Professor David A. Fidock Phone: 212-305-0816  Lab Phone: 212-305-6958 Fax: 212-305-4038  Email: df2260@columbia.edu Website: fidock.org

Professor David A. Fidock
Phone: 212-305-0816
Lab Phone: 212-305-6958
Fax: 212-305-4038
Email: df2260@columbia.edu
Website: fidock.org

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.

 

Selected Publications


  1. 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.

  2. Mok, S. and Fidock, D.A. (2023). Determinants of piperaquine-resistant malaria in South America. Lancet Infect. Dis. 16: S1473-3099(23)00564-9. Epub ahead of print. PMID: 37858324.

  3. 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.

  4. 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.

  5. 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.

  6. 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. PMID: 36260689.

  7. 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. doi: 10.1093/infdis/jiac365. PMID: 36082431

  8. 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. doi: 10.1371/journal.ppat.1010926. PMID: 36306287

  9. 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. doi: 10.1126/scitranslmed.abo7219. PMID: 36260689

  10. 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. doi: 10.1056/NEJMc2117480. PMID: 35388682

  11. Sinnis, P. and Fidock, D.A. (2022) The RTS,S vaccine-a chance to regain the upper hand against malaria? Cell 185: 750-754. doi: 10.1016/j.cell.2022.01.028. PMID: 35245476

  12. 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. doi: 10.1371/journal.ppat.1010278. PMID: 35130315

  13. 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, randomised, placebo-controlled, double-blind, single ascending dose study and volunteer infection study. Lancet Infect. Dis. 21: 1713-1724. doi: 10.1016/S1473-3099(21)00252-8. PMID: 34715032

  14. Thathy, V. and Fidock, D.A. (2021) Malaria parasite beats the heat. Nature Microbiol. 6: 1105-1107. doi: 10.1038/s41564-021-00953-5. PMID: 34400834

  15. 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.

  16. Fidock, D.A. and Rosenthal, P.J. (2021) Artemisinin resistance in Africa: How urgent is the threat? Med. 2: 1287-8. PMC8729812.

  17. 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. doi: 10.1126/scitranslmed.abg6013. PMID: 34290058

  18. 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. doi: 10.7554/eLife.66277. PMID: 34279219

  19. 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. doi: 10.1016/j.pt.2021.02.007. PMID: 33715941

  20. 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. PMID: 32359426.

  21. 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.

  22. 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. doi: 10.1038/s41579-020-0353-8. PMID: 32300249

  23. 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.

  24. 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 Plasmodium blood and liver stage parasites. Sci. Rep. 11: 2121.

  25. 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.

  26. 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.

  27. 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.

  28. 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.

  29. Dhingra, S.K., Small-Saunders, J.L., Ménard, D. and Fidock, D.A. (2019) Plasmodium falciparum resistance to piperaquine driven by PfCRT. Lancet Infect. Dis. 19: 1168-1169.

  30. Ross, L.S. and Fidock, D.A. (2019) Elucidating mechanisms of drug-resistant Plasmodium falciparum. Cell Host Microbe 26: 35-47.

  31. 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.

  32. 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.

  33. 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.

  34. 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.

  35. 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.

  36. 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.

  37. Sa, J.M., Kaslow, S.R., Krause, M.A., Melendez-Muniz, V.A., Salzman, R.E., Kite, W.A., Zhang, M., Moraes Barros, R.R., Mu, J., Han, P.K., Mershon, J.P., Figan, C.E., Caleon, R.L., Rahman, R.S., Gibson, T.J., Amaratunga, C., Nishiguchi, E.P., Breglio, K.F., Engels, T.M., Velmurugan, S., Ricklefs, S., Straimer, J., Gnadig, N.F., Deng, B., Liu, A., Diouf, A., Miura, K., Tullo, G.S., Eastman, R.T., Chakravarty, S., James, E.R., Udenze, K., Li, S., Sturdevant, D.E., Gwadz, R.W., Porcella, S.F., Long, C.A., Fidock, D.A., Thomas, M.L., Fay, M.P., Sim, B.K.L., Hoffman, S.L., Adams, J.H., Fairhurst, R.M., Su, X.Z. and Wellems, T.E. (2018) Artemisinin resistance phenotypes and K13 inheritance in a Plasmodium falciparum cross and Aotus model. Proc. Natl. Acad. Sci. U.S.A. 115: 12513-12518.

