The focus of my research is to understand the ways in which microorganisms sense and respond to changes in their environment. As microbial pathogens enter the infected host, dramatic genetic and phenotypic events occur that allow these organisms to survive in this harsh environment. We study the model fungal organism Cryptococcus neoformans to define signal transduction pathways associated with systemic fungal diseases. This pathogenic fungus causes lethal infections of the central nervous system in patients with AIDS and other immunological disorders. In addition to being an important pathogen, C. neoformans displays well-characterized and inducible virulence determinants. It is an outstanding system for dissecting the signaling pathways associated with pathogenicity.
The main techniques used in the lab are those of molecular genetics. We are able to readily mutate C. neoformans genes by homologous recombination. Mutant strains with disruptions in targeted genes are then evaluated in vitro for various phenotypes including altered expression of polysaccharide capsule and melanin. The effects of gene disruption on pathogenicity are also evaluated in animal models of cryptococcal disease. Using these techniques, we have identified a novel G-alpha protein/cAMP-dependent signaling pathway associated with mating and pathogenicity.
This research is complemented by the other investigators in the Duke University Mycology Research Unit. The members of this research community are pursuing studies in fungal pathogenesis, identifying novel antifungal drug targets, and studying the ecology of several medically important fungi.
Keywords: Microbial Pathogenesis
Education and Training
- Fellow, Infectious Diseases, Duke University School of Medicine, 1995 - 1998
- Resident, Medicine, Vanderbilt University, School of Medicine, 1992 - 1995
- Intern, Medicine, Vanderbilt University, School of Medicine, 1991 - 1992
- M.D., Duke University, 1991
- Interdisciplinary Research Training Program in AIDS
- Genetic and Genomics Training Grant
- Molecular Mycology and Pathogenesis Training Program
- Transplant Infectious Diseases Interdisciplinary Research Training Grant (TIDIRTG)
- Duke Physician Scientist Development program
- Metal Homeostasis in Yeast
- Deciphering the principles of selective recognition of complex RNAs by small molecules
- Duke Resident Physician-Scientist Program - NIAID
- Role of osteopontin in innate immunity during infections and inflammation
- Defining pH-Sensing in Fungal Virulence (F31)
- Coordinated Regulation of Virulence Genes in C. neoformans