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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- Taylor AR, Flegg JA, Nsobya SL, Yeka A, Kamya MR, Rosenthal PJ, Dorsey G, Sibley CH, Guerin PJ, Holmes CC. Estimation of malaria haplotype and genotype frequencies: a statistical approach to overcome the challenge associated with multiclonal infections. Malar J. 2014 Mar 17; 13:102.
- Raj R, Biot C, Carrère-Kremer S, Kremer L, Guérardel Y, Gut J, Rosenthal PJ, Forge D, Kumar V. 7-chloroquinoline-isatin conjugates: antimalarial, antitubercular, and cytotoxic evaluation. Chem Biol Drug Des. 2014 May; 83(5):622-9.
- Nankoberanyi S, Mbogo GW, LeClair NP, Conrad MD, Tumwebaze P, Tukwasibwe S, Kamya MR, Tappero J, Nsobya SL, Rosenthal PJ. Validation of the ligase detection reaction fluorescent microsphere assay for the detection of Plasmodium falciparum resistance mediating polymorphisms in Uganda. Malar J. 2014 Mar 14; 13:95.
- Nankabirwa JI, Wandera B, Amuge P, Kiwanuka N, Dorsey G, Rosenthal PJ, Brooker SJ, Staedke SG, Kamya MR. Impact of intermittent preventive treatment with dihydroartemisinin-piperaquine on malaria in Ugandan schoolchildren: a randomized, placebo-controlled trial. Clin Infect Dis. 2014 May; 58(10):1404-12.
- Gaynor BD, Amza A, Kadri B, Nassirou B, Lawan O, Maman L, Stoller NE, Yu SN, Chin SA, West SK, Bailey RL, Rosenthal PJ, Keenan JD, Porco TC, Lietman TM. Impact of mass azithromycin distribution on malaria parasitemia during the low-transmission season in Niger: a cluster-randomized trial. Am J Trop Med Hyg. 2014 May; 90(5):846-51.
- Conrad MD, LeClair N, Arinaitwe E, Wanzira H, Kakuru A, Bigira V, Muhindo M, Kamya MR, Tappero JW, Greenhouse B, Dorsey G, Rosenthal PJ. Comparative impacts over 5 years of artemisinin-based combination therapies on Plasmodium falciparum polymorphisms that modulate drug sensitivity in Ugandan children. J Infect Dis. 2014 Aug 01; 210(3):344-53.
- Weldon DJ, Shah F, Chittiboyina AG, Sheri A, Chada RR, Gut J, Rosenthal PJ, Shivakumar D, Sherman W, Desai P, Jung JC, Avery MA. Synthesis, biological evaluation, hydration site thermodynamics, and chemical reactivity analysis of α-keto substituted peptidomimetics for the inhibition of Plasmodium falciparum. Bioorg Med Chem Lett. 2014 Mar 01; 24(5):1274-9.
- Tukwasibwe S, Mugenyi L, Mbogo GW, Nankoberanyi S, Maiteki-Sebuguzi C, Joloba ML, Nsobya SL, Staedke SG, Rosenthal PJ. Differential prevalence of transporter polymorphisms in symptomatic and asymptomatic falciparum malaria infections in Uganda. J Infect Dis. 2014 Jul 01; 210(1):154-7.
- Raj R, Gut J, Rosenthal PJ, Kumar V. 1H-1,2,3-Triazole-tethered isatin-7-chloroquinoline and 3-hydroxy-indole-7-chloroquinoline conjugates: synthesis and antimalarial evaluation. Bioorg Med Chem Lett. 2014 Feb 01; 24(3):756-9.
- Rosenthal PJ. Changes at our journal. Am J Trop Med Hyg. 2014 Jan; 90(1):1-2.
- Kjellin LL, Dorsey G, Rosenthal PJ, Aweeka F, Huang L. Determination of the antimalarial drug piperaquine in small volume pediatric plasma samples by LC-MS/MS. Bioanalysis. 2014; 6(23):3081-9.
- Miranda D, Capela R, Albuquerque IS, Meireles P, Paiva I, Nogueira F, Amewu R, Gut J, Rosenthal PJ, Oliveira R, Mota MM, Moreira R, Marti F, Prudêncio M, O'Neill PM, Lopes F. Novel endoperoxide-based transmission-blocking antimalarials with liver- and blood-schizontocidal activities. ACS Med Chem Lett. 2014 Feb 13; 5(2):108-12.
