David A. Fidock, Ph.D.
C.S. Hamish Young Professor of Microbiology & Immunology and Medical Sciences (in Medicine)
Ph.D., Pasteur Institute Paris
Malaria drug resistance, chemotherapy, pathogenesis, fatty acid metabolism, cell development
Research
Biological investigations into Plasmodium falciparum, the etiologic agent of severe malaria, reveal an organism that is tremendously adept at overcoming therapeutic attack and evading host immunity. This haploid apicomplexan parasite causes disease in over half a billion individuals and kills over a million African children yearly, and prevents sterilizing immunity from being acquired even by individuals who have been infected thousands of times. Disease can result from severe anemia, hyperparasitemia, or other complications resulting from sequestration of parasitized red blood cells (RBC) in the microvasculature, a process that depends on the presentation of antigenically distinct parasite proteins on the infected RBC surface. Chemotherapeutic clearance of asexual blood stage parasites is the linchpin of malaria treatment and control, however it is systematically thwarted by the acquisition of resistance. The most dramatic consequence has been with chloroquine (CQ), for decades the gold standard until resistance appeared and pre-empted a dramatic increase in malaria mortality and morbidity rates, particularly in Africa.
During my past 30 years of malaria research, I have investigated how P. falciparum invades and develops within hepatocytes and RBC, what immune effector mechanisms operate on these stages, how antimalarials act and how parasites counter their action, and how parasites are successfully transmitted to Anopheles mosquitoes, their definitive host. My laboratory's ongoing and planned research channels these interests into several themes:
1) What are the parasite factors that mediate resistance to antimalarial drugs;
2) What biological processes are targeted by antimalarial drugs and what accounts for parasite death;
3) What biochemical and physiological functions are intrinsic to the digestive vacuole (DV) and the apicoplast, the site of action of CQ and of antibiotics respectively; and
4) How does P. falciparum regulate its virulence and prevent the establishment of protective immunity.
These studies benefit from our extensive experience in P. falciparum transfection and we constantly strive for new innovations in genetics to enhance the power of these investigations.
Please see our lab website as well as my publications on PubMed and Google Scholar for more information about our research and publications.
Professor Fidock is a Fellow of the American Academy of Microbiology and the American Society of Tropical Medicine and Hygiene (ASTMH). He is the incoming President of the ASTMH.
Selected Publications
Ishengoma, D.S., Gosling, R., Martinez-Vega, R., Beshir, K.B., Bailey, J.A., Chimumbwa, J., Sutherland, C., Conrad, M.D., Tadesse, F.G., Juliano, J.J., Kamya, M.R., Mbacham, W.F., Ménard, D., Rosenthal, P.J., Raman, J., Tatarsky, A., Tessema, SK., Fidock, D.A. and Djimde, A.A. (2024) Urgent action is needed to confront artemisinin partial resistance in African malaria parasites. Nature Med. 7: 1807-1808. PMID: 38710833.
Small-Saunders, J.L., Sinha, A., Bloxham, T.S., Hagenah, L.M., Sun, G., Preiser, P.R., Dedon, P.C. and Fidock, D.A. (2024) tRNA modification reprogramming contributes to artemisinin resistance in Plasmodium falciparum. Nature Microbiol. 6: 1483-1498. PMC11153160.
Rosenthal, P.J., Asua, V., Bailey, J.A., Conrad, M.D., Ishengoma, D.S., Kamya, M.R., Rasmussen, C., Tadesse, F.G., Uwimana, A. and Fidock, D.A. (2024) The emergence of artemisinin partial resistance in Africa: how do we respond? Lancet Infect. Dis. 26: S1473-3099(24)00141-5. Epub ahead of print. PMID: 38552654.
Mok, S. and Fidock, D.A. (2024). Determinants of piperaquine-resistant malaria in South America. Lancet Infect. Dis. 24: 114-116. PMC10872569.
Mok, S., Yeo, T., Hong, D., Shears, M.J., Ross, L.S., Ward, K.E., Dhingra, S.K., Kanai, M., Bridgford, J.L., Tripathi, A.K., Mlambo, G., Burkhard, A.Y., Ansbro, M.R., Fairhurst, K.J., Gil-Iturbe, E., Park, H., Rozenberg, F.D., Kim, J., Mancia, F., Fairhurst, R.M., Quick, M., Uhlemann, A.C., Sinnis, P. and Fidock, D.A. (2023) Mapping the genomic landscape of multidrug resistance in Plasmodium falciparum and its impact on parasite fitness. Science Adv. 9: eadi2364. PMC10631731.
Mihreteab, S., Platon, L., Berhane, A., Stokes, B.H., Warsame, M., Campagne, P., Criscuolo, A., Ma, L., Petiot, N., Doderer-Lang, C., Legrand, E., Ward, K.E., Zehaie Kassahun, A., Ringwald, P., Fidock, D.A. and Ménard, D. (2023). Increasing prevalence of Artemisinin-resistant HRP2-negative malaria in Eritrea. N. Engl. J. Med. 389: 1191-1202. PMC10539021.
