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. Lopes EA, Mestre R, Fontinha D, Legac J, Pei JV, Sanches-Vaz M, Mori M, Lehane AM, Rosenthal PJ, Prudêncio M, Santos MMM. Discovery of spirooxadiazoline oxindoles with dual-stage antimalarial activity. Eur J Med Chem. 2022 Jun 05; 236:114324.
  2. Perrillo R, Lin HS, Schwarz KB, Rosenthal P, Lisker-Melman M, Chung RT, Prokunina-Olsson L, Cloherty G, Feld J, Hepatitis B Research Network (HBRN). Changes in serum hepatitis B surface and e antigen, interferon-inducible protein 10, and aminotransferase levels during combination therapy of immune-tolerant chronic hepatitis B. Hepatology. 2022 09; 76(3):775-787.
  3. Huang L, Sok V, Aslam-Mir U, Marzan F, Whalen M, Rosenthal PJ, Aweeka F. Determination of unbound piperaquine in human plasma by ultra-high performance liquid chromatography tandem mass spectrometry. J Chromatogr Open. 2022 Nov; 2.
  4. Okitwi M, Orena S, Thomas K, Tumwebaze PK, Byaruhanga O, Nsobya SL, Conrad MD, Bayles BR, Rosenthal PJ, Cooper RA. Impact of Short-Term Storage on Ex Vivo Antimalarial Susceptibilities of Fresh Ugandan Plasmodium falciparum Isolates. Antimicrob Agents Chemother. 2022 04 19; 66(4):e0143721.
  5. Brinkmann S, Semmler S, Kersten C, Patras MA, Kurz M, Fuchs N, Hammerschmidt SJ, Legac J, Hammann PE, Vilcinskas A, Rosenthal PJ, Schirmeister T, Bauer A, Schäberle TF. Identification, Characterization, and Synthesis of Natural Parasitic Cysteine Protease Inhibitors: Pentacitidins Are More Potent Falcitidin Analogues. ACS Chem Biol. 2022 03 18; 17(3):576-589.
  6. Nachega JB, Sam-Agudu NA, Machekano RN, Rabie H, van der Zalm MM, Redfern A, Dramowski A, O'Connell N, Pipo MT, Tshilanda MB, Byamungu LN, Masekela R, Jeena PM, Pillay A, Gachuno OW, Kinuthia J, Ishoso DK, Amoako E, Agyare E, Agbeno EK, Martyn-Dickens C, Sylverken J, Enimil A, Jibril AM, Abdullahi AM, Amadi O, Umar UM, Sigwadhi LN, Hermans MP, Otokoye JO, Mbala-Kingebeni P, Muyembe-Tamfum JJ, Zumla A, Sewankambo NK, Aanyu HT, Musoke P, Suleman F, Adejumo P, Noormahomed EV, Deckelbaum RJ, Fowler MG, Tshilolo L, Smith G, Mills EJ, Umar LW, Siedner MJ, Kruger M, Rosenthal PJ, Mellors JW, Mofenson LM, African Forum for Research and Education in Health (AFREhealth) COVID-19 Research Collaboration on C. Assessment of Clinical Outcomes Among Children and Adolescents Hospitalized With COVID-19 in 6 Sub-Saharan African Countries. JAMA Pediatr. 2022 Mar 01; 176(3):e216436.
  7. Taft BR, Yokokawa F, Kirrane T, Mata AC, Huang R, Blaquiere N, Waldron G, Zou B, Simon O, Vankadara S, Chan WL, Ding M, Sim S, Straimer J, Guiguemde A, Lakshminarayana SB, Jain JP, Bodenreider C, Thompson C, Lanshoeft C, Shu W, Fang E, Qumber J, Chan K, Pei L, Chen YL, Schulz H, Lim J, Abas SN, Ang X, Liu Y, Angulo-Barturen I, Jiménez-Díaz MB, Gamo FJ, Crespo-Fernandez B, Rosenthal PJ, Cooper RA, Tumwebaze P, Aguiar ACC, Campo B, Campbell S, Wagner J, Diagana TT, Sarko C. Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria. J Med Chem. 2022 03 10; 65(5):3798-3813.
