J. Andrew Alspaugh, MD
- Medicine / Medicine-Infectious Diseases
- Molecular Genetics and Microbiology
Address
DUMC 102359
Durham, NC 27710
Appointment Telephone
919-668-7630
Office Telephone
919-684-4335
Fax Telephone
919-684-8902
- 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 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
Cryptococcus neoformans
Signal transduction
Fungal mating
G proteins
This physician has no reported relationships with industry.
Representative Publications
Pukkila-Worley R, Alspaugh JA. Cyclic AMP signaling in Cryptococcus neoformans. FEMS Yeast Res. 2004 Jan;4(4-5):361-7.
(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 Jun;150(Pt 6):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. Eukaryot Cell. 2002 Feb;1(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 Jan;148(Pt 1):191-201.
(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
