Host-pathogen interactions during fungal pathogenesis
Fungal infections are often a harbinger of imminent death, yet few drugs exist to treat them. Cryptococcus neoformans is responsible for 1 million new infections annually in immunocompromised individuals, most of which result in death due to meningitis. This makes it among the most successful opportunistic pathogens of humans. We seek to understand the molecular underpinnings of this unusual success. As the only human pathogenic fungus with a complete sexual cycle and haploid genetics, this budding yeast offers unique experimental advantages. We implemented the first large-scale genetic screens to identify genes required fitness in the mammalian host. These studies led to the identification of transcriptional regulators required for virulence including two GATA family regulators and downstream secreted proteins that control the ability of Cryptococcus to resistant phagocytosis. Remarkably, this program is independent of the polysaccharide capsule of C. neoformans, previously thought to be the major antiphagocytic mechanism. We are investigating this central virulence regulatory network and its downstream effectors using cutting-edge approaches to uncover the key pathogen strategies that mediate its success. We are also making significant investments to develop tools that we anticipate will further accelerate progress towards understanding this important pathogen.