  38. Lee, A.H., Dhingra, S.K., Lewis, I.A., Singh, M.K., Siriwardana, A., Dalal, S., Rubiano, K., Klein, M.S., Baska, K.S., Krishna, S., Klemba, M., Roepe, P.D., Llinas, M., Garcia, C.R.S. and Fidock, D.A. (2018) Evidence for regulation of hemoglobin metabolism and intracellular ionic flux by the Plasmodium falciparum Chloroquine Resistance Transporter. Sci. Rep. 8: 13578.

  39. 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.

  40. Llanos-Cuentas, A., Casapia, M., Chuquiyauri, R., Hinojosa, J.C., Kerr, N., Rosario, M., Toovey, S., Arch, R.H., Phillips, M.A., Rozenberg, F.D., Bath, J., Ng, C.L., Cowell, A.N., Winzeler, E.A., Fidock, D.A., Baker, M., Mohrle, J.J., Hooft van Huijsduijnen, R., Gobeau, N., Araeipour, N., Andenmatten, N., Ruckle, T. and Duparc, S. (2018) Antimalarial activity of single-dose DSM265, a novel plasmodium dihydroorotate dehydrogenase inhibitor, in patients with uncomplicated Plasmodium falciparum or Plasmodium vivax malaria infection: a proof-of-concept, open-label, phase 2a study. Lancet Infect. Dis. 18: 874-883.

  41. Bunnik, E.M., Cook, K.B., Varoquaux, N., Batugedara, G., Prudhomme, J., Cort, A., Shi, L., Andolina, C., Ross, L.S., Brady, D., Fidock, D.A., Nosten, F., Tewari, R., Sinnis, P., Ay, F., Vert, J.P., Noble, W.S. and Le Roch, K.G. (2018) Changes in genome organization of parasite-specific gene families during the Plasmodium transmission stages. Nature Commun. 9: 1910.

  42. Fidock, D.A. (2018) A Breathprint for Malaria: New opportunities for noninterventional diagnostics and mosquito traps? J. Infect. Dis. 217: 1512-1514.

  43. 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.

  44. 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.

  45. 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.

  46. Ng, C.L., Fidock, D.A. and Bogyo, M. (2017). Protein degradation systems as anti-malarial therapeutic targets. Trends Parasitol. 33: 731-743.

  47. 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. 

  48. Straimer, J., Gnädig, N.F., Stokes, B.H., Ehrenberger, M., Crane, A.C. and Fidock, D.A. (2017). Plasmodium falciparum K13 mutations differentially impact ozonide susceptibility and parasite fitness in vitro. mBio 8: e00172-17.

  49. Sonoiki, E., Ng, C.N., Lee, M.C.S., Guo, D., Zhang, Y.-K., Zhou, Y., Alley, M.R.K., Ahyong, V., Sanz-Alonso, L.M., Monasterio, M.J.L., Dong, C., Schupp, P.G., Gut, J., Legac, J., Cooper, R.A., Gamo, J.F., DeRisi, J., Freund, Y.R., Fidock, D.A. and Rosenthal, P.J. (2017). A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue. Nature Commun. 8: 14574.

  50. 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. 

  51. 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. 

  52. 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.

  53. 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.

  54. Adjalley, S.H., Scanfeld, D., Kozlowski, E., Llinas, M. and Fidock, D.A. (2015) Genome-wide transcriptome profiling reveals functional networks involving the Plasmodium falciparum drug resistance transporters PfCRT and PfMDR1. BMC Genomics 16: 1090.

