Cryptococcus neoformans is a human pathogenic fungus that causes life-threatening meningoencephalitis in immunocompromised individuals. One important aspect of cryptococcosis is the ability of C. neoformans cells to cross the blood-brain barrier. While the processes involved in central nervous system (CNS) penetration have been elucidated over the past few years, the methods by which C. neoformans induces these processes are unknown.
These researchers are testing the hypothesis that alterations in gene expression play a central role in C. neoformans entry into the CNS by affecting the interaction of C. neoformans with the blood-brain barrier. They are testing this hypothesis by monitoring and perturbing in vivo gene expression using mutant strains. The response of the host and svirulence of mutant strains are being examined to identify downstream targets of signaling pathways by microarray, RNAseq, and WGS analysis. This information will then be used to examine changes in cellular traits that affect CNS entry. These studies will allow the identification of key components of CNS penetration by Cryptococcus and provide a foundation for treatment strategies designed to reduce CNS penetration to alleviate disease symptoms and allow for increased exposure to antifungal drugs.
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