Deni, I., Stokes, B.H., Ward, K.E., Fairhurst, K.J., Pasaje, C.F.A., Yeo, T., Akbar, S., Park, H., Muir, R., Bick, D.S., Zhan, W., Zhang, H., Liu, Y.J., Ng, C.L., Kirkman, L.A., Almaliti, J., Gould, A.E., Duffey, M., O'Donoghue, A.J., Uhlemann, A.C., Niles, J.C., da Fonseca, P.C.A., Gerwick, W.H., Lin, G., Bogyo, M. and Fidock, D.A. (2023). Mitigating the risk of antimalarial resistance via covalent dual-subunit inhibition of the Plasmodium proteasome. Cell Chem. Biol. 30: 470-85.e6. PMC10198959.
Okombo, J., Mok, S., Qahash, T., Yeo, T., Bath, J., Orchard, L.M., Owens, E., Koo, I., Albert, I., Llinas, M. and Fidock, D.A. (2022). Piperaquine-resistant PfCRT mutations differentially impact drug transport, hemoglobin catabolism and parasite physiology in Plasmodium falciparum asexual blood stages. PLoS Pathog. 18: e1010926. PMC9645663.
Arendse, L.B., Murithi, J.M., Qahash, T., Pasaje, C.F.A., Godoy, L.C., Dey, S., Gibhard, L., Ghidelli-Disse, S., Drewes, G., Bantscheff, M., Lafuente-Monasterio, M.J., Fienberg, S., Wambua, L., Gachuhi, S., Coertzen, D., van der Watt, M., Reader, J., Aswat, A.S., Erlank, E., Venter, N., Mittal, N., Luth, M.R., Ottilie, S., Winzeler, E.A., Koekemoer, L.L., Birkholtz, L.M., Niles, J.C., Llinas, M., Fidock, D.A. and Chibale, K. (2022). The anticancer human mTOR inhibitor sapanisertib potently inhibits multiple Plasmodium kinases and life cycle stages. Sci. Transl. Med. 14: eabo7219. PMC9951552.
Wicht, K.J., Small-Saunders J.L., Hagenah, L.M., Mok, S. and Fidock, D.A. (2022) Mutant PfCRT can mediate piperaquine resistance in African Plasmodium falciparum with reduced fitness and increased susceptibility to other antimalarials. J. Infect. Dis. 226: 2021-2029. PMC9704436.
Okombo, J., Mok, S., Qahash, T., Yeo, T., Bath, J., Orchard, L.M., Owens, E., Koo, I., Albert, I., Llinás, M. and Fidock D.A. (2022) Piperaquine-resistant PfCRT mutations differentially impact drug transport, hemoglobin catabolism and parasite physiology in Plasmodium falciparum asexual blood stages. PLoS Pathog. 8: e1010926. PMC9645663.
Arendse, L.B., Murithi, J.M., Qahash, T., Pasaje, C.F.A., Godoy, L.C., Dey, S., Gibhard, L., Ghidelli-Disse, S., Drewes, G., Bantscheff, M., Lafuente-Monasterio, M.J., Fienberg, S., Wambua, L., Gachuhi, S., Coertzen, D., van der Watt. M., Reader, J., Aswat, A.S., Erlank, E., Venter, N., Mittal, N., Luth, M.R., Ottilie, S., Winzeler, E.A., Koekemoer, L.L., Birkholtz, L.M., Niles, J.C., Llinás, M., Fidock, D.A. and Chibale, K. (2022) The anticancer human mTOR inhibitor sapanisertib potently inhibits multiple Plasmodium kinases and life cycle stages. Sci. Transl. Med. 14: eabo7219. PMC9951552.
Stokes, B,H., Ward, K.E. and Fidock, D.A. (2022) Evidence of artemisinin-resistant malaria in Africa. N. Engl. J. Med. 386: 1385-1386. PMC9888016.
Sinnis, P. and Fidock, D.A. (2022) The RTS,S vaccine-a chance to regain the upper hand against malaria? Cell 185: 750-754. PMID: 35245476.
Small-Saunders, J.L., Hagenah, L.M., Wicht, K.J., Dhingra, S.K., Deni, I., Kim, J., Vendome, J., Gil-Iturbe, E., Roepe, P.D., Mehta, M., Mancia, F., Quick, M., Eppstein, M.J. and Fidock, D.A. (2022) Evidence for the early emergence of piperaquine-resistant Plasmodium falciparum malaria and modeling strategies to mitigate resistance. PLoS Pathog. 18: e1010278. PMC8853508.
