Durham, NC 27710
Cryptococcal disease, fungal infections, infectious diseases
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
This faculty member has no reported relationships with industry.
Pukkila-Worley, R; Alspaugh, JA. Cyclic AMP signaling in Cryptococcus neoformans. FEMS Yeast Research. 2004;4:361-367. (2004) Abstract
Vallim, MA; Fernandes, L; Alspaugh, JA. The RAM1 gene encoding a protein-farnesyltransferase beta-subunit homologue is essential in Cryptococcus neoformans. Microbiology. 2004;150:1925-1935. (2004) Abstract
Alspaugh, JA; Pukkila-Worley, R; Harashima, T; Cavallo, LM; Funnell, D; Cox, GM; Perfect, JR; Kronstad, JW; Heitman, J. Adenylyl cyclase functions downstream of the Galpha protein Gpa1 and controls mating and pathogenicity of Cryptococcus neoformans. Eukaryotic Cell. 2002;1:75-84. (2002) Abstract
Waugh, MS; Nichols, CB; DeCesare, CM; Cox, GM; Heitman, J; Alspaugh, JA. Ras1 and Ras2 contribute shared and unique roles in physiology and virulence of Cryptococcus neoformans. Microbiology. 2002;148:191-201. (2002) Abstract
Alspaugh, JA; Cavallo, LM; Perfect, JR; Heitman, J. RAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans. Molecular Microbiology. 2000;36:352-365. (2000) Abstract
Sudarshan, S; Davidson, RC; Heitman, J; Alspaugh, JA. Molecular analysis of the Cryptococcus neoformans ADE2 gene, a selectable marker for transformation and gene disruption. Fungal Genetics and Biology. 1999;27:36-48. (1999) Abstract
Alspaugh, JA; Perfect, JR; Heitman, J. Cryptococcus neoformans mating and virulence are regulated by the G-protein alpha subunit GPA1 and cAMP. Genes and Development. 1997;11:3206-3217. (1997) Abstract
Alspaugh, JA; Granger, DL. Inhibition of Cryptococcus neoformans replication by nitrogen oxides supports the role of these molecules as effectors of macrophage-mediated cytostasis. Infection and Immunity. 1991;59:2291-2296. (1991) Abstract