SEMINAR CANCELLED

This seminar has been cancelled.

Invasive fungal disease (IFD) is estimated to cause more deaths than either tuberculosis or malaria. The ubiquitous soil-associated fungus Cryptococcus neoformans is the leading cause of mortality due to IFD. Infection with C. neoformans begins with pneumonia and may progress to life-threatening meningitis. C. neoformans infects a wide spectrum of patients ranging from apparently healthy individuals to those with defective immunity, yet the determinants of which exposed individuals will ultimately develop disease are poorly understood. Furthermore, among individuals with established C. neoformans disease there is broad variation in clinical progression and responses to therapy. Inbred mouse strains also exhibit significant differences in host resistance against experimental pulmonary infection with C. neoformans. Using forward genetic analysis and construction of congenic/sub-congenic mouse strains, we have identified and validated the biological role of two susceptibility loci that regulate the host response to C. neoformans pneumonia. We aim to identify candidate genes that underlie the differential resistance phenotype using immune profiling in the lung in combination with comparative sequence and expression analysis of effector cell populations. Our overall research aim is to discover the mechanisms that regulate permissive versus protective host responses and use this knowledge to identify prognostic biomarkers and ultimately to develop personalized therapeutics to promote durable and appropriately regulated protective immunity.