJ. Principal role of dihydropteroate synthase mutations in mediating resistance to sulfadoxine-pyrimethamine in single-drug and combination therapy of uncomplicated malaria in Uganda. Am J Trop Med Hyg. 2004 Dec; 71(6):758-63.