James Andrew Alspaugh, MD

Professor of Medicine
Professor in Molecular Genetics and Microbiology
Campus mail DUMC Box 102359, 303 Sands Building, Research Drive, Durham, NC 27710
Phone (919) 684-0045
Email address andrew.alspaugh@duke.edu

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

Education and Training

  • M.D., Duke University, 1991

Publications

Alspaugh, JA. "The varied manifestations of disseminated gonococcal infection." J Tenn Med Assoc 87, no. 11 (November 1994): 479-480.

PMID
7983864
Scholars@Duke

GRANGER, DL, BOOCKVAR, KS, POSTON, RM, KURLANDER, RJ, ALSPAUGH, JA, and HIBBS, JB. "ROLE OF NITROGEN-OXIDES IN HOST-DEFENSE AGAINST INTRACELLULAR PATHOGENS." 1993.

Scholars@Duke

Alspaugh, JA, and Granger, DL. "Inhibition of Cryptococcus neoformans replication by nitrogen oxides supports the role of these molecules as effectors of macrophage-mediated cytostasis." Infect Immun 59, no. 7 (July 1991): 2291-2296.

PMID
2050398
Scholars@Duke

GRANGER, DL, ALSPAUGH, JA, CAMERON, ML, and HIBBS, JB. "ROLE OF MACROPHAGE NITROGEN OXIDATION METABOLISM AS AN ANTIMICROBIAL HOST DEFENSE-MECHANISM." 1991.

Scholars@Duke

Skrzynia, C, Binninger, DM, Alspaugh, JA, and Pukkila, PJ. "Molecular characterization of TRP1, a gene coding for tryptophan synthetase in the basidiomycete Coprinus cinereus." Gene 81, no. 1 (September 1, 1989): 73-82.

PMID
2806911
Scholars@Duke

Pages