Department / Division:
Medicine / Infectious Diseases

Address:
DUMC 3355
Durham, NC 27710

Appointment Telephone:
919-668-7630

Fax Telephone:
919-479-2948

• MD, Duke University School of Medicine, 1991

• Internal Medicine, Vanderbilt University Medical Center (Tennessee), 1991-1995

• Infectious Diseases, Duke University Medical Center, 1995-1998

Clinical Interests:
Cryptococcal disease, fungal infections, infectious diseases

Research Interests:

The focus of my research is to understand the mechanisms of microbial pathogenesis using the tools of  fungal genetics. I am especially interested in the ways in which microorganisms sense and respond to changes in their environment. For example, as microbial pathogens enter the microenvironment of 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 elucidate signal transduction pathways associated with fungal pathogenicity. This pathogenic fungus displays well-characterized and inducible virulence determinants, and it has other scientifically useful attributes that make it an ideal system for dissecting the signaling pathways associated with pathogenicity .
The main techniques used in the lab are those of molecular genetics. We are now able to readily clone C. neoformans genes and to disrupt them by homologous recombination. Mutant strains with disruptions in targeted genes are then evaluated in vitro for the various mutant phenotypes including altered expression of virulence determinants such as polysaccharide capsule and melanin. The effects of gene disruption on pathogenicity are also evaluated in various animal models of systemic cryptococcal disease. Using these techniques, we have recently identified a novel G-alpha protein/cAMP-dependent signaling pathway associated with mating and pathogenicity in C. neoformans. Several elements of this pathway have now been identified and their roles in pathogenesis are being evaluated.
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
 Cryptococcus neoformans
 Signal transduction
 Fungal mating
 G proteins

Representative Publications:
Vallim MA, Fernandes L, Alspaugh JA. The RAM1 gene encoding a protein-farnesyltransferase {beta}-subunit homologue is essential in Cryptococcus neoformans. Microbiology. 2004 Jun;150(Pt 6):1925-1935. (2004) Abstract

Pukkila-Worley R, Alspaugh JA. Cyclic AMP signaling in Cryptococcus neoformans. FEMS Yeast Res. 2004 Jan;4(4-5):361-7. (2004) 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 Jan;148(Pt 1):191-201. (2002) 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. Eukaryot Cell. 2002 Feb;1(1):75-84. (2002) Abstract

Alspaugh JA, Cavallo LM, Perfect JR, Heitman J. RAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans. Mol Microbiol. 2000 Apr;36(2):352-65. (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 Genet Biol. 1999 Jun;27(1):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 Dev. 1997 Dec 1;11(23):3206-17. (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. Infect Immun. 1991 Jul;59(7):2291-6. (1991) Abstract