Philip Rosenthal, MD

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Philip Rosenthal, MD

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Associate Director, UCSF-Gladstone CFAR
Professor, School of Medicine
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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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  1. Gasasira AF, Kamya MR, Ochong EO, Vora N, Achan J, Charlebois E, Ruel T, Kateera F, Meya DN, Havlir D, Rosenthal PJ, Dorsey G. Effect of trimethoprim-sulphamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance. Malar J. 2010 Jun 23; 9:177.
  2. Achan J, Tibenderana JK, Kyabayinze D, Wabwire Mangen F, Kamya MR, Dorsey G, D'Alessandro U, Rosenthal PJ, Talisuna AO. Effectiveness of quinine versus artemether-lumefantrine for treating uncomplicated falciparum malaria in Ugandan children: randomised trial. BMJ. 2009 Jul 21; 339:b2763.
  3. Kerr ID, Lee JH, Farady CJ, Marion R, Rickert M, Sajid M, Pandey KC, Caffrey CR, Legac J, Hansell E, McKerrow JH, Craik CS, Rosenthal PJ, Brinen LS. Vinyl sulfones as antiparasitic agents and a structural basis for drug design. J Biol Chem. 2009 Sep 18; 284(38):25697-703.
  4. Arico-Muendel C, Centrella PA, Contonio BD, Morgan BA, O'Donovan G, Paradise CL, Skinner SR, Sluboski B, Svendsen JL, White KF, Debnath A, Gut J, Wilson N, McKerrow JH, DeRisi JL, Rosenthal PJ, Chiang PK. Antiparasitic activities of novel, orally available fumagillin analogs. Bioorg Med Chem Lett. 2009 Sep 01; 19(17):5128-31.
  5. Mpimbaza A, Staedke SG, Ndeezi G, Byarugaba J, Rosenthal PJ. Predictors of anti-convulsant treatment failure in children presenting with malaria and prolonged seizures in Kampala, Uganda. Malar J. 2009 Jun 29; 8:145.
  6. Pandey KC, Barkan DT, Sali A, Rosenthal PJ. Regulatory elements within the prodomain of Falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum. PLoS One. 2009 May 27; 4(5):e5694.
  7. Rodrigues T, Guedes RC, dos Santos DJ, Carrasco M, Gut J, Rosenthal PJ, Moreira R, Lopes F. Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials. Bioorg Med Chem Lett. 2009 Jul 01; 19(13):3476-80.
  8. Capela R, Oliveira R, Gonçalves LM, Domingos A, Gut J, Rosenthal PJ, Lopes F, Moreira R. Artemisinin-dipeptidyl vinyl sulfone hybrid molecules: design, synthesis and preliminary SAR for antiplasmodial activity and falcipain-2 inhibition. Bioorg Med Chem Lett. 2009 Jun 15; 19(12):3229-32.
  9. Subramanian S, Hardt M, Choe Y, Niles RK, Johansen EB, Legac J, Gut J, Kerr ID, Craik CS, Rosenthal PJ. Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3. PLoS One. 2009; 4(4):e5156.
  10. Staedke SG, Mwebaza N, Kamya MR, Clark TD, Dorsey G, Rosenthal PJ, Whitty CJ. Home management of malaria with artemether-lumefantrine compared with standard care in urban Ugandan children: a randomised controlled trial. Lancet. 2009 May 09; 373(9675):1623-31.
  11. Mobula L, Lilley B, Tshefu AK, Rosenthal PJ. Resistance-mediating polymorphisms in Plasmodium falciparum infections in Kinshasa, Democratic Republic of the Congo. Am J Trop Med Hyg. 2009 Apr; 80(4):555-8.
  12. Boyom FF, Kemgne EM, Tepongning R, Ngouana V, Mbacham WF, Tsamo E, Zollo PH, Gut J, Rosenthal PJ. Antiplasmodial activity of extracts from seven medicinal plants used in malaria treatment in Cameroon. J Ethnopharmacol. 2009 Jun 25; 123(3):483-8.
