Seattle Biomedical Research Institute307 Westlake Ave. N., Suite 500Seattle, WA 98109-5219
Dr. Smith’s research on Plasmodium falciparum seeks to understand the processes of antigenic variation and cytoadherence, key factors in parasite immune evasion and a virulence determinant for the parasite. During the blood stage development, P. falciparum parasites export cytoadhesive proteins to the infected erythrocyte surface that allow infected erythrocytes to sequester from blood circulation. This process allows parasites to avoid spleen-dependent killing mechanisms, but can lead to severe disease complications when infected erythrocytes accumulate in brain or placental blood vessels.
The parasite proteins involved in infected erythrocyte sequestration are called P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 proteins are encoded by approximately 60 var genes per parasite isolate, but are expressed in a mutually exclusive fashion. Switching between var genes allows the parasite to evade immune destruction and sequester at different sites in the body.
Dr. Smith’s lab is studying the binding properties and genetic diversity of PfEMP1 proteins, in order to develop interventions that can prevent malaria disease complications.
Another project in the lab is to apply immunogen design approaches to elicit antibodies that inhibit parasite invasion of erythrocytes.
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Fred Hutchison Cancer Research Center | University of Washington
Institute for Systems Biology | Seattle Biomed