CYSTEINE PROTEINASES AS LEISHMANIAL VIRULENCE FACTORS

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DESCRIPTION (adapted from application abstract): This application is based on the finding that C3H mice develop chronic non-healing lesions when infected with L. mexicana, but mount a strong healing Th1 response to infections caused by L. mexicana lacking the cysteine proteinase b genes (cpb organisms). By characterizing differences in host immune responses to these parasites, it is possible to eliminate confounding genetic variables in host and parasite species. The underlying hypothesis is that cysteine proteinases are involved in suppressing the cell-mediated responses needed for disease cure without engendering a Th2-type response. This is in contrast to the susceptibility of BALB/c mice to L. major, which is Th2-driven. The PI proposes to test the ability of exogenous cysteine proteinases to suppress a healing immune response to L. mexicana and L. major. The project has the potential to help demonstrate that cysteine proteinases are useful targets for vaccine and drug therapies. He will also define the role of cysteine proteinases as virulence factors using inhibitors and transfection methodologies. The candidate has an M.D. and Ph.D. degrees, with thesis research in the GPI anchor of African trypanosomes. He has completed his clinical training in Internal Medicine and a clinical year of Infectious Diseases at the University of Pennsylvania.