- Singh P, Raj R, Singh P, Gut J, Rosenthal PJ, Kumar V. Urea/oxalamide tethered β-lactam-7-chloroquinoline conjugates: synthesis and in vitro antimalarial evaluation. Eur J Med Chem. 2014 Jan; 71:128-34.
- Raj R, Biot C, Carrère-Kremer S, Kremer L, Guérardel Y, Gut J, Rosenthal PJ, Kumar V. 4-Aminoquinoline-β-lactam conjugates: synthesis, antimalarial, and antitubercular evaluation. Chem Biol Drug Des. 2014 Feb; 83(2):191-7.
- Mugumbate G, Newton AS, Rosenthal PJ, Gut J, Moreira R, Chibale K, Guedes RC. Novel anti-plasmodial hits identified by virtual screening of the ZINC database. J Comput Aided Mol Des. 2013 Oct; 27(10):859-71.
- Tukulula M, Njoroge M, Abay ET, Mugumbate GC, Wiesner L, Taylor D, Gibhard L, Norman J, Swart KJ, Gut J, Rosenthal PJ, Barteau S, Streckfuss J, Kameni-Tcheudji J, Chibale K. Synthesis and in vitro and in vivo pharmacological evaluation of new 4-aminoquinoline-based compounds. ACS Med Chem Lett. 2013 Dec 12; 4(12):1198-202.
- Ressurreição AS, Gonçalves D, Sitoe AR, Albuquerque IS, Gut J, Góis A, Gonçalves LM, Bronze MR, Hanscheid T, Biagini GA, Rosenthal PJ, Prudêncio M, O'Neill P, Mota MM, Lopes F, Moreira R. Structural optimization of quinolon-4(1H)-imines as dual-stage antimalarials: toward increased potency and metabolic stability. J Med Chem. 2013 Oct 10; 56(19):7679-90.
- Rodrigues T, Ressurreição AS, da Cruz FP, Albuquerque IS, Gut J, Carrasco MP, Gonçalves D, Guedes RC, dos Santos DJ, Mota MM, Rosenthal PJ, Moreira R, Prudêncio M, Lopes F. Flavones as isosteres of 4(1H)-quinolones: discovery of ligand efficient and dual stage antimalarial lead compounds. Eur J Med Chem. 2013 Nov; 69:872-80.
- Ribeiro CJ, Kumar SP, Gut J, Gonçalves LM, Rosenthal PJ, Moreira R, Santos MM. Squaric acid/4-aminoquinoline conjugates: novel potent antiplasmodial agents. Eur J Med Chem. 2013 Nov; 69:365-72.
- Gong L, Parikh S, Rosenthal PJ, Greenhouse B. Biochemical and immunological mechanisms by which sickle cell trait protects against malaria. Malar J. 2013 Sep 11; 12:317.
- Prasad R, Atul , Kolla VK, Legac J, Singhal N, Navale R, Rosenthal PJ, Sijwali PS. Blocking Plasmodium falciparum development via dual inhibition of hemoglobin degradation and the ubiquitin proteasome system by MG132. PLoS One. 2013; 8(9):e73530.
- Rosenthal PJ. The interplay between drug resistance and fitness in malaria parasites. Mol Microbiol. 2013 Sep; 89(6):1025-38.
- Mba'ning BM, Lenta BN, Noungoué DT, Antheaume C, Fongang YF, Ngouela SA, Boyom FF, Rosenthal PJ, Tsamo E, Sewald N, Laatsch H. Antiplasmodial sesquiterpenes from the seeds of Salacia longipes var. camerunensis. Phytochemistry. 2013 Dec; 96:347-52.
- Oliveira R, Newton AS, Guedes RC, Miranda D, Amewu RK, Srivastava A, Gut J, Rosenthal PJ, O'Neill PM, Ward SA, Lopes F, Moreira R. An endoperoxide-based hybrid approach to deliver falcipain inhibitors inside malaria parasites. ChemMedChem. 2013 Sep; 8(9):1528-36.
- Tukulula M, Njoroge M, Mugumbate GC, Gut J, Rosenthal PJ, Barteau S, Streckfuss J, Heudi O, Kameni-Tcheudji J, Chibale K. Tetrazole-based deoxyamodiaquines: synthesis, ADME/PK profiling and pharmacological evaluation as potential antimalarial agents. Bioorg Med Chem. 2013 Sep 01; 21(17):4904-13.