SBRI - Research: Scientists

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.	Ian Nicholas Crispe

.	Patrick Duffy


.	Michal Fried

.	Malcolm Gardner

.	Christoph Grundner
.	Helen Horton

.	Stefan Kappe

.	Peter Myler

.	Marilyn Parsons

.	David Sherman

.	Joseph Smith

.	Don Sodora

.	Leonidas Stamatatos

.	Ken Stuart

.	Ruobing Wang

.	Theodore White

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Joseph D. Smith, Ph.D.

		Associate Member Seattle Biomedical Research Institute Associate Director, Malaria Program Research Assistant Professor Department of Global Health University of Washington Email: joseph.smith@sbri.org Disease under study: Malaria

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.

Themes
*	Cytoadherence of infected erythrocytes
*	Pregnancy malaria

Lab Accomplishments
*	Developed binding assays and computational approaches to investigate the parasite cytoadherent receptors responsible for infected erythrocyte sequestration and disease.
*	Inter-isolante var gene comparisons and genome-wide binding comparisons.
*	Characterized PfEMP1 protein involved in placental binding that is being developed as a vaccine for malaria during pregnancy.

Dr. Smith's current research is supported by the National Institutes of Health (NIH).

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