My lab focuses on the major human fungal pathogen Cryptococcus neoformans, which kills an estimated 600,000 people each year. One of the key aspects of C. neoformans pathogenesis is proliferation and dissemination from the lungs to the brain, where the fungus causes meningitis. During growth in the lung, Cryptococcus undergoes an unusual morphological transition from haploid yeast to highly polyploid Titan cells. Titan cells are associated with dissemination to the brain and a non-protective TH2 response. Despite their important role in pathogenesis, until recently we were unable to study these cells in vitro. My lab have developed a robust assay for the rapid generation of these cells in vitro and are now working to address the questions of how these cells form, what the physiologically relevant triggers are, and how they influence disease outcome. In particular, we are studying how host (ROS/RNS) and environmental (bacterial cell wall) factors together drive this morphological transition using cell biological, molecular, and genetic approaches. Our data begin to reveal fundamental cross-kingdom signals that drive fungal morphogenesis and pathogenesis.