Dr. John White

John White is a senior research scientist working in the malaria field for over 20 years. He received his Ph.D from the University of Washington (Pathobiology) based on his work developing high throughput in vitro methodologies that measure the capacity of Plasmodium falciparum strains to acquire drug resistance. Currently, Dr. White is making advances in our understanding of genetic plasticity among natural P. falciparum isolates of India as key personnel to the NIH-funded South Asia International Center of Excellence for Malaria Research.

Email: jwhite3@uw.edu

Publications

Kokkonda, S, El Mazouni, F, White, KL, White, J, Shackleford, DM, Lafuente-Monasterio, MJ et al.. Isoxazolopyrimidine-Based Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase with Antimalarial Activity. ACS Omega. 2018;3 (8):9227-9240. doi: 10.1021/acsomega.8b01573. PubMed PMID:30197997 PubMed Central PMC6120730.

White, J, Rathod, PK. Indispensable malaria genes. Science. 2018;360 (6388):490-491. doi: 10.1126/science.aat5092. PubMed PMID:29724941 .

Phillips, MA, White, KL, Kokkonda, S, Deng, X, White, J, El Mazouni, F et al.. A Triazolopyrimidine-Based Dihydroorotate Dehydrogenase Inhibitor with Improved Drug-like Properties for Treatment and Prevention of Malaria. ACS Infect Dis. 2016;2 (12):945-957. doi: 10.1021/acsinfecdis.6b00144. PubMed PMID:27641613 PubMed Central PMC5148661.

White, J, Mascarenhas, A, Pereira, L, Dash, R, Walke, JT, Gawas, P et al.. In vitro adaptation of Plasmodium falciparum reveal variations in cultivability. Malar. J. 2016;15 :33. doi: 10.1186/s12936-015-1053-0. PubMed PMID:26794408 PubMed Central PMC4722725.

Phillips, MA, Lotharius, J, Marsh, K, White, J, Dayan, A, White, KL et al.. A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria. Sci Transl Med. 2015;7 (296):296ra111. doi: 10.1126/scitranslmed.aaa6645. PubMed PMID:26180101 PubMed Central PMC4539048.

Mudeppa, DG, Kumar, S, Kokkonda, S, White, J, Rathod, PK. Topoisomerase II from Human Malaria Parasites: EXPRESSION, PURIFICATION, AND SELECTIVE INHIBITION. J. Biol. Chem. 2015;290 (33):20313-24. doi: 10.1074/jbc.M115.639039. PubMed PMID:26055707 PubMed Central PMC4536438.

Guler, JL, White, J 3rd, Phillips, MA, Rathod, PK. Atovaquone tolerance in Plasmodium falciparum parasites selected for high-level resistance to a dihydroorotate dehydrogenase inhibitor. Antimicrob. Agents Chemother. 2015;59 (1):686-9. doi: 10.1128/AAC.02347-14. PubMed PMID:25331708 PubMed Central PMC4291421.

Deng, X, Kokkonda, S, El Mazouni, F, White, J, Burrows, JN, Kaminsky, W et al.. Fluorine modulates species selectivity in the triazolopyrimidine class of Plasmodium falciparum dihydroorotate dehydrogenase inhibitors. J. Med. Chem. 2014;57 (12):5381-94. doi: 10.1021/jm500481t. PubMed PMID:24801997 PubMed Central PMC4079327.

Guler, JL, Freeman, DL, Ahyong, V, Patrapuvich, R, White, J, Gujjar, R et al.. Asexual populations of the human malaria parasite, Plasmodium falciparum, use a two-step genomic strategy to acquire accurate, beneficial DNA amplifications. PLoS Pathog. 2013;9 (5):e1003375. doi: 10.1371/journal.ppat.1003375. PubMed PMID:23717205 PubMed Central PMC3662640.

Marwaha, A, White, J, El Mazouni, F, Creason, SA, Kokkonda, S, Buckner, FS et al.. Bioisosteric transformations and permutations in the triazolopyrimidine scaffold to identify the minimum pharmacophore required for inhibitory activity against Plasmodium falciparum dihydroorotate dehydrogenase. J. Med. Chem. 2012;55 (17):7425-36. doi: 10.1021/jm300351w. PubMed PMID:22877245 PubMed Central PMC3446820.

