Objectives
Principal Investigators
 . 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
Senior & Staff Scientists
Affiliate Scientists
Collaborations
Core Technologies
Malaria Clinical Trials Center

   
 

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Stefan H. I. Kappe, Ph.D.

Associate Member
Seattle Biomedical Research Institute

Affiliate Associate Professor
Department of Global Health
University of Washington
Email: stefan.kappe@sbri.org

Disease under study: Malaria

Mission
As part of SBRI’s Malaria Program, Dr. Kappe’s work is focused on the biology of malaria parasite mosquito stages and mammalian liver stages. The discovery of pre-erythrocytic subunit vaccine candidates and the creation of whole organism vaccines to prevent malaria infection is a major goal.  Dr. Kappe received a prestigious Grand Challenges in Global Health grant from the Gates Foundation in 2005, targeted at designing genetically engineered, live attenuated Plasmodium falciparum vaccine strains.

Research
The Plasmodium sporozoite stage, which develops in mosquitoes, is transmitted by bite and initiates the infection of the mammalian host. The Kappe Lab has identified numerous proteins that are potentially involved in the invasion process and others that are needed for the establishment of the parasites' intracellular niche and growth in the liver. The function of these proteins is elucidated using genetic, molecular biological and cell biological tools. The lab has recently shown that deletion of genes that encode proteins of the vaculoar compartment surrounding the intra-hepatic liver stage lead to a severe defect in liver stage development.  The lab is also conducting systems biology studies to identify host responses to parasite liver infection.

Immune responses against liver stages confer complete protection against malaria infection yet the antigens involved in this protection have not been identified. Dr. Kappe has analyzed global gene expression in sporozoites and liver stages using microarray and proteomics tools. In collaboration with other investigators at SBRI, he is using these data sets to hung for subunit vaccine candidates.

 

Themes

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Molecular motor that powers malaria parasite motility and invasion

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Gene expression in the malaria sporozoite and liver stage

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Virulence factors mediating productive sporozoite-hepatocyte interactions.

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Liver stage-hepatocyte interactions

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Liver stage vaccine development

Lab Accomplishments

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Identified major components of the malaria parasite molecular invasion machinery

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First large scale gene expression analysis of malaria sporozoites

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Demonstrated differential gene expression in sporozoites during its maturation to fully host-infective forms

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Developed axenic culture system for early liver stages

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First genome-wide gene expression analysis of malaria liver stages

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Development of genetically attenuated sporozoites

The National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation provide support for Dr. Kappe's current research. 

 

 

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