Genetics of Drug Resistance, Antigenic Variation and Dis

Wellems, Thomas E.

Abstract

The Malaria Genetics Section of the Laboratory of Parasitic Diseases focuses on Plasmodium falciparum, the parasite that causes the most severe form of human malaria. Our research includes the following projects: * Identification and characterization of the factors involved in responses to such major antimalarial drugs as chloroquine and quinine. * Mapping of loci that determine P. falciparum infectivity in the Aotus malaria model. * Dissection of the gene controls that regulate expression of var genes responsible for antigenic variation and evasion of the host immune system. * Field and laboratory investigations of the protection conferred by hemoglobins C and S against the severe forms of falciparum malaria. The work in these projects incorporates strategies of linkage mapping, population surveys, gene manipulation, and gene product analysis. The findings provide fundamental biological information for the development of diagnostics, therapeutics, and control measures against the disease.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000483-16
• Application #: 6503186
• Study Section: (LPD)
• Support Year: 16
• Fiscal Year: 2001

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

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