Fungal pathogenesis and antifungal drug discovery
The Krysan laboratory is interested in antifungal drug discovery and fungal pathogenesis. We use high throughput screening assays to identify new molecules with activity against Candida and Cryptococcus, two of the most important human fungal pathogens. We then characterize the activity; mechanism of action, and in vivo efficacy using murine models of infection. We are currently focusing on screening multi-drug-resistant Candida, developing acetyl CoA synthetase inhibitors, Hsp90 inhibitors, and identifying the mechanism of action of two new scaffolds.
We also are interested in understanding the transcriptional networks that regulate C. albicans pathogenesis through systematic genetic interaction analysis. Using a large library of transcription factor mutants, we are characterizing the genetic networks required for C. albicans to cause oropharyngeal candidiasis, an important infection for people living with HIV/AIDS. To do so, we are applying a novel in vivo imaging assay that allows us to “watch” C. albicans infections in a mammalian host. The overall goals of this project are to characterize the transcription factors required for virulence within a mammalian host and, hopefully, identify targets and processes that might lead to improved therapies.