  8. Kreutzfeld O, Tumwebaze PK, Byaruhanga O, Katairo T, Okitwi M, Orena S, Rasmussen SA, Legac J, Conrad MD, Nsobya SL, Aydemir O, Bailey JA, Duffey M, Cooper RA, Rosenthal PJ. Decreased susceptibility to dihydrofolate reductase inhibitors associated with genetic polymorphisms in Ugandan Plasmodium falciparum isolates. J Infect Dis. 2021 Aug 30.
  9. Fidock DA, Rosenthal PJ. Artemisinin resistance in Africa: How urgent is the threat? Med (N Y). 2021 12 10; 2(12):1287-1288.
  10. Wallender E, Ali AM, Hughes E, Kakuru A, Jagannathan P, Muhindo MK, Opira B, Whalen M, Huang L, Duvalsaint M, Legac J, Kamya MR, Dorsey G, Aweeka F, Rosenthal PJ, Savic RM. Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children. Nat Commun. 2021 11 18; 12(1):6714.
  11. Kanai M, Yeo T, Asua V, Rosenthal PJ, Fidock DA, Mok S. Comparative Analysis of Plasmodium falciparum Genotyping via SNP Detection, Microsatellite Profiling, and Whole-Genome Sequencing. Antimicrob Agents Chemother. 2022 01 18; 66(1):e0116321.
  12. Rosenthal PJ. Are Artemisinin-Based Combination Therapies For Malaria Beginning To Fail in Africa? Am J Trop Med Hyg. 2021 Sep 07.
  13. Kreutzfeld O, Rasmussen SA, Ramanathan AA, Tumwebaze PK, Byaruhanga O, Katairo T, Asua V, Okitwi M, Orena S, Legac J, Conrad MD, Nsobya SL, Aydemir O, Bailey J, Duffey M, Bayles BR, Vaidya AB, Cooper RA, Rosenthal PJ. Associations between Varied Susceptibilities to PfATP4 Inhibitors and Genotypes in Ugandan Plasmodium falciparum Isolates. Antimicrob Agents Chemother. 2021 09 17; 65(10):e0077121.
  14. Murithi JM, Pascal C, Bath J, Boulenc X, Gnädig NF, Pasaje CFA, Rubiano K, Yeo T, Mok S, Klieber S, Desert P, Jiménez-Díaz MB, Marfurt J, Rouillier M, Cherkaoui-Rbati MH, Gobeau N, Wittlin S, Uhlemann AC, Price RN, Wirjanata G, Noviyanti R, Tumwebaze P, Cooper RA, Rosenthal PJ, Sanz LM, Gamo FJ, Joseph J, Singh S, Bashyam S, Augereau JM, Giraud E, Bozec T, Vermat T, Tuffal G, Guillon JM, Menegotto J, Sallé L, Louit G, Cabanis MJ, Nicolas MF, Doubovetzky M, Merino R, Bessila N, Angulo-Barturen I, Baud D, Bebrevska L, Escudié F, Niles JC, Blasco B, Campbell S, Courtemanche G, Fraisse L, Pellet A, Fidock DA, Leroy D. The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to Plasmodium falciparum parasite resistance. Sci Transl Med. 2021 07 21; 13(603).
  15. Stokes BH, Dhingra SK, Rubiano K, Mok S, Straimer J, Gnädig NF, Deni I, Schindler KA, Bath JR, Ward KE, Striepen J, Yeo T, Ross LS, Legrand E, Ariey F, Cunningham CH, Souleymane IM, Gansané A, Nzoumbou-Boko R, Ndayikunda C, Kabanywanyi AM, Uwimana A, Smith SJ, Kolley O, Ndounga M, Warsame M, Leang R, Nosten F, Anderson TJ, Rosenthal PJ, Ménard D, Fidock DA. Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness. Elife. 2021 07 19; 10.
  16. Duvalsaint M, Conrad MD, Tukwasibwe S, Tumwebaze PK, Legac J, Cooper RA, Rosenthal PJ. Balanced impacts of fitness and drug pressure on the evolution of PfMDR1 polymorphisms in Plasmodium falciparum. Malar J. 2021 Jun 30; 20(1):292.
