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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI001000-02
Application #
7732650
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2008
Total Cost
$144,940
Indirect Cost
City
State
Country
United States
Zip Code
Wellems, Thomas E; Hayton, Karen; Fairhurst, Rick M (2009) The impact of malaria parasitism: from corpuscles to communities. J Clin Invest 119:2496-505
Tokumasu, Fuyuki; Nardone, Glenn A; Ostera, Graciela R et al. (2009) Altered membrane structure and surface potential in homozygous hemoglobin C erythrocytes. PLoS One 4:e5828
Nagao, Eriko; Arie, Takayuki; Dorward, David W et al. (2008) The avian malaria parasite Plasmodium gallinaceum causes marked structural changes on the surface of its host erythrocyte. J Struct Biol 162:460-7
Cholera, Rushina; Brittain, Nathaniel J; Gillrie, Mark R et al. (2008) Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin. Proc Natl Acad Sci U S A 105:991-6
Fairhurst, Rick M (2007) Transgenic parasites: improving our understanding of innate immunity to malaria. Cell Host Microbe 2:75-6
Guindo, Aldiouma; Fairhurst, Rick M; Doumbo, Ogobara K et al. (2007) X-linked G6PD deficiency protects hemizygous males but not heterozygous females against severe malaria. PLoS Med 4:e66
Oakley, Miranda S M; Kumar, Sanjai; Anantharaman, Vivek et al. (2007) Molecular factors and biochemical pathways induced by febrile temperature in intraerythrocytic Plasmodium falciparum parasites. Infect Immun 75:2012-25
Brittain, Nathaniel J; Erexson, Cindy; Faucette, Lawrence et al. (2007) Non-opsonising aggregates of IgG and complement in haemoglobin C erythrocytes. Br J Haematol 136:491-500