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Stefan H. I. Kappe, Ph.D.
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Associate Member
Seattle Biomedical Research Institute
Malaria Program, investigating potential targets for malaria vaccine
Email: stefan.kappe@sbri.org
Disease under study:
Malaria
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Mission
As part of SBRI’s Malaria Antigen Discovery (MAD) Program, Dr. Kappe’s work is centered on the biology of malaria mosquito stages and mammalian liver stages. The discovery of
pre-erythrocytic subunit vaccine candidates and the creation of genetically attenuated parasites as whole organism vaccines to prevent malaria infection is a major goal.
In 2005, Dr. Kappe received one of 43 prestigious Grand Challenges in Global
Health grants from the Gates Foundation, targeted at identifying the immune
responses that prevent severe disease and death due to Plasmodium falciparum
malaria.
Research
The Kappe laboratory is interested in the Plasmodium sporozoite stage, which develops in mosquitoes, is transmitted by bite and initiates the infection of the mammalian host. Sporozoites develop in the midgut of an infected mosquito, are released into the mosquito body cavity and subsequently invade the mosquito salivary glands. Here they accumulate in significant numbers to be transmitted during the next bite. After transmission, sporozoites actively invade hepatocytes and transform into intracellular liver stages. Liver stages rapidly grow and differentiate into thousands of red blood cell-infectious
merozoites. The lab has identified numerous proteins that are potentially involved in the invasion process and others that are needed for the establishment and growth of the liver stage. The function of these proteins is elucidated using genetic, molecular biological and cell biological tools. We have recently disrupted genes that encode proteins of the vacuolar compartment surrounding the intra-hepatic liver stage. Parasites lacking these proteins show a severe defect in liver stage development.
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 is now embarking on the challenging task of analyzing gene expression in liver stages using microarray and proteomics tools.
| 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
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| 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
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First genome-wide gene expression analysis of malaria liver stages |
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Development of genetically attenuated sporozoites |
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The
National Institutes of Health (NIH) and the Bill
& Melinda Gates Foundation provide support
for Dr. Kappe's current research.
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