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

  • 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

Publications

Alspaugh, JA, Pukkila-Worley, R, Harashima, T, Cavallo, LM, Funnell, D, Cox, GM, Perfect, JR, Kronstad, JW, and Heitman, J. "Adenylyl cyclase functions downstream of the Galpha protein Gpa1 and controls mating and pathogenicity of Cryptococcus neoformans." Eukaryot Cell 1, no. 1 (February 2002): 75-84.

PMID
12455973
Scholars@Duke

Waugh, MS, Nichols, CB, DeCesare, CM, Cox, GM, Heitman, J, and Alspaugh, JA. "Ras1 and Ras2 contribute shared and unique roles in physiology and virulence of Cryptococcus neoformans." Microbiology 148, no. Pt 1 (January 2002): 191-201.

PMID
11782511
Full Text

Yang, Z, Pascon, RC, Alspaugh, JA, Cox, GM, and McCusker, JH. "Molecular and genetic analysis of the Cryptococcus neoformans MET3 gene and a met3 mutant." Microbiology 148, no. 8 (2002): 2617-2625.

Scholars@Duke

Waugh, MS, Nichols, CB, DeCesare, CM, Cox, GM, Heitman, J, and Alspaugh, JA. "Ras1 and Ras2 contribute shared and unique roles in physiology and virulence of Cryptococcus neoformans." Microbiology 148, no. 1 (2002): 191-201.

Scholars@Duke

D'Souza, CA, Alspaugh, JA, Yue, C, Harashima, T, Cox, GM, Perfect, JR, and Heitman, J. "Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans." Mol Cell Biol 21, no. 9 (May 2001): 3179-3191.

PMID
11287622
Full Text

Alspaugh, JA, Cavallo, LM, Perfect, JR, and Heitman, J. "RAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans." Mol Microbiol 36, no. 2 (April 2000): 352-365.

PMID
10792722
Scholars@Duke

Davidson, RC, Cruz, MC, Sia, RA, Allen, B, Alspaugh, JA, and Heitman, J. "Gene disruption by biolistic transformation in serotype D strains of Cryptococcus neoformans." Fungal Genet Biol 29, no. 1 (February 2000): 38-48.

PMID
10779398
Full Text

Alspaugh, JA, Davidson, RC, and Heitman, J. "Morphogenesis of Cryptococcus neoformans." Contrib Microbiol 5 (2000): 217-238. (Review)

PMID
10863675
Scholars@Duke

Yue, C, Cavallo, LM, Alspaugh, JA, Wang, P, Cox, GM, Perfect, JR, and Heitman, J. "The STE12alpha homolog is required for haploid filamentation but largely dispensable for mating and virulence in Cryptococcus neoformans." Genetics 153, no. 4 (December 1999): 1601-1615.

PMID
10581270
Scholars@Duke

Heitman, J, Allen, B, Alspaugh, JA, and Kwon-Chung, KJ. "On the origins of congenic MATalpha and MATa strains of the pathogenic yeast Cryptococcus neoformans." Fungal Genet Biol 28, no. 1 (October 1999): 1-5. (Review)

PMID
10512666
Full Text

Pages