  55. Pulcini, S., Staines, H.M., Lee, A.H., Shafik, S.H., Bouyer, G., Moore, C.M., Daley, D.A., Hoke, M.J., Altenhofen, L.M., Painter, H.J., Mu, J., Ferguson, D.J., Llinas, M., Martin, R.E., Fidock, D.A., Cooper, R.A. and Krishna, S. (2015) Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, enlarge the parasite's food vacuole and alter drug sensitivities. Sci. Rep. 5: 14552.

  56. 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.

  57. 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.

  58. Petersen, I., Gabryszewski, S.J., Johnston, G.L., Dhingra, S.K., Ecker, A., Lewis, R.E., de Almeida, M.J., Straimer, J., Henrich, P.P., Palatulan, E., Johnson, D.J., Coburn-Flynn, O., Sanchez, C., Lehane, A.M., Lanzer, M. and Fidock, D.A. (2015) Balancing drug resistance and growth rates via compensatory mutations in the Plasmodium falciparum chloroquine resistance transporter. Mol. Microbiol. 97: 381-395.

  59. 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.

  60. Lee, M.C. and Fidock, D.A. (2014) CRISPR-mediated genome editing of Plasmodium falciparum malaria parasites. Genome Med. 6: 63.

  61. Moraes Barros, R.R., Straimer, J., Sa, J.M., Salzman, R.E., Melendez-Muniz, V.A., Mu, J., Fidock, D.A.* and Wellems, T.E.* (2015) Editing the Plasmodium vivax genome, using zinc-finger nucleases. J. Infect. Dis. 211: 125-129. *Co-corresponding

  62. Lee, M.C. and Fidock, D.A. (2014) CRISPR-mediated genome editing of Plasmodium falciparum malaria parasites. Genome Med. 6: 63.

  63. 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.

  64. 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.

  65. 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.

  66. 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 Plasmodium phosphatidylinositol-4 kinase to eliminate malaria. Nature 504: 248-253. *Co-first

  67. van Schaijk, B.C.L.*, Kumar, T.R.S.*, Vosa, M.W., Richman, A., van Gemerta, G.-J., Li, T., Eappen, A.G., Williamson, K.C., Morahane, B.J., Fishbaugher, M., Kennedy, M., Camargo, N., Khan, S.M., Janse, C.J., Sim, K.L.H., Hoffman, S.L., Kappe, S.H., Sauerwein, R.W., Fidock, D.A.** and Vaughan, A.M.** (2013). Type II fatty acid biosynthesis is essential for Plasmodium falciparum sporozoite development in the midgut of Anopheles mosquitoes. Euk. Cell 13:550-559. *Co-first, **Co-corresponding

  68. 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.

  69. Bobenchik, A.M., Witola, W.H., Augagneur, Y., Lochlainn, L.N., Garg, A., Pachikara, N., Choi, J.-Y., Zhao, Y., Usmani-Brown, S., Lee, A., Adjalley, S.H., Samanta. S., Fidock, D.A., Voelker, D.R., Fikrig, E. and Ben Mamoun, C. (2013). Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission. Proc. Natl. Acad. Sci. USA 110:18262-18267. PMCID: 3831454.

  70. Fidock, D.A. (2013) Eliminating malaria. Science 340: 1531-1533.

  71. 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.

  72. 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.

  73. Ecker, A., Lewis, R.E., Ekland, E.H., Jayabalasingham, B. and Fidock, D.A. (2012) Tricks in Plasmodium's molecular repertoire - Escaping 3'-UTR excision-based conditional silencing of the chloroquine resistance transporter locus. Int. J. Parasitol. 42: 969-974.

  74. Ecker, A., Lehane, A.M., Clain, J. and Fidock, D.A. (2012) PfCRT and its role in antimalarial drug resistance. Trends Parasitol. 28: 504-514.

  75. 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.

  76. 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.

