Damian J. Krysan, M.D., Ph.D.

First, we have developed a new high throughput screening assay to identify antifungal small molecules that cause yeast cell lysis and are coupling the assay with a chemical genetics approach to identify new cell wall-targeted antifungal small molecules.

Second, we have shown that toremifene, an FDA-approved estrogen antagonist, also is extremely active against Cryptococcus neoformans, an important cause of meningitis in people living with HIV/AIDS. We are currently studying the mechanism of action of toremifene and testing its efficacy in animal models of cryptococcosis. We are also carrying out additional screens for molecules with fungicidal activity against this important pathogen.

Third, we have developed a novel approach to genetic interaction studies in Candida albicans, the most common human pathogen. Using a concept called complex haploinsufficiency, our laboratory, in collaboration with Anuj Kumar's lab at the University of Michigan, has pioneered a method to perform large scale synthetic genetic interaction screens in C. albicans. This approach allows us to map complex genetic regulatory networks. We are currently using this approach to investigate how protein kinase signaling networks regulate C. albicans morphogenesis, a process crucial for virulence.

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