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. Guantai EM, Ncokazi K, Egan TJ, Gut J, Rosenthal PJ, Bhampidipati R, Kopinathan A, Smith PJ, Chibale K. Enone- and chalcone-chloroquinoline hybrid analogues: in silico guided design, synthesis, antiplasmodial activity, in vitro metabolism, and mechanistic studies. J Med Chem. 2011 May 26; 54(10):3637-49.
  2. Ang KK, Ratnam J, Gut J, Legac J, Hansell E, Mackey ZB, Skrzypczynska KM, Debnath A, Engel JC, Rosenthal PJ, McKerrow JH, Arkin MR, Renslo AR. Mining a cathepsin inhibitor library for new antiparasitic drug leads. PLoS Negl Trop Dis. 2011 May 03; 5(5):e1023.
  3. Shah F, Mukherjee P, Gut J, Legac J, Rosenthal PJ, Tekwani BL, Avery MA. Identification of novel malarial cysteine protease inhibitors using structure-based virtual screening of a focused cysteine protease inhibitor library. J Chem Inf Model. 2011 Apr 25; 51(4):852-64.
  4. Yeka A, Gasasira A, Mpimbaza A, Achan J, Nankabirwa J, Nsobya S, Staedke SG, Donnelly MJ, Wabwire-Mangen F, Talisuna A, Dorsey G, Kamya MR, Rosenthal PJ. Malaria in Uganda: challenges to control on the long road to elimination: I. Epidemiology and current control efforts. Acta Trop. 2012 Mar; 121(3):184-95.
  5. Hans RH, Wiid IJ, van Helden PD, Wan B, Franzblau SG, Gut J, Rosenthal PJ, Chibale K. Novel thiolactone-isatin hybrids as potential antimalarial and antitubercular agents. Bioorg Med Chem Lett. 2011 Apr 01; 21(7):2055-8.
  6. Gut J, Ang KK, Legac J, Arkin MR, Rosenthal PJ, McKerrow JH. An image-based assay for high throughput screening of Giardia lamblia. J Microbiol Methods. 2011 Mar; 84(3):398-405.
  7. Boyom FF, Fokou PV, Yamthe LR, Mfopa AN, Kemgne EM, Mbacham WF, Tsamo E, Zollo PH, Gut J, Rosenthal PJ. Potent antiplasmodial extracts from Cameroonian Annonaceae. J Ethnopharmacol. 2011 Apr 12; 134(3):717-24.
  8. Praveen Kumar S, Gut J, Guedes RC, Rosenthal PJ, Santos MM, Moreira R. Design, synthesis and evaluation of 3-methylene-substituted indolinones as antimalarials. Eur J Med Chem. 2011 Mar; 46(3):927-33.
  9. Lavrado J, Cabal GG, Prudêncio M, Mota MM, Gut J, Rosenthal PJ, Díaz C, Guedes RC, dos Santos DJ, Bichenkova E, Douglas KT, Moreira R, Paulo A. Incorporation of basic side chains into cryptolepine scaffold: structure-antimalarial activity relationships and mechanistic studies. J Med Chem. 2011 Feb 10; 54(3):734-50.
  10. Büchold C, Hemberger Y, Heindl C, Welker A, Degel B, Pfeuffer T, Staib P, Schneider S, Rosenthal PJ, Gut J, Morschhäuser J, Bringmann G, Schirmeister T. New cis-configured aziridine-2-carboxylates as aspartic acid protease inhibitors. ChemMedChem. 2011 Jan 03; 6(1):141-52.
  11. Ruel TD, Kamya MR, Li P, Pasutti W, Charlebois ED, Liegler T, Dorsey G, Rosenthal PJ, Havlir DV, Wong JK, Achan J. Early virologic failure and the development of antiretroviral drug resistance mutations in HIV-infected Ugandan children. J Acquir Immune Defic Syndr. 2011 Jan 01; 56(1):44-50.
  12. Rosenthal PJ. Falcipains and other cysteine proteases of malaria parasites. Adv Exp Med Biol. 2011; 712:30-48.
  13. Cruz LN, Alves E, Leal MT, Juliano MA, Rosenthal PJ, Juliano L, Garcia CR. FRET peptides reveal differential proteolytic activation in intraerythrocytic stages of the malaria parasites Plasmodium berghei and Plasmodium yoelii. Int J Parasitol. 2011 Mar; 41(3-4):363-72.
