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Joseph D. Smith, Ph.D.
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Associate Member
Seattle Biomedical Research Institute
Associate Director, Malaria Program
Email: joseph.smith@sbri.org
Disease under study:
Malaria
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Mission
As part of the global initiative to fight malaria, SBRI is using innovative strategies and advanced technologies to investigate the malaria parasite. Launched by a $5 million grant from the Bill & Melinda Gates foundation, SBRI recruited malaria scientists and initiated a combination of research and clinical studies towards the development of malaria vaccines.
Research
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.
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Themes |
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Cytoadherence of infected erythrocytes |
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Pregnancy malaria |
Lab Accomplishments |
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Developed binding assays and
computational approaches to investigate the parasite cytoadherent
receptors responsible for infected erythrocyte sequestration and
disease. |
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Inter-isolante var gene comparisons and
genome-wide binding comparisons. |
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Characterized PfEMP1 protein involved in
placental binding that is being developed as a vaccine for malaria
during pregnancy. |
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Dr. Smith's current research is currently supported by the National Institutes of Health (NIH).
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