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Associate Member Disease under study: Malaria |
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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.
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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 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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©2009 Seattle Biomedical Research Institute. All rights reserved. SBRI is a 501(c)3 not-for-profit organization. info@sbri.org |
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