Murithi, J.M., Deni, I., Pasaje, C.F.A., Okombo, J., Bridgford, J.L., Gnadig, N.F., Edwards, R.L., Yeo, T., Mok, S., Burkhard, A.Y., Coburn-Flynn, O., Istvan, E.S., Sakata-Kato, T., Gomez-Lorenzo, M.G., Cowell, A.N., Wicht, K.J., Le Manach, C., Kalantarov, G.F., Dey, S., Duffey, M., Laleu, B., Lukens, A.K., Ottilie, S., Vanaerschot, M., Trakht, I.N., Gamo, F.J., Wirth, D.F., Goldberg, D.E., Odom John, A.R., Chibale, K., Winzeler, E.A., Niles, J.C. and Fidock, D.A. (2022) The Plasmodium falciparum ABC transporter ABCI3 confers parasite strain-dependent pleiotropic antimalarial drug resistance. Cell Chem. Biol. 29: 824-39. PMC8727639.
McCarthy, J.S., Yalkinoglu, Ö., Odedra, A., Webster, R., Oeuvray, C., Tappert, A., Bezuidenhout, D., Giddins, M.J., Dhingra, S.K., Fidock, D.A., Marquart, L., Webb, L., Yin, X., Khandelwal, A. and Bagchus, W.M. (2021) Safety, pharmacokinetics, and antimalarial activity of the novel plasmodium eukaryotic translation elongation factor 2 inhibitor M5717: a first-in-human, randomized, placebo-controlled, double-blind, single ascending dose study and volunteer infection study. Lancet Infect. Dis. 21: 1713-1724. PMC8612936.
Thathy, V. and Fidock, D.A. (2021) Malaria parasite beats the heat. Nature Microbiol. 6: 1105-1107. PMID: 34400834.
Fidock, D.A. and Rosenthal, P.J. (2021) Artemisinin resistance in Africa: How urgent is the threat? Med.2: 1287-8. PMC8729812.
Murithi, J.M., Pascal, C., Bath, J., Boulenc, X., Gnädig, N.F., Pasaje, C.F.A., Rubiano, K., Yeo, T., Mok, S., Klieber, S., Desert, P., Jiménez-Díaz, M.B., Marfurt, J., Rouillier, M., Cherkaoui-Rbati, M.H., Gobeau, N., Wittlin, S., Uhlemann, A.C., Price, R.N., Wirjanata, G., Noviyanti, R., Tumwebaze, P., Cooper, R.A., Rosenthal, P.J., Sanz, L.M., Gamo, F.J., Joseph, J., Singh, S., Bashyam, S., Augereau, J.M., Giraud, E., Bozec, T., Vermat, T., Tuffal, G., Guillon, J.M., Menegotto, J., Sallé, L., Louit, G., Cabanis, M.J., Nicolas, M.F., Doubovetzky, M., Merino, R., Bessila, N., Angulo-Barturen, I., Baud, D., Bebrevska, L., Escudié, F., Niles, J.C., Blasco, B., Campbell, S., Courtemanche, G., Fraisse, L., Pellet, A., Fidock, D.A. and Leroy, D. (2021) The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to Plasmodium falciparum parasite resistance. Sci. Transl. Med. 13: eabg6013. PMC8530196.
Stokes, B.H., Dhingra, S.K., Rubiano, K., Mok, S., Straimer, J., Gnädig, N.F., Deni, I., Schindler, K.A., Bath, J.R., Ward, K.E., Striepen, J., Yeo, T., Ross, L. S., Legrand, E., Ariey, F., Cunningham, C.H., Souleymane, I.M., Gansané, A., Nzoumbou-Boko, R., Ndayikunda, C., Kabanywanyi, A.M., Uwimana, A., Smith, S.J., Kolley, O., Ndounga, M., Warsame, M., Leang, R., Nosten, F., Anderson, T.J., Rosenthal, P.J., Ménard, D. and Fidock, D.A. (2021) Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness. Elife 10: e66277. PMC8321553.
Okombo, J., Kanai, M., Deni, I. and Fidock, D.A. (2021) Genomic and genetic approaches to studying antimalarial drug resistance and Plasmodium biology. Trends Parasitol. 37: 476-492. PMC8162148.
Vanaerschot, M., Murithi, J.M., Pasaje, C.F.A., Ghidelli-Disse, S., Dwomoh, L., Bird, M., Spottiswoode, N., Mittal, N., Arendse, L.B., Owen, E.S., Wicht, K.J., Siciliano, G., Bosche, M., Yeo, T., Kumar, T.R.S., Mok, S., Carpenter, E.F., Giddins, M.J., Sanz, O., Ottilie, S., Alano, P., Chibale, K., Llinas, M., Uhlemann, A.C., Delves, M., Tobin, A.B., Doerig, C., Winzeler, E.A., Lee, M.C.S., Niles, J.C. and Fidock, D.A. (2020). Inhibition of resistance-refractory P. falciparum kinase PKG delivers prophylactic, blood stage, and transmission-blocking antiplasmodial activity. Cell Chem. Biol. 27: 806-16. PMC7369637.
