Genetics Of Drug Resistance, Antigenic Variation And Dis

Wellems, Thomas E.

Abstract

Our research program focuses on four subject areas: [1] drug resistance of malaria parasites and the factors that affect clinical outcomes after antimalarial treatment; [2] the means by which malaria parasites avoid human immune defenses; [3] why strains of the most deadly malaria parasite (Plasmodium falciparum) show different infectivities to the cells of humans and other primates; and [4] the nature of protection against malaria that is conferred to children by such hemoglobin mutations as HbC and HbS (sickle-cell). In each of these areas we seek research advances that can improve the knowledge of disease processes in malaria and thereby support the development of new antimalarial chemotherapies, diagnostic tools, and vaccines. The research activities in our program are multidisciplinary and include field studies in malarious regions as well as programs of laboratory investigation on the NIH campus.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000483-18
• Application #: 6808181
• Study Section: (LMVR)
• Support Year: 18
• Fiscal Year: 2003

Institution

• Name: Niaid Extramural Activities
• Country: United States

Publications

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

Hayton, Karen; Gaur, Deepak; Liu, Anna et al. (2008) Erythrocyte binding protein PfRH5 polymorphisms determine species-specific pathways of Plasmodium falciparum invasion. Cell Host Microbe 4:40-51

Su, Xinzhuan; Hayton, Karen; Wellems, Thomas E (2007) Genetic linkage and association analyses for trait mapping in Plasmodium falciparum. Nat Rev Genet 8:497-506

Djimde, A A; Kirkman, L; Kassambara, L et al. (2007) [In vitro cultivation of fields isolates of Plasmodium falciparum in Mali] Bull Soc Pathol Exot 100:3-5

Sa, Juliana Martha; Yamamoto, Marcio M; Fernandez-Becerra, Carmen et al. (2006) Expression and function of pvcrt-o, a Plasmodium vivax ortholog of pfcrt, in Plasmodium falciparum and Dictyostelium discoideum. Mol Biochem Parasitol 150:219-28

Fairhurst, Rick M; Wellems, Thomas E (2006) Modulation of malaria virulence by determinants of Plasmodium falciparum erythrocyte membrane protein-1 display. Curr Opin Hematol 13:124-30

Rohrbach, Petra; Sanchez, Cecilia P; Hayton, Karen et al. (2006) Genetic linkage of pfmdr1 with food vacuolar solute import in Plasmodium falciparum. EMBO J 25:3000-11

Diallo, Dapa A; Doumbo, Ogobara K; Plowe, Christopher V et al. (2005) Community permission for medical research in developing countries. Clin Infect Dis 41:255-9

Cooper, Roland A; Papakrivos, Janni; Lane, Kristin D et al. (2005) PfCG2, a Plasmodium falciparum protein peripherally associated with the parasitophorous vacuolar membrane, is expressed in the period of maximum hemoglobin uptake and digestion by trophozoites. Mol Biochem Parasitol 144:167-76

Arie, Takayuki; Fairhurst, Rick M; Brittain, Nathaniel J et al. (2005) Hemoglobin C modulates the surface topography of Plasmodium falciparum-infected erythrocytes. J Struct Biol 150:163-9