Kim C. Williamson
Ph.D. 1987, Boston University
Physiology and Immunology
Malaria is a critical world health problem resulting in 100-200 million clinical cases a year with 2 million deaths, mainly children. Over the last decade the spread of drug-resistant parasites and insecticide-resistant mosquitoes has made the situation worse and the need for new control measures more urgent. At the same time the disease has intensified, advances in recombinant DNA technology have lead to progress in understanding the molecular genetics of the parasites that cause malaria. My work focuses on the sexual/mosquito stages of the parasite, Plasmodium falciparum, that causes the most virulent form of human malaria. Antibodies directed against proteins on the surface of these parasite stages have been shown to preventing the parasites from infecting/colonizing the mosquito, thus blocking malaria transmission.
Ongoing projects in the lab are directed at determining the role of one of the major sexual-stage specific surface proteins, Pfs230, in sexual stage development and malaria transmission-blocking immunity. Molecular approaches such as transfection and targeted-gene disruption are now feasible in this organism and have been used to generate a series of transformants that express distinct regions of Pfs230. These technical advances provide exciting new tools to characterize sexual stage development on the molecular level. Currently the gene expression patterns and ultrastructure of the Pfs230 transformants are being evaluated, as are their ability to infect mosquitoes and evade the immune system.
Future projects include identifying additional genes involved in the transition to sexual stage development and the continued characterization of the trigger and process of gamete emergence from the red blood cell and subsequent fertilization. The generation of transformants that lack or overexpress the genes identified should lead toward the delineation of pathways required for sexual differentiation and transmission to mosquitoes. In addition to elucidating the fundamental biology of this important pathogen this work could lead to novel approaches to control the pathogenesis and transmission of malaria.
López-Barragán, M.J., Lemieux,J., Quiñones, M., Williamson, K.C., Molina-Cruz, A., Cui, K., Barillas-Mury, C., Zhao, K., and Su, X. (2011) Directional gene expression and antisense transcripts in sexual and asexual stages of Plasmodium falciparum. (2011) BMC Genomics 12(1):587-599.
Morahan, B.J., Strobel, C., Hasan, U., Czesny, B., Mantel, P.-Y., Marti, M., Eksi, S. and Williamson, K.C. (2011) Functional Analysis of the Exported Type IV HSP40 Protein PfGECO in Plasmodium falciparum Gametocytes. Eukaryot. Cell 10:1492-1502.
Eksi, S. and Williamson, K.C. (2011) Protein targeting to the parasitophorous vacuole membrane of Plasmodium falciparum. Eukaryot. Cell 10:744-752.
Tanaka, T.Q and Williamson, K.C. (2011) A malaria gametocytocidal assay using oxidoreduction indicator, alamarBlue. Mol. Biochem. Parasitol. 177(2):160-163.
Buchholz, K., Burke, T.A., Williamson, K.C., Wiegand, R.C., Wirth, D.F., Marti, M. (2011) A high throughput screen targeting malaria transmission stages opens new avenues for drug development. J. Infect. Dis. 203:1445-1453.
Rupp, I., Sologub, L., Williamson, K.C., Scheuermayer, M., Reininger, L., Doerig, C., Eksi, S., Kombila, D.U., Frank, M., and Pradel, G. (2011) Malaria parasites form filamentous cell-to-cell connections during reproduction in the mosquito midgut. Cell Res. 21(4):683-696.
Williamson K.C., (2010) Preventing childhood malaria: Strategies that work today and directions for the future. A Child's Right to a Healthy environment. Chap. 2, Ed: James Garbarino, Springer Press, New York, NY
Czesny, B., Goshu, S., Cook J.L. and Williamson, K.C. (2009) Proteasome inhibitor, epoxomicin, has potent P. falciparum gametocytocidal activity. Antimicrob. Agents Chemother. 53: 4080-4085.
Sardá, V., Kaslow, D.C., and Williamson, K.C., (2009) Approaches to malaria vaccine development using the retrospectroscope. Infect. Immun. 77:3130-3140 (Minireveiw & Cover).
Fig. The life cycle of the malaria parasite. When a mosquito takes a bloodmeal, parasites in the form of sporozoites are transmitted to humans. These parasites undergo asexual or sexual differentiation in the host. The mature forms of the parasite can be taken up in a mosquito bloodmeal where they further develop and consequently the cycle of infection perpetuates (Oaks, 1991).