  17. Ekusai-Sebatta D, Arinaitwe E, Mpimbaza A, Nankabirwa JI, Drakeley C, Rosenthal PJ, Staedke SG, Muyinda H. Challenges and opportunities for use of long-lasting insecticidal nets to prevent malaria during overnight travel in Uganda: a qualitative study. Malar J. 2021 Jun 26; 20(1):283.
  18. Tumwebaze PK, Katairo T, Okitwi M, Byaruhanga O, Orena S, Asua V, Duvalsaint M, Legac J, Chelebieva S, Ceja FG, Rasmussen SA, Conrad MD, Nsobya SL, Aydemir O, Bailey JA, Bayles BR, Rosenthal PJ, Cooper RA. Drug susceptibility of Plasmodium falciparum in eastern Uganda: a longitudinal phenotypic and genotypic study. Lancet Microbe. 2021 09; 2(9):e441-e449.
  19. Andolina C, Rek JC, Briggs J, Okoth J, Musiime A, Ramjith J, Teyssier N, Conrad M, Nankabirwa JI, Lanke K, Rodriguez-Barraquer I, Meerstein-Kessel L, Arinaitwe E, Olwoch P, Rosenthal PJ, Kamya MR, Dorsey G, Greenhouse B, Drakeley C, Staedke SG, Bousema T. Sources of persistent malaria transmission in a setting with effective malaria control in eastern Uganda: a longitudinal, observational cohort study. Lancet Infect Dis. 2021 Jun 16.
  20. Pal K, Raza MK, Legac J, Ataur Rahman M, Manzoor S, Rosenthal PJ, Hoda N. Design, synthesis, crystal structure and anti-plasmodial evaluation of tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives. RSC Med Chem. 2021 Jun 23; 12(6):970-981.
  21. Palmer MJ, Deng X, Watts S, Krilov G, Gerasyuto A, Kokkonda S, El Mazouni F, White J, White KL, Striepen J, Bath J, Schindler KA, Yeo T, Shackleford DM, Mok S, Deni I, Lawong A, Huang A, Chen G, Wang W, Jayaseelan J, Katneni K, Patil R, Saunders J, Shahi SP, Chittimalla R, Angulo-Barturen I, Jiménez-Díaz MB, Wittlin S, Tumwebaze PK, Rosenthal PJ, Cooper RA, Aguiar ACC, Guido RVC, Pereira DB, Mittal N, Winzeler EA, Tomchick DR, Laleu B, Burrows JN, Rathod PK, Fidock DA, Charman SA, Phillips MA. Potent Antimalarials with Development Potential Identified by Structure-Guided Computational Optimization of a Pyrrole-Based Dihydroorotate Dehydrogenase Inhibitor Series. J Med Chem. 2021 05 13; 64(9):6085-6136.
  22. Rani A, Sharma A, Legac J, Rosenthal PJ, Singh P, Kumar V. A trio of quinoline-isoniazid-phthalimide with promising antiplasmodial potential: Synthesis, in-vitro evaluation and heme-polymerization inhibition studies. Bioorg Med Chem. 2021 06 01; 39:116159.
  23. Rosenthal PJ. Has artemisinin resistance emerged in Africa? Lancet Infect Dis. 2021 08; 21(8):1056-1057.
  24. Asua V, Conrad MD, Aydemir O, Duvalsaint M, Legac J, Duarte E, Tumwebaze P, Chin DM, Cooper RA, Yeka A, Kamya MR, Dorsey G, Nsobya SL, Bailey J, Rosenthal PJ. Changing Prevalence of Potential Mediators of Aminoquinoline, Antifolate, and Artemisinin Resistance Across Uganda. J Infect Dis. 2021 Mar 29; 223(6):985-994.
  25. Zhan W, Zhang H, Ginn J, Leung A, Liu YJ, Michino M, Toita A, Okamoto R, Wong TT, Imaeda T, Hara R, Yukawa T, Chelebieva S, Tumwebaze PK, Lafuente-Monasterio MJ, Martinez-Martinez MS, Vendome J, Beuming T, Sato K, Aso K, Rosenthal PJ, Cooper RA, Meinke PT, Nathan CF, Kirkman LA, Lin G. Development of a Highly Selective Plasmodium falciparum Proteasome Inhibitor with Anti-malaria Activity in Humanized Mice. Angew Chem Int Ed Engl. 2021 04 19; 60(17):9279-9283.