Coteron, JM, Marco, M, Esquivias, J, Deng, X, White, KL, White, J et al.. Structure-guided lead optimization of triazolopyrimidine-ring substituents identifies potent Plasmodium falciparum dihydroorotate dehydrogenase inhibitors with clinical candidate potential. J. Med. Chem. 2011;54 (15):5540-61. doi: 10.1021/jm200592f. PubMed PMID:21696174 PubMed Central PMC3156099.

Gujjar, R, El Mazouni, F, White, KL, White, J, Creason, S, Shackleford, DM et al.. Lead optimization of aryl and aralkyl amine-based triazolopyrimidine inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with antimalarial activity in mice. J. Med. Chem. 2011;54 (11):3935-49. doi: 10.1021/jm200265b. PubMed PMID:21517059 PubMed Central PMC3124361.

Gujjar, R, Marwaha, A, El Mazouni, F, White, J, White, KL, Creason, S et al.. Identification of a metabolically stable triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity in mice. J. Med. Chem. 2009;52 (7):1864-72. doi: 10.1021/jm801343r. PubMed PMID:19296651 PubMed Central PMC2746568.

Ganesan, K, Ponmee, N, Jiang, L, Fowble, JW, White, J, Kamchonwongpaisan, S et al.. A genetically hard-wired metabolic transcriptome in Plasmodium falciparum fails to mount protective responses to lethal antifolates. PLoS Pathog. 2008;4 (11):e1000214. doi: 10.1371/journal.ppat.1000214. PubMed PMID:19023412 PubMed Central PMC2581438.

Phillips, MA, Gujjar, R, Malmquist, NA, White, J, El Mazouni, F, Baldwin, J et al.. Triazolopyrimidine-based dihydroorotate dehydrogenase inhibitors with potent and selective activity against the malaria parasite Plasmodium falciparum. J. Med. Chem. 2008;51 (12):3649-53. doi: 10.1021/jm8001026. PubMed PMID:18522386 PubMed Central PMC2624570.

Eastman, RT, White, J, Hucke, O, Yokoyama, K, Verlinde, CL, Hast, MA et al.. Resistance mutations at the lipid substrate binding site of Plasmodium falciparum protein farnesyltransferase. Mol. Biochem. Parasitol. 2007;152 (1):66-71. doi: 10.1016/j.molbiopara.2006.11.012. PubMed PMID:17208314 PubMed Central PMC2875941.

Pang, CK, De, SK, White, J, Buckner, FS, Varani, G, Rathod, PK et al.. Differential drug binding by the highly conserved Plasmodium falciparum thymidylate synthase. Mol. Biochem. Parasitol. 2005;143 (1):121-4. doi: 10.1016/j.molbiopara.2005.02.016. PubMed PMID:15978681 .

Baldwin, J, Michnoff, CH, Malmquist, NA, White, J, Roth, MG, Rathod, PK et al.. High-throughput screening for potent and selective inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase. J. Biol. Chem. 2005;280 (23):21847-53. doi: 10.1074/jbc.M501100200. PubMed PMID:15795226 .

Eastman, RT, White, J, Hucke, O, Bauer, K, Yokoyama, K, Nallan, L et al.. Resistance to a protein farnesyltransferase inhibitor in Plasmodium falciparum. J. Biol. Chem. 2005;280 (14):13554-9. doi: 10.1074/jbc.M413556200. PubMed PMID:15661734 .

Shelby, JP, White, J, Ganesan, K, Rathod, PK, Chiu, DT. A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum-infected erythrocytes. Proc. Natl. Acad. Sci. U.S.A. 2003;100 (25):14618-22. doi: 10.1073/pnas.2433968100. PubMed PMID:14638939 PubMed Central PMC299747.

Jiang, L, Lee, PC, White, J, Rathod, PK. Potent and selective activity of a combination of thymidine and 1843U89, a folate-based thymidylate synthase inhibitor, against Plasmodium falciparum. Antimicrob. Agents Chemother. 2000;44 (4):1047-50. . PubMed PMID:10722510 PubMed Central PMC89811.