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Vandana Thathy
kilifi [dot] kemri-wellcome [dot] org Research
The deadliest human malaria parasite, Plasmodium falciparum, infects red blood cells during part of its lifecycle, producing the symptoms of malaria. During this stage, the parasite inserts proteins known as variant surface antigens (VSA) onto the surface of the infected red cells. A buildup of immunity to these proteins is important to the development of protection from P. falciparum malaria in endemic populations. Host immune pressure is thought to drive the extensive sequence variability observed in VSA and is reflected by the amplification of genes encoding these antigens into large, diverse families in the parasite's genome. At present, a single family of VSA, P. falciparum erythrocyte membrane protein (PfEMP)1, encoded by the var genes, is known to play a key role in pathogenesis and immunity, and forms a major candidate target of naturally acquired protective antibodies that recognize the infected red cell surface. However, other VSA families, including RIFIN and STEVOR, which undergo antigenic variation and are expressed on the infected red cell surface, may also serve important roles in pathogenesis and immunity. Our group's current research focuses on whether the immune system recognizes RIFIN and/or STEVOR and produces effective antibodies against these antigens that help prevent future disease. We are also characterizing their diversity in a natural population of P. falciparum from coastal Kenya. The knowledge gained will expand our current understanding of antigenic variation in P. falciparum and help to better define the targets of naturally acquired protective antibody responses against malaria.
Collaborations
Publications
Bull, P.C., Buckee, C.O., Kyes, S., Kortok, M.M., Thathy, V., Guyah, B., Stoute, J.A., Newbold, C.I., Marsh, K. (2008) Plasmodium falciparum antigenic variation. Mapping mosaic var gene sequences onto a network of shared, highly polymorphic sequence blocks. Mol. Microbiol. 68:1519-34.
Jongco, A.M., Ting, L.M., Thathy, V., Mota, M.M., and Kim, K. (2006) Improved transfection and new selectable markers for the rodent malaria parasite Plasmodium yoelii. Mol. Biochem. Parasitol. 146: 242-250.
Thathy, V., Moulds, J.M., Guyah, B., Otieno, W., and Stoute, J.A. (2005) Complement receptor 1 polymorphisms associated with resistance to severe malaria in Kenya. Malar. J. 4: 54.
Miller, S.A., Thathy, V., Ajioka, J.W., Blackman, M.J., and Kim, K. (2003) TgSUB2 is a Toxoplasma gondii rhoptry organelle processing proteinase. Mol. Microbiol. 49: 883-894.
Thathy, V., and Ménard, R. (2002) Gene targeting in Plasmodium berghei. Methods in Molecular Medicine, Malaria Methods and Protocols, Humana, Totowa, NJ 72: 317-331.
Thathy, V., Fujioka, H., Gantt, S., Nussenzweig, R., Nussenzweig, V., and Ménard, R. (2002) Levels of circumsporozoite protein in the Plasmodium oocyst determine sporozoite morphology. EMBO J. 21: 1586-1596.
Mota, M.M., Thathy, V., and Nussenzweig, V. (2001) Stable transformation and gene targeting of Plasmodium yoelii. Mol. Biochem. Parasitol. 113: 271-278.
Natarajan, R., Thathy, V., Mota, M.M., Hafalla, J.C.R., Ménard, R., and Vernick, K.D. (2001) Fluorescent Plasmodium berghei pre-erythrocytic stages: a new tool to study mosquito-mammalian host-parasite interactions. Cell Microbiol. 3: 371-379.
Sultan, A.A., Thathy, V., de-Koning Ward, T.F., Ménard, R., and Nussenzweig, V. (2001) Complementation of Plasmodium berghei TRAP knock-out parasites using human dihydrofolate reductase gene as a second selectable marker. Mol. Biochem. Parasitol. 113: 151-156.
de Koning-Ward, T.F., Fidock, D.A., Thathy, V., Ménard, R., van Spaendonk, R.M., Waters, A.P., and Janse, C.J. (2000) The selectable marker human dihydrofolate reductase enables sequential genetic manipulation of the Plasmodium berghei genome. Mol. Biochem. Parasitol. 106: 199-212.
Sultan, A.A., Thathy, V., Nussenzweig, V., and Ménard, R. (1999) Green fluorescent protein as a marker in Plasmodium berghei transformation. Infect. Immun. 67: 2602-2606.
Nunes, A., Thathy, V., Bruderer, T., Sultan, A.A., Nussenzweig, R., and Ménard, R. (1999) Subtle mutagenesis by ends-in recombination in malaria parasites. Mol. Cell. Biol. 19: 2895-2902.
Sultan, A.A., Thathy, V., Frevert, U., Robson, K.J.H., Crisanti, A., Nussenzweig, V., Nussenzweig, R.S., and Ménard, R. (1997) TRAP is necessary for gliding motility and infectivity of Plasmodium sporozoites. Cell 90: 511-522.
Severson, D.W., Thathy, V., Mori, A., Zhang, W., and Christensen, B.M. (1995) RFLP mapping of quantitative trait loci for malaria parasite susceptibility in the mosquito Aedes aegypti. Genetics 139: 1711-1717.
Thathy, V., Severson, D.W., and Christensen, B.M. (1994) Reinterpretation of the genetics of susceptibility of Aedes aegypti to Plasmodium gallinaceum. J. Parasitol. 80: 705-712