Our research program focuses on four subject areas: (1) the nature of protection against malaria that is conferred to individuals carrying hemoglobin mutations and red blood cell polymorphisms including but not limited to hemoglobin C, hemoglobin S, hemoglobin E, alpha- and beta-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 molecular mechanisms by which malaria-protective polymorphisms reduce the expression of PfEMP-1, the main virulence factor of Plasmodium falciparum, on the surface of parasitized red blood cells;(4) the nature of microvessel inflammation and other pathogenic processes caused by the adherence of parasitized red blood cells to human microvascular endothelial cells and blood monocytes. In each of these areas we seek research advances that can improve the knowledge of fatal disease processes in individuals with malaria and thereby support the development of new antimalarial therapeutics and vaccines that aim to prevent death. The research activities in our program are multidisciplinary and include three field studies in malarious regions of Africa and Asia as well as programs of basic laboratory investigation.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2010
Total Cost
$832,448
Indirect Cost
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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
Ataide, Ricardo; Ashley, Elizabeth A; Powell, Rosanna et al. (2017) Host immunity to Plasmodium falciparum and the assessment of emerging artemisinin resistance in a multinational cohort. Proc Natl Acad Sci U S A 114:3515-3520
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
Leang, Rithea; Khu, Naw Htee; Mukaka, Mavuto et al. (2016) An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia. BMC Med 14:171
Bustos-Arriaga, José; Mita-Mendoza, Neida K; Lopez-Gonzalez, Moises et al. (2016) Soluble mediators produced by the crosstalk between microvascular endothelial cells and dengue-infected primary dermal fibroblasts inhibit dengue virus replication and increase leukocyte transmigration. Immunol Res 64:392-403

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