Regulation of G-Protein Signaling in C. neoformans - Previous studies have shown that there are two parallel G-protein signaling pathways functioning in the pathogenic fungus C. neoformans. Our research focuses on regulators of G-protein signaling, such as Crg1, that modulate G-protein signaling. Our long-term goals are to understand how C. neoformans cells sense and respond to signals that coordinate their growth and differentiation, to reveal the relationships between signaling pathways and pathogenesis, and to discover novel antifungal targets.

Signaling of C. neoformans Sch9 Kinase in survival of macrophages and virulence - Polysaccharide capsule formation is one of the established virulence factors in C. neoformans. Our previous studies have shown that an Sch9 protein kinase homolog controls capsule formation and virulence in conjunction with the Gpa1-PKA signaling pathway in C. neoformans. We are interested in exploring the mechanism by which Sch9 acts in capsule formation and virulence, and plan to employ an in vitro macrophage survival model to examine how Sch9 is activated and its genetic interactions with signaling pathways important in mating, capsule formation and virulence. Our goals are to understand how Sch9 signals in an intracellular environment that will lead to better understanding of how fungal pathogens such as C. neoformans circumvent the host's immune system to cause disease.

Functions of Cyclophilin Cpa1 and Cpa2 - C. neoformans Cpa1 and Cpa2 are cyclophilins that are important for growth and virulence. Cpa1, in particular, is required for growth at 39°C. To further study functions of Cpa1, we have employed a yeast two-hybrid screen to identify proteins that interact with Cpa1. Our ongoing efforts to functionally characterize proteins, including sucrose invertase and trahalose phosphatase, that interact with Cpa1, will allow us to test the hypothesis that Cpa1 plays a role in regulating carbohydrate metabolism in the fungus.