Gnadig, N.F., Stokes, B.H., Edwards, R.L., Kalantarov, G.F., Heimsch, K.C., Kuderjavy, M., Crane, A., Lee, M.C.S., Straimer, J., Becker, K., Trakht, I.N., Odom John, A.R., Mok, S. and Fidock, D.A. (2020). Insights into the intracellular localization, protein associations and artemisinin resistance properties of Plasmodium falciparum K13. PLoS Pathog. 16: e1008482. PMC7192513.
Small-Saunders, J.L., Hagenah, L.M. and Fidock, D.A. (2020) Turning the tide: targeting PfCRT to combat drug-resistant P. falciparum? Nature Rev. Microbiol. 18: 261-262. PMC7269106.
Mok, S., Stokes, B.H., Gnädig, N.F., Ross L.S., Yeo, T., Amaratunga, C., Allman, E, Solyakov, L, Bottrill, AR, Tripathi, J., Fairhurst, R.M., Llinás, M., Bozdech, Z., Tobin, A.B. and Fidock, D.A. (2021) Artemisinin-resistant K13 mutations rewire Plasmodium falciparum’s intra-erythrocytic metabolic program to enhance survival. Nature Commun. 12: 530. PMC7822823.
Dorjsuren, D., Eastman, R.T., Wicht, K.J., Jansen, D., Talley, D.C., Sigmon, B.A., Zakharov, A.V., Roncal, N., Girvin, A.T., Antonova-Koch, Y., Will, P.M., Shah, P., Sun, H., Klumpp-Thomas, C., Mok, S., Yeo, T., Meister, S., Marugan, J.J., Ross, L.S., Xu, X., Maloney, D.J., Jadhav, A., Mott, B.T., Sciotti, R.J., Winzeler, E.A., Waters, N.C., Campbell, R.F., Huang, W., Simeonov, A. and Fidock, D.A. (2021) Chemoprotective antimalarials identified through quantitative high-throughput screening of Plasmodiumblood and liver stage parasites. Sci. Rep. 11: 2121. PMC7822874.
Uwimana, A., Legrand, E., Stokes, BH., Ndikumana, JM., Warsame, M., Umulisa, N., Ngamije, D., Munyaneza, T., Mazarati, JB., Munguti, K., Campagne, P., Criscuolo, A., Ariey, F., Murindahabi, M., Ringwald, P., Fidock, D.A., Mbituyumuremyi, A. and Ménard, D. (2020) Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nature Med. 26: 1602-1608. PMC7541349.
Wicht, K.J., Mok, S. and Fidock, D.A. (2020) Molecular mechanisms of drug resistance in Plasmodium falciparum malaria. Annual Rev. Microbiol. 74: 431-454. PMC8130186.
LaMonte, G.M., Rocamora, F., Marapana, D.S., Gnädig, N.F., Ottilie, S., Luth, M.R., Worgall, T.S., Goldgof, G.M., Mohunlal, R., Santha Kumar, T.R., Thompson, J.K., Vigil, E., Yang, J., Hutson, D., Johnson, T., Huang, J., Williams, R.M., Zou, B.Y., Cheung, A.L., Kumar, P., Egan, T.J., Lee, M.C.S., Siegel, D., Cowman, A.F., Fidock, D.A. and Winzeler E.A. (2020) Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway. Nature Commun. 11:1780. PMC7156427.
Kim, J., Tan, Y.Z., Wicht, K.J., Erramilli, S.K., Dhingra, S.K., Okombo, J., Vendome, J., Hagenah, L.M., Giacometti, S.I., Warren, A.L., Nosol, K., Roepe, P.D., Potter, C.S., Carragher, B., Kossiakoff, A.A., Quick, M., Fidock, D.A.* and Mancia, F.* (2019) Structure and drug resistance of the Plasmodium falciparum transporter PfCRT. Nature 576: 315-320. *Co-corresponding authors. PMC8130186.
Dhingra, S.K., Small-Saunders, J.L., Ménard, D. and Fidock, D.A. (2019) Plasmodium falciparumresistance to piperaquine driven by PfCRT. Lancet Infect. Dis. 19: 1168-1169. PMC6943240.
Ross, L.S. and Fidock, D.A. (2019) Elucidating mechanisms of drug-resistant Plasmodium falciparum. Cell Host Microbe 26: 35-47. PMC6639022.
McLean, K.J., Straimer, J., Hopp, C.S., Vega-Rodriguez, J., Small-Saunders, J.L., Kanatani, S., Tripathi, A., Mlambo, G., Dumoulin, P.C., Harris, C.T., Tong, X., Shears, M.J., Ankarklev, J., Kafsack, B.F.C., Fidock, D.A. and Sinnis, P. (2019) Generation of transmission-competent human malaria parasites with chromosomally-integrated fluorescent reporters. Sci. Rep. 9: 13131. PMC6739413.