  77. Uhlemann, A.C. and Fidock, D.A. (2012) Loss of malarial susceptibility to artemisinin in Thailand. Lancet 379: 1928-1930.

  78. 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 Plasmodium liver stages to drive next-generation antimalarial drug discovery. Science 334: 1372-1377.

  79. 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 falciparum sexual development reveals potent transmission-blocking activity by methylene blue. Proc. Natl. Acad. Sci. U.S.A. 108: E1214-1223.

  80. Ecker, A., Lakshmanan, V., Sinnis, P., Coppens, I. and Fidock, D.A. (2010). Evidence that mutant PfCRT facilitates the transmission to mosquitoes of chloroquine-treated Plasmodium gametocytes. J. Infect. Dis. 203: 228-236.

  81. 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 new and potent chemotype for the treatment of malaria. Science 329: 1175-1180.

  82. 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. [Download PDF]

  83. Fidock, D.A. (2010). Drug discovery: Priming the antimalarial pipeline. Nature 465: 297-8.

  84. Melcher M., Muhle R.A., Henrich P., Kraemer S.M., Avril M., Vigan-Womas I., Mercereau-Puijalon O., Smith J.D. and Fidock D.A. (2010) Identification of a role for the PfEMP1 semi-conserved head structure in protein trafficking to the surface of Plasmodium falciparum infected red blood cells. Cell Microbiol. (in press). [Download PDF]

  85. 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.

  86. Dharia, N.V., Sidhu, A.B.S., Cassera, M.C., Westenberger, S., Bopp, S., Eastman, R.T., Plouffe, D., Batalov, S., Park, D.J., Volkman, S.K., Wirth, D.W., Zhou, Y., Fidock, D.A. and Winzeler, E.A. (2009). Use of high-density tiling microarrays to globally identify mutations and elucidate mechanisms of drug resistance in Plasmodium falciparum. Genome Biol. 10: R21. [Download PDF]

  87. 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. [Download PDF]

  88. Lee, M.C.S., Moura, P.A., Miller, E.A. and Fidock, D.A. (2008). Plasmodium falciparum Sec24 marks transitional ER that exports a model cargo via a diacidic motif. Mol. Microbiol. 68: 1535-1546. [Download PDF]

  89. 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. [Download PDF]

  90. Lee, M.C.S. and Fidock, D.A. (2008). Arresting malaria parasite egress from infected red blood cells. Nature Chem. Biol. 4: 161-162. [Download PDF]

  91. Sidhu, A.B., Sun, Q., Nkrumah, L.J., Dunne, M.W., Sacchettini, J.C. and Fidock, D.A. (2007). In vitro efficacy, resistance selection, and structural modeling studies implicate the malarial parasite apicoplast as the target of azithromycin. J. Biol. Chem. 282: 2494-2504.

  92. 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.

  93. 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. [Download PDF]

  94. 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) [Download PDF]

  95. 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. [Download PDF]

  96. Sidhu, A.B.S., Verdier-Pinard, D. and Fidock, D.A. (2002). pfcrt mutations confer chloroquine resistance to Plasmodium falciparum malaria parasites. Science 298: 210-213. [Download PDF]

  97. 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.

  98. Fidock, D.A., Nomura, T., Talley, A.K., Cooper, R.A., Dzekunov, S.M., Ferdig, M.T., Ursos, L.M., Sidhu, A.B.S., Deitsch, K., Su, X-z., Wootton, J.C., Roepe, P.D. and Wellems, T.E. (2000). Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol. Cell 6: 681-71. [Download PDF]

  99. Wellems, T.E., Wootton, J.C., Fujioka, H., Su, X., Cooper, R., Baruch, D. and Fidock, D.A. (1998). P. falciparum CG2, linked to chloroquine resistance, does not resemble Na+/H+ exchangers. Cell 94: 285-286. PMID: 9708730.

  100. Fidock, D.A. and Wellems, T.E. (1997). Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc. Natl. Acad. Sci. U.S.A. 94: 10931- 10936. PMC23535.