The Krysan lab is interested in understanding how pathogenic fungi cause disease; how the host defends itself against these fungal pathogens; and how to develop new therapies for human fungal diseases. We use a combination of genetic, chemical-genetic, cell biological, and biochemical methods to investigate questions related to these topics. Currently, we are focused on three human fungal pathogens: Candida albicans, the most common human fungal pathogen; Cryptococcus neoformans, the most important cause of life-threatening fungal disease in those living with HIV/AIDS; and Aspergillus fumigatus, an important cause of mold infections in a range of patient populations. We have recently developed a set of genetic tools to probe the transcriptional networks that allow C. albicans to cause mucosal disease. In collaboration with Dr. Melanie Wellington, we are combining these tools with novel methods to directly image and assess C. albicans infections in mammals using confocal microscopy. Also, in collaboration with Dr. Wellington, we are investigating the role of the cytokines IL-1alpha/beta in the host response to C. albicans. Finally, we use high throughput screening approaches to identify novel antifungal small molecules. Highly active molecules are then evaluated in a pipeline of pre-clinical testing that leads to initial in vivo efficacy studies in mammalian models of candidiasis and cryptococcosis. Recently, our work has led to the initiation of a Phase II clinical trial to test the ability of tamoxifen to improve current therapy of cryptococcal meningitis in HIV/AIDS patients (NCT03112031).