Ménard, D. and Fidock, D.A. (2019) Accelerated evolution and spread of multidrug-resistant Plasmodium falciparum takes down the latest first-line antimalarial drug in southeast Asia. Lancet Infect. Dis. 19: 916-917. PMC6754981.
Stokes, B.H., Yoo, E., Murithi, J.M., Luth, M.R., Afanasyev, P., da Fonseca, P.C.A., Winzeler, E.A., Ng, C.L., Bogyo, M. and Fidock, D.A. (2019) Covalent Plasmodium falciparum-selective proteasome inhibitors exhibit a low propensity for generating resistance in vitro and synergize with multiple antimalarial agents. PLoS Pathog. 15: e1007722. PMC6553790.
Dhingra, S.K., Gabryszewski, S.J., Small-Saunders, J.L., Yeo, T., Henrich, P.P., Mok, S. and Fidock, D.A. (2019) Global spread of mutant PfCRT and its pleiotropic impact on Plasmodium falciparum multidrug resistance and fitness. MBio 10: mBio.02731-18. PMC6495381.
Bunnik, E.M., Venkat, A., Shao, J., McGovern, K.E., Batugedara, G., Worth, D., Prudhomme, J., Lapp, S.A., Andolina, C., Ross, L.S., Lawres, L., Brady, D., Sinnis, P., Nosten, F., Fidock, D.A., Wilson, E.H., Tewari, R., Galinski, M.R., Ben Mamoun, C., Ay, F. and Le Roch, K.G. (2019) Comparative 3D genome organization in apicomplexan parasites. Proc. Natl. Acad. Sci. U.S.A. 116: 3183-3192. PMC6386730.
Antonova-Koch, Y., Meister, S., Abraham, M., Luth, M.R., Ottilie, S., Lukens, A.K., Sakata-Kato, T., Vanaerschot, M., Owen, E., Jado, J.C., Maher, S.P., Calla, J., Plouffe, D., Zhong, Y., Chen, K., Chaumeau, V., Conway, A.J., McNamara, C.W., Ibanez, M., Gagaring, K., Serrano, F.N., Eribez, K., Taggard, C.M., Cheung, A.L., Lincoln, C., Ambachew, B., Rouillier, M., Siegel, D., Nosten, F., Kyle, D.E., Gamo, F.J., Zhou, Y., Llinas, M., Fidock, D.A., Wirth, D.F., Burrows, J., Campo, B. and Winzeler, E.A. (2018) Open-source discovery of chemical leads for next-generation chemoprotective antimalarials. Science 362: eaat9446. PMC6516198.
Ross, L.S., Dhingra, S.K., Mok, S., Yeo, T., Wicht, K.J., Kumpornsin, K., Takala-Harrison, S., Witkowski, B., Fairhurst, R.M., Ariey, F., Menard, D. and Fidock, D.A. (2018) Emerging Southeast Asian PfCRT mutations confer Plasmodium falciparum resistance to the first-line antimalarial piperaquine. Nature Commun. 9: 3314. PMC6095916.
Cowell, A.N., Istvan, E.S., Lukens, A.K., Gomez-Lorenzo, M.G., Vanaerschot, M., Sakata-Kato, T., Flannery, E.L., Magistrado, P., Owen, E., Abraham, M., LaMonte, G., Painter, H.J., Williams, R.M., Franco, V., Linares, M., Arriaga, I., Bopp, S., Corey, V.C., Gnadig, N.F., Coburn-Flynn, O., Reimer, C., Gupta, P., Murithi, J.M., Moura, P.A., Fuchs, O., Sasaki, E., Kim, S.W., Teng, C.H., Wang, L.T., Akidil, A., Adjalley, S., Willis, P.A., Siegel, D., Tanaseichuk, O., Zhong, Y., Zhou, Y., Llinas, M., Ottilie, S., Gamo, F.J., Lee, M.C.S., Goldberg, D.E., Fidock, D.A., Wirth, D.F. and Winzeler, E.A. (2018) Mapping the malaria parasite druggable genome by using in vitroevolution and chemogenomics. Science 359: 191-199. PMC5925756.
Vanaerschot, M., Lucantoni, L., Li, T., Combrinck, J.M., Ruecker, A., Kumar, T.R.S., Rubiano, K., Ferreira, P.E., Siciliano, G., Gulati, S., Henrich, P.H., Ng, C.L., Murithi, J.M., Corey, V.C., Duffy, S., Lieberman, O.J., Veiga, M.I., Sinden, R.E., Alano, P., Delves, M.J., Sim, K.L., Winzeler, E.A., Egan, T.J., Hoffman, S.L., Avery, V.M. and Fidock, D.A. (2017). Hexahydroquinolines are antimalarial candidates with potent blood stage and transmission-blocking activity. Nature Microbiol. 2: 1403-1414. PMC5708124.
Blasco, B., Leroy, D. and Fidock, D.A. (2017). Antimalarial drug resistance: linking Plasmodium falciparum parasite biology with the clinic. Nature Med. 23: 917-928. PMC5747363.
