Our research program focuses on seven subject areas: (1) the nature of protection against malaria that is conferred to individuals carrying red blood cell (RBC) polymorphisms including hemoglobin C, hemoglobin S, hemoglobin E, alpha-thalassemia and G6PD deficiency;(2) the nature of infant protection against malaria in the first few months of life, involving cooperative interactions between fetal hemoglobin and maternal-derived immune antibodies;(3) the nature of naturally-acquired immunity to malaria and how it is influenced by RBC polymorphisms;(4) the molecular mechanisms by which RBC polymorphisms reduce the expression of PfEMP1, the main virulence factor of Plasmodium falciparum, on the surface of parasitized RBCs;(5) the nature of microvessel inflammation and other pathogenic processes caused by the adherence of parasitized RBCs to human microvascular endothelial cells and by the release of parasite-induced uric acid aggregates;(6) the contributions of parasite genetic and host immune factors to the clearance of P. falciparum-infected RBCs in patients treated with the antimalarial drug artesunate;and (7) the nature of the selective invasion of reticulocytes by Plasmodium vivax. In each of these areas we seek research advances that can improve the knowledge of disease processes and antimalarial drug resistance mechanisms in patients with malaria and thereby support the development of new antimalarial therapeutics and vaccines that aim to prevent illness and death. The research activities in our program are multidisciplinary and include four field studies in malarious regions of Africa and Asia as well as programs of basic laboratory investigation at NIH-sponsored laboratories in Mali and Cambodia.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2012
Total Cost
$768,635
Indirect Cost
City
State
Country
Zip Code
Hamilton, William L; Claessens, Antoine; Otto, Thomas D et al. (2017) Extreme mutation bias and high AT content in Plasmodium falciparum. Nucleic Acids Res 45:1889-1901
Tétard, Marilou; Milet, Jacqueline; Dechavanne, Sébastien et al. (2017) Heterozygous HbAC but not HbAS is associated with higher newborn birthweight among women with pregnancy-associated malaria. Sci Rep 7:1414
Adomako-Ankomah, Yaw; Chenoweth, Matthew S; Durfee, Katelyn et al. (2017) High Plasmodium falciparum longitudinal prevalence is associated with high multiclonality and reduced clinical malaria risk in a seasonal transmission area of Mali. PLoS One 12:e0170948
Longley, Rhea J; França, Camila T; White, Michael T et al. (2017) Asymptomatic Plasmodium vivax infections induce robust IgG responses to multiple blood-stage proteins in a low-transmission region of western Thailand. Malar J 16:178
Mukherjee, Angana; Bopp, Selina; Magistrado, Pamela et al. (2017) Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia. Malar J 16:195
Morita, Masayuki; Takashima, Eizo; Ito, Daisuke et al. (2017) Immunoscreening of Plasmodium falciparum proteins expressed in a wheat germ cell-free system reveals a novel malaria vaccine candidate. Sci Rep 7:46086
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Amato, Roberto; Lim, Pharath; Miotto, Olivo et al. (2017) Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study. Lancet Infect Dis 17:164-173
Soucy, Katie; Fairhurst, Rick M; Lynn, Geoffrey M et al. (2016) Breaking the Mold: Partnering with the National Institutes of Health Intramural Research Program to Accelerate PhD Training. Trends Immunol 37:813-815
Diakite, Mahamadou; Miura, Kazutoyo; Diouf, Ababacar et al. (2016) Hematological Indices in Malian Children Change Significantly During a Malaria Season and with Increasing Age: Implications for Malaria Epidemiological Studies. Am J Trop Med Hyg 95:368-72

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