Kirsten Nielsen

Cryptococcus neoformans is a ubiquitous pathogenic yeast and the causative agent of the respiratory disease cryptococcosis, which disproportionately affects immunocompromised populations including cancer chemotherapy and organ transplant recipients, as well as individuals living with advanced HIV. In severe cases, pulmonary cryptococcus may disseminate to the central nervous system causing severe and often fatal crytococcal meningitis. 

A hallmark of cryptococcal pathogenesis is the ability to produce enlarged, polyploid cells known as titan cells during pumonary infection, which endow their euploid or aneuploid progeny with enhanced virulence traits including heightened resistance to immune cell clearance, increased antifungal tolerance and heteroresistance, and genetic heterogeneity. In addition, clinical isolates of C. neoformans have been shown to cause a continuum of disease outcomes ranging from controlled latent infections that are contained within pulmonary granulomas, lethal disease, and hypervirulant infections marked by rapid mortality. 

Research in the Nielsen lab explores several facets of C. neoformans biology including the genetic and cellular mechanisms underlying the generation of titan cells and their progeny, the host-pathogen interactions that drive latent, lethal, and hypervirulent disease outcomes, and the propensities of C. neoformans clinical isolates to exhibit baseline and stress-associated acquisition of antifungal tolerance and hetroresistance. To answer our research questions, we employ diverse cell and molecular biology techniques, immunology, in vivo mouse models of infection, bioinformatics, and more.