Dhingra, S.K., Redhi, D., Combrinck, J.M., Yeo, T., Okombo, J., Henrich, P.P., Cowell, A.N., Gupta, P., Stegman, M.L., Hoke, J.M., Cooper, R.A., Winzeler, E., Mok, S., Egan, T.J. and Fidock, D.A. (2017). A variant pfcrt isoform can contribute to Plasmodium falciparum resistance to the first-line partner drug piperaquine. mBio 8: e00303-00317. PMC5424201.
Gabryszewski, S.J., Dhingra, S.K., Combrinck, J.M., Lewis, I.A., Callaghan, P.S., Hassett, M.R, Siriwardana, A., Henrich, P.P., Lee, A.H., Gnädig, N.F., Musset, L., Llinás, M., Egan, T.J., Roepe, P.D. and Fidock, D.A. (2016). Evolution of fitness cost-neutral mutant PfCRT conferring P. falciparum 4-aminoquinoline drug resistance is accompanied by altered parasite metabolism and digestive vacuole physiology. PLoS Pathogens 12: e1005976. PMC5104409.
Veiga MI, Dhingra SK, Henrich PP, Straimer J, Gnadig N, Uhlemann AC, Martin RE, Lehane AM and Fidock DA (2016). Globally prevalent PfMDR1 mutations modulate Plasmodium falciparumsusceptibility to artemisinin-based combination therapies. Nature Commun. 7: 11553. PMC4873939.
Ng, C.L., Siciliano, G., Lee, M.C., de Almeida, M.J., Corey, V.C., Bopp, S.E., Bertuccini, L., Wittlin, S., Kasdin, R.G., Le Bihan, A., Clozel, M., Winzeler, E.A., Alano, P. and Fidock, D.A. (2016). CRISPR-Cas9-modified pfmdr1 protects Plasmodium falciparum asexual blood stages and gametocytes against a class of piperazine-containing compounds but potentiates artemisinin-based combination. Mol Microbiol. 101: 381-393. PMC4958522.
Gabryszewski, S.J., Modchang, C., Musset, L., Chookajorn, T. and Fidock, D.A. (2016). Combinatorial genetic modeling of pfcrt-mediated drug resistance evolution in Plasmodium falciparum. Mol. Biol. Evol. 33: 1554-1570. PMC4868112.
Gulati, S., Ekland, E.H., Ruggles, K.V., Chan, R.B., Jayabalasingham, B., Zhou, B., Mantel, P.Y., Lee, M.C., Spottiswoode, N., Coburn-Flynn, O., Hjelmqvist, D., Worgall, T.S., Marti, M., Di Paolo, G. and Fidock, D.A. (2015) Profiling the essential nature of lipid metabolism in asexual blood and gametocyte stages of Plasmodium falciparum. Cell Host Microbe 18: 371-381. PMC4567697.
Baragana, B., Hallyburton, I., Lee, M.C., Norcross, N.R., Grimaldi, R., Otto, T.D., Proto, W.R., Blagborough, A.M., Meister, S., Wirjanata, G., Ruecker, A., Upton, L.M., Abraham, T.S., Almeida, M.J., Pradhan, A., Porzelle, A., Martinez, M.S., Bolscher, J.M., Woodland, A., Norval, S., Zuccotto, F., Thomas, J., Simeons, F., Stojanovski, L., Osuna-Cabello, M., Brock, P.M., Churcher, T.S., Sala, K.A., Zakutansky, S.E., Jimenez-Diaz, M.B., Sanz, L.M., Riley, J., Basak, R., Campbell, M., Avery, V.M., Sauerwein, R.W., Dechering, K.J., Noviyanti, R., Campo, B., Frearson, J.A., Angulo-Barturen, I., Ferrer-Bazaga, S., Gamo, F.J., Wyatt, P.G., Leroy, D., Siegl, P., Delves, M.J., Kyle, D.E., Wittlin, S., Marfurt, J., Price, R.N., Sinden, R.E., Winzeler, E.A., Charman, S.A., Bebrevska, L., Gray, D.W., Campbell, S., Fairlamb, A.H., Willis, P.A., Rayner, J.C., Fidock, D.A., Read, K.D. and Gilbert, I.H. (2015) A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature 522: 315-320. PMC4700930.
Straimer, J., Gnadig, N.F., Witkowski, B., Amaratunga, C., Duru, V., Ramadani, A.P., Dacheux, M., Khim, N., Zhang, L., Lam, S., Gregory, P.D., Urnov, F.D., Mercereau-Puijalon, O., Benoit-Vical, F., Fairhurst, R.M., Menard, D. and Fidock, D.A. (2015) Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science347: 428-431. PMC4349400.
Lee, M.C. and Fidock, D.A. (2014) CRISPR-mediated genome editing of Plasmodium falciparum malaria parasites. Genome Med. 6: 63. PMC4254425.