  13. Noungoue DT, Chaabi M, Ngouela S, Antheaume C, Boyom FF, Gut J, Rosenthal PJ, Lobstein A, Tsamo E. Antimalarial compounds from the stem bark of Vismia laurentii. Z Naturforsch C J Biosci. 2009 Mar-Apr; 64(3-4):210-4.
  14. Greenhouse B, Slater M, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Clark TD, Staedke SG, Kamya MR, Hubbard A, Rosenthal PJ, Dorsey G. Decreasing efficacy of antimalarial combination therapy in Uganda is explained by decreasing host immunity rather than increasing drug resistance. J Infect Dis. 2009 Mar 01; 199(5):758-65.
  15. Kerr ID, Lee JH, Pandey KC, Harrison A, Sajid M, Rosenthal PJ, Brinen LS. Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: implications for substrate specificity. J Med Chem. 2009 Feb 12; 52(3):852-7.
  16. German P, Parikh S, Lawrence J, Dorsey G, Rosenthal PJ, Havlir D, Charlebois E, Hanpithakpong W, Lindegardh N, Aweeka FT. Lopinavir/ritonavir affects pharmacokinetic exposure of artemether/lumefantrine in HIV-uninfected healthy volunteers. J Acquir Immune Defic Syndr. 2009 Aug 01; 51(4):424-9.
  17. Dude MA, Kaeppler U, Herb M, Schiller M, Schulz F, Vedder B, Heppner S, Pradel G, Gut J, Rosenthal PJ, Schirmeister T, Leippe M, Gelhaus C. Synthesis and evaluation of non-peptidic cysteine protease inhibitors of P. falciparum derived from etacrynic acid. Molecules. 2008 Dec 23; 14(1):19-35.
  18. McKerrow JH, Rosenthal PJ, Swenerton R, Doyle P. Development of protease inhibitors for protozoan infections. Curr Opin Infect Dis. 2008 Dec; 21(6):668-72.
  19. Nsobya SL, Kiggundu M, Joloba M, Dorsey G, Rosenthal PJ. Complexity of Plasmodium falciparum clinical samples from Uganda during short-term culture. J Infect Dis. 2008 Nov 15; 198(10):1554-7.
  20. Parikh S, Rosenthal PJ. Human genetics and malaria: relevance for the design of clinical trials. J Infect Dis. 2008 Nov 01; 198(9):1255-7.
  21. Dominguez JN, Leon C, Rodrigues J, Gamboa de Dominguez N, Gut J, Rosenthal PJ. Synthesis of chlorovinyl sulfones as structural analogs of chalcones and their antiplasmodial activities. Eur J Med Chem. 2009 Apr; 44(4):1457-62.
  22. Kim CC, Parikh S, Sun JC, Myrick A, Lanier LL, Rosenthal PJ, DeRisi JL. Experimental malaria infection triggers early expansion of natural killer cells. Infect Immun. 2008 Dec; 76(12):5873-82.
  23. Clark TD, Greenhouse B, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Staedke SG, Seto E, Kamya MR, Rosenthal PJ, Dorsey G. Factors determining the heterogeneity of malaria incidence in children in Kampala, Uganda. J Infect Dis. 2008 Aug 01; 198(3):393-400.
  24. Yeka A, Dorsey G, Kamya MR, Talisuna A, Lugemwa M, Rwakimari JB, Staedke SG, Rosenthal PJ, Wabwire-Mangen F, Bukirwa H. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treating uncomplicated malaria: a randomized trial to guide policy in Uganda. PLoS One. 2008 Jun 11; 3(6):e2390.
  25. Staedke SG, Jagannathan P, Yeka A, Bukirwa H, Banek K, Maiteki-Sebuguzi C, Clark TD, Nzarubara B, Njama-Meya D, Mpimbaza A, Rosenthal PJ, Kamya MR, Wabwire-Mangen F, Dorsey G, Talisuna AO. Monitoring antimalarial safety and tolerability in clinical trials: a case study from Uganda. Malar J. 2008 Jun 11; 7:107.