HOST-PATHOGEN INTERACTIONS: RESOLVING MECHANISMS OF
FUNGAL DISSEMINATION TO THE CNS.
The Gelli Lab studies the pathogenesis of human fungal pathogens with a particular focus on fungi that disseminate to the central nervous system (CNS). Among the pathogens we study is Cryptococcus neoformans – the leading cause of fungal meningoencephalitis. Our studies are aimed at resolving the molecular mechanisms mediating the interplay between fungi and the CNS. This interest was spearheaded in part by our study of the extracellular proteome of C. neoformans, where we identified a key fungal protease that promotes fungal disease in the CNS. Current studies include translation of our basic research to develop anti-virulence drugs via drug screens aimed at blocking protease activity and developing a platform technology that will deliver therapeutic drugs across the blood-brain barrier by conjugating the protease to drug-loaded nanocarriers.
Our current research efforts include collaborative studies aimed at the characterization of a similar protease in the pulmonary-to-CNS dissemination of Coccidioides, the cause of Valley Fever throughout the Southwestern United States, and a novel diagnostic tool that would differentiate a pulmonary cancer nodule from a fungal nodule.
Our interest in the blood-brain barrier during pathological conditions has resulted in a collaborative study aimed at understanding how endothelial cell senescence during aging alters blood-brain barrier function and how that impacts the onset of dementia.