Lee, A.H., Symington, L.S. and Fidock, D.A. (2014) DNA repair mechanisms and their biological roles in the malaria parasite Plasmodium falciparum. Microbiol. Mol. Biol. Rev. 78: 469-486. PMC4187680.
Lisewski, A.M., Quiros, J.P., Ng, C.L., Adikesavan, A.K., Miura, K., Putluri, N., Eastman, R.T., Scanfeld, D., Regenbogen, S.J., Altenhofen, L., Llinas, M., Sreekumar, A., Long, C., Fidock, D.A. and Lichtarge, O. (2014) Supergenomic network compression and the discovery of EXP1 as a glutathione transferase inhibited by artesunate. Cell 158: 916-928. PMC4167585.
Johnston, G.L., Gething, P.W., Hay, S.I., Smith, D.L. and Fidock, D.A. (2014) Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination. PLoS Comput. Biol. 10: e1003434. PMC3900379.
McNamara,* C.W., Lee,* M.C., Lim, C.S., Lim, S.H., Roland, J., Simon, O., Yeung, B.K.S., Chatterjee, A.K., McCormack, S.L., Manary, M.J., Zeeman, A.-M., Dechering, K.J., Kumar, T.R., Henrich, P.P., Gagaring, K., Ibanez, M., Kato, N., Kuhen, K.L., Fischli, C., Nagle, C., Rottmann, M., Plouffe, D.M., Bursulaya, B., Meister, S., Rameh, L., Trappe, J., Haasen, D., Timmerman, M., Sauerwein, R.W., Suwanarusk, R., Russell, B., Renia, L., Nosten, F., Tully, D.C., Kocken, C.H.M., Glynne, R.J., Bodenreider, C., Fidock, D.A., Diagana, T.T. and Winzeler, E.A. (2013). Targeting Plasmodiumphosphatidylinositol-4 kinase to eliminate malaria. Nature 504: 248-253. *Co-first. PMC3940870.
Johnston. G.L., Gething, P.W., Hay, S.I., Smith, D.L. and Fidock, D.A. (2013). Modeling within-host effects of drugs on transmission and prospects for malaria elimination. PLoS Comput. Biol. 9: e1003025. PMC3900379.
Fidock, D.A. (2013) Eliminating malaria. Science 340: 1531-1533. doi: 10.1126/science.1240539.
Johnston, G.L., Smith, D.L. and Fidock, D.A. (2013) Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission. PLoS Comp. Biol. 9: e1003025. PMC3630126.
Falkard, B., Kumar, T.R., Hecht, L.S., Matthews, K.A., Henrich, P.P., Gulati, S., Lewis, R.E., Manary, M.J., Winzeler, E.A., Sinnis, P., Prigge, S.T., Heussler, V., Deschermeier, C. and Fidock, D.A. (2013) A key role for lipoic acid synthesis during Plasmodium liver stage development. Cell Microbiol. 15: 1585-1604. PMC3740003.
Straimer, J., Lee, M.C., Lee, A.H., Zeitler, B., Williams, A.E., Pearl, J.R., Zhang, L., Rebar, E.J., Gregory, P.D., Llinas, M., Urnov, F.D. and Fidock, D.A. (2012) Site-specific genome editing in Plasmodium falciparum using engineered zinc-finger nucleases. Nature Methods 9: 993-998. PMC3697006.
Crabb, B.S., Beeson, J.G., Amino, R., Menard, R., Waters, A., Winzeler, E.A., Wahlgren, M., Fidock, D.A. and Nwaka, S. (2012) Perspectives: The missing pieces. Nature. 484: S22-23.
Uhlemann, A.C. and Fidock, D.A. (2012) Loss of malarial susceptibility to artemisinin in Thailand. Lancet 379: 1928-1930. doi: 10.1016/S0140-6736(12)60488-7.
Meister, S., Plouffe, D.M., Kuhen, K.L., Bonamy, G.M., Wu, T., Barnes, S.W., Bopp, S.E., Borboa, R., Bright, A.T., Che, J., Cohen, S., Dharia, N.V., Gagaring, K., Gettayacamin, M., Gordon, P., Groessl, T., Kato, N., Lee, M.C., McNamara, C.W., Fidock, D.A., Nagle, A., Nam, T.G., Richmond, W., Roland, J., Rottmann, M., Zhou, B., Froissard, P., Glynne, R.J., Mazier, D., Sattabongkot, J., Schultz, P.G., Tuntland, T., Walker, J.R., Zhou, Y., Chatterjee, A., Diagana, T.T. and Winzeler, E.A. (2011) Imaging of Plasmodiumliver stages to drive next-generation antimalarial drug discovery. Science 334: 1372-1377. PMC3473092.