  14. Zhang YK, Plattner JJ, Freund YR, Easom EE, Zhou Y, Gut J, Rosenthal PJ, Waterson D, Gamo FJ, Angulo-Barturen I, Ge M, Li Z, Li L, Jian Y, Cui H, Wang H, Yang J. Synthesis and structure-activity relationships of novel benzoxaboroles as a new class of antimalarial agents. Bioorg Med Chem Lett. 2011 Jan 15; 21(2):644-51.
  15. Gama BE, de Oliveira NK, de Souza JM, Santos F, de Carvalho LJ, Melo YF, Rosenthal PJ, Daniel-Ribeiro CT, Ferreira-da-Cruz Mde F. Brazilian Plasmodium falciparum isolates: investigation of candidate polymorphisms for artemisinin resistance before introduction of artemisinin-based combination therapy. Malar J. 2010 Dec 08; 9:355.
  16. Boyom FF, Ngouana V, Kemgne EA, Zollo PH, Menut C, Bessiere JM, Gut J, Rosenthal PJ. Antiplasmodial volatile extracts from Cleistopholis patens Engler & Diels and Uvariastrum pierreanum Engl. (Engl. & Diels) (Annonaceae) growing in Cameroon. Parasitol Res. 2011 May; 108(5):1211-7.
  17. Baliraine FN, Nsobya SL, Achan J, Tibenderana JK, Talisuna AO, Greenhouse B, Rosenthal PJ. Limited ability of Plasmodium falciparum pfcrt, pfmdr1, and pfnhe1 polymorphisms to predict quinine in vitro sensitivity or clinical effectiveness in Uganda. Antimicrob Agents Chemother. 2011 Feb; 55(2):615-22.
  18. Sun L, Shah F, Helal MA, Wu Y, Pedduri Y, Chittiboyina AG, Gut J, Rosenthal PJ, Avery MA. Design, synthesis, and development of novel guaianolide-endoperoxides as potential antimalarial agents. J Med Chem. 2010 Nov 11; 53(21):7864-8.
  19. Charlebois ED, Das M, Porco TC, Havlir DV. The effect of expanded antiretroviral treatment strategies on the HIV epidemic among men who have sex with men in San Francisco. Clin Infect Dis. 2011 Apr 15; 52(8):1046-9.
  20. Guantai EM, Ncokazi K, Egan TJ, Gut J, Rosenthal PJ, Smith PJ, Chibale K. Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compounds. Bioorg Med Chem. 2010 Dec 01; 18(23):8243-56.
  21. Gibbons P, Verissimo E, Araujo NC, Barton V, Nixon GL, Amewu RK, Chadwick J, Stocks PA, Biagini GA, Srivastava A, Rosenthal PJ, Gut J, Guedes RC, Moreira R, Sharma R, Berry N, Cristiano ML, Shone AE, Ward SA, O'Neill PM. Endoperoxide carbonyl falcipain 2/3 inhibitor hybrids: toward combination chemotherapy of malaria through a single chemical entity. J Med Chem. 2010 Nov 25; 53(22):8202-6.
  22. Nankabirwa J, Cundill B, Clarke S, Kabatereine N, Rosenthal PJ, Dorsey G, Brooker S, Staedke SG. Efficacy, safety, and tolerability of three regimens for prevention of malaria: a randomized, placebo-controlled trial in Ugandan schoolchildren. PLoS One. 2010 Oct 19; 5(10):e13438.
  23. Na BK, Bae YA, Zo YG, Choe Y, Kim SH, Desai PV, Avery MA, Craik CS, Kim TS, Rosenthal PJ, Kong Y. Biochemical properties of a novel cysteine protease of Plasmodium vivax, vivapain-4. PLoS Negl Trop Dis. 2010 Oct 12; 4(10):e849.
  24. Li P, Ruel T, Fujimoto K, Hatano H, Yukl S, Eller LA, Liegler T, Kamya M, Gassasira A, Dorsey G, Rosenthal PJ, Havlir DV, Wong JK. Novel application of Locked Nucleic Acid chemistry for a Taqman assay for measuring diverse human immunodeficiency virus type 1 subtypes. J Virol Methods. 2010 Dec; 170(1-2):115-20.
  25. Coterón JM, Catterick D, Castro J, Chaparro MJ, Díaz B, Fernández E, Ferrer S, Gamo FJ, Gordo M, Gut J, de las Heras L, Legac J, Marco M, Miguel J, Muñoz V, Porras E, de la Rosa JC, Ruiz JR, Sandoval E, Ventosa P, Rosenthal PJ, Fiandor JM. Falcipain inhibitors: optimization studies of the 2-pyrimidinecarbonitrile lead series. J Med Chem. 2010 Aug 26; 53(16):6129-52.