The Malaria Genetics Section of the Laboratory of Parasitic Diseases conducts basic research on factors that govern the drug response, pathogenesis and transmission of malaria. The work incorporates strategies of linkage mapping, field population surveys, gene manipulation and gene product analysis with a view toward the discovery of fundamental biological information that will be of use in the development of new diagnostics, therapeutics and control measures against the disease. The research of the section largely focuses upon Plasmodium falciparum, the parasite that causes the most severe form of malaria and produces 2-3 million deaths each year from the disease. Current projects include investigations of 1) molecular mechanisms of drug resistance, particularly the resistance of malaria strains to such crucial anti-parasite drugs as chloroquine, quinine, and mefloquine; 2) gene transcription switches and DNA recombination events responsible for the antigenic variation and immune evasion of parasitized red blood cells; 3) epidemiology of hemoglobins C and S (sickle-cell) and their protection against severe malaria in African children; 4) a genetic defect in chromosome 12 that adversely affects the development of male gametocytes. - malaria; drug resistance; antigenic variation; hemoglobins; sickle-cell; chloroquine; quinine; mefloquine; genetics; genomics - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000483-14
Application #
6288856
Study Section
Special Emphasis Panel (LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
1999
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
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
Sa, Juliana Martha; Nomura, Takashi; Neves, Joana d'Arc et al. (2005) Plasmodium vivax: allele variants of the mdr1 gene do not associate with chloroquine resistance among isolates from Brazil, Papua, and monkey-adapted strains. Exp Parasitol 109:256-9
Furuya, Tetsuya; Mu, Jianbing; Hayton, Karen et al. (2005) Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis. Proc Natl Acad Sci U S A 102:16813-8
Wang, Xinhua; Mu, Jianbing; Li, Guoqiao et al. (2005) Decreased prevalence of the Plasmodium falciparum chloroquine resistance transporter 76T marker associated with cessation of chloroquine use against P. falciparum malaria in Hainan, People's Republic of China. Am J Trop Med Hyg 72:410-4

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