Adjalley, S.H., Johnston, G.L., Li, T., Eastman, R.T., Ekland, E.H., Eappen, A.G., Richman, A., Sim, B.K., Lee, M.C., Hoffman, S.L. and Fidock, D.A. (2011) Quantitative assessment of Plasmodium falciparumsexual development reveals potent transmission-blocking activity by methylene blue. Proc. Natl. Acad. Sci. U.S.A. 108: E1214-1223. PMC3223476.
Rottmann, M., McNamara, C., Yeung, B.K.S., Lee, M.C.S., Zou, B., Russell, B., Seitz, P., Dharia, N.V., Plouffe, D.M., Tan, J., Cohen, S.B., Spencer, K.R., Gonzalez-Paez, G.E., Lakshminarayana, S.B., Goh, A., Suwanarusk, R., Jegla, T., Schmitt, E.K., Beck, H.-P., Brun, R., Nosten, F., Renia, L., Dartois, V., Keller, T.H., Fidock, D.A., Winzeler, E.A. and Diagana, T.T. (2010). Spiroindolones, a potent chemotype for the treatment of malaria. Science 329: 1175-1180. PMC3050001.
Valderramos, S.G., Valderramos J.C., Musset L., Purcell L.A., Mercereau-Puijalon O., Legrand E. and Fidock D.A. (2010). Identification of a mutant PfCRT-mediated chloroquine tolerance phenotype in Plasmodium falciparum. PLoS Pathogens 6: e1000887. PMC2869323. [Download PDF]
Fidock, D.A. (2010). Drug discovery: Priming the antimalarial pipeline. Nature 465: 297-8. PMID: 20485420.
Eastman, R.E. and Fidock, D.A. (2009). Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria. Nature Rev. Microbiol. 7: 864-874. PMC2901398.
Yu, M., Kumar, T.R.S., Nkrumah, L.J., Coppi, A., Retzlaff, S., Li, C.D., Kelly, B.J., Moura, P.A., Lakshmanan, V., Freundlich, J.S., Valderramos, J.C., Vilcheze, C., Siedner, M., Tsai, J.H.C., Falkard, B., Sidhu, A.B.S., Purcell, L.A., Gratraud, P., Kremer, L., Waters, A.P., Schiehser, G., Jacobus, D.P., Janse, C.J., Ager, A., Jacobs, Jr. W.R., Sacchettini, J.C., Heussler, V., Sinnis, P. and Fidock, D.A. (2008). The fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites. Cell Host & Microbe.11: 567-578. Cover article featured in the same issue of Cell Host & Microbe and reviewed in Nature Reviews in Microbiology 7: 94. PMC2646117. [Download PDF]
Greenwood, B.M., Fidock, D.A., Kyle, D.E., Kappe, S.H., Collins, F.H. and Duffy, P.E. (2008). Malaria: progress, perils, and prospects for eradication. J. Clin. Invest. 118: 1266-1276. PMC2276780.[Download PDF]
Nkrumah L.N., Muhle R.A., Moura P.A., Ghosh P., Hatfull G., Jacobs Jr. W.R. and Fidock D.A. (2006). Efficient site-specific integration in Plasmodium falciparum chromosomes mediated by mycobacteriophage Bxb1 integrase. Nature Methods 3: 615-621. PMC2943413.
Lakshmanan, V., Bray, P.G., Verdier-Pinard, D., Johnson, D.J., Horrocks, P., Muhle, R.A., Alakpa, G.E., Hughes, R.H., Ward, S.A., Krogstad, D.J., Sidhu, A.B.S. and Fidock, D.A. (2005). A critical role for PfCRT K76T in Plasmodium falciparum verapamil-reversible chloroquine resistance. EMBO J. 24: 2294-2305. PMC1173140. [Download PDF]
Johnson, D.J., Fidock, D.A.*, Mungthin, M., Lakshmanan, V., Sidhu, A.B.S., Bray, P.G., and Ward, S.A.* (2004) Evidence for a central role for PfCRT in conferring Plasmodium falciparum resistance to diverse antimalarial agents. Mol. Cell 15: 867-877. (*Co-corresponding authors). PMC2943419. [Download PDF]
Fidock, D.A., Rosenthal, P.J., Croft, S.L., Brun, R. and Nwaka, S. (2004). Antimalarial drug discovery: efficacy models for compound screening. Nature Rev. Drug Disc. 3: 509-520. PMID: 15173840. [Download PDF]
Sidhu, A.B.S., Verdier-Pinard, D. and Fidock, D.A. (2002). Chloroquine resistance to Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science 298: 210-213. PMC2954758. [Download PDF]
Djimde, A., Doumbo, O.K., Cortese, J.F., Kayentao, K., Doumbo, S., Diourte, Y., Coulibaly, D., Dicko, A., Su, X-z., Nomura, T., Fidock, D.A., Wellems, T.E. and Plowe, C.V. (2001). A molecular marker for chloroquine resistant falciparum malaria. New Engl. J. Med. 344: 257-63. PMID: 11172152.
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