Research Interests

FUNGAL PATHOGENESIS 

My current research is focused around understanding the ways in which microorganisms sense and respond to changes in theirexternal environment. Specifically I am interested in Cryptococcus neoformans, an opportunistic fungal pathogen that infects and killsover 200,000 people every year. My thesis work involves evaluating different ways this pathogen senses an increase in extracellular pH using the composition and organization of its plasma membrane. In order to investigate this phenomenon I carried out a large scale mutagenesis screen in order to identify upstream components of a fungal-specific alkaline response pathway, the Rim pathway. The results of my screen identified many membrane-associated proteins that are involved in activating the Rim pathway, including a lipid flippase regulatory subunit: Cdc50. I have identified Cdc50 and its role in maintaining the asymmetry of the plasma membrane as an integral part of Rim pathway activation in that it allows for the localization and function of the putative pH-sensing transmembrane protein of the Rim pathway, Rra1 (Figure 1). I am also interested in how the overall composition of the plasma membrane affects the ability for fungal pathogens to sense changes in external pH. I am currently investigating ways in which basidiomycete-specific proteins of unknown function might be interacting with external changes in acidity and helping the pathogen adapt to increased pH in a Rim-independent manner. I am also interested in how ergosterol specifically plays a role in the integrity of the C. neoformans plasma membrane and pH-sensing.