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

Okagaki, Laura H., Yina Wang, Elizabeth R. Ballou, Teresa R. O’Meara, Yong-Sun Bahn, J Andrew Alspaugh, Chaoyang Xue, and Kirsten Nielsen. “Cryptococcal titan cell formation is regulated by G-protein signaling in response to multiple stimuli.” Eukaryot Cell 10, no. 10 (October 2011): 1306–16. https://doi.org/10.1128/EC.05179-11.

PMID
21821718
Full Text

O’Meara, Teresa R., Christie Hay, Michael S. Price, Steve Giles, and J Andrew Alspaugh. “Cryptococcus neoformans histone acetyltransferase Gcn5 regulates fungal adaptation to the host.” Eukaryot Cell 9, no. 8 (August 2010): 1193–1202. https://doi.org/10.1128/EC.00098-10.

PMID
20581290
Full Text

O’Meara, Teresa R., Diana Norton, Michael S. Price, Christie Hay, Meredith F. Clements, Connie B. Nichols, and J Andrew Alspaugh. “Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule.” Plos Pathog 6, no. 2 (February 19, 2010): e1000776. https://doi.org/10.1371/journal.ppat.1000776.

PMID
20174553
Full Text

Ballou, Elizabeth R., Connie B. Nichols, Kathleen J. Miglia, Lukasz Kozubowski, and J Andrew Alspaugh. “Two CDC42 paralogues modulate Cryptococcus neoformans thermotolerance and morphogenesis under host physiological conditions.” Mol Microbiol 75, no. 3 (February 2010): 763–80. https://doi.org/10.1111/j.1365-2958.2009.07019.x.

PMID
20025659
Full Text

Willger, Sven D., Joachim F. Ernst, J Andrew Alspaugh, and Klaus B. Lengeler. “Characterization of the PMT gene family in Cryptococcus neoformans.” Plos One 4, no. 7 (July 27, 2009): e6321. https://doi.org/10.1371/journal.pone.0006321.

PMID
19633715
Full Text

Nichols, Connie B., Jessica Ferreyra, Elizabeth R. Ballou, and J Andrew Alspaugh. “Subcellular localization directs signaling specificity of the Cryptococcus neoformans Ras1 protein.” Eukaryot Cell 8, no. 2 (February 2009): 181–89. https://doi.org/10.1128/EC.00351-08.

PMID
19098128
Full Text

Fortwendel, Jarrod R., Praveen Rao Juvvadi, Nadthanan Pinchai, B Zachary Perfect, J Andrew Alspaugh, John R. Perfect, and William J. Steinbach. “Differential effects of inhibiting chitin and 1,3-{beta}-D-glucan synthesis in ras and calcineurin mutants of Aspergillus fumigatus.” Antimicrob Agents Chemother 53, no. 2 (February 2009): 476–82. https://doi.org/10.1128/AAC.01154-08.

PMID
19015336
Full Text

Price, Michael S., Connie B. Nichols, and J Andrew Alspaugh. “The Cryptococcus neoformans Rho-GDP dissociation inhibitor mediates intracellular survival and virulence.” Infect Immun 76, no. 12 (December 2008): 5729–37. https://doi.org/10.1128/IAI.00896-08.

PMID
18779335
Full Text

Olson, Gillian M., Deborah S. Fox, Ping Wang, J Andrew Alspaugh, and Kent L. Buchanan. “Role of protein O-mannosyltransferase Pmt4 in the morphogenesis and virulence of Cryptococcus neoformans.” Eukaryot Cell 6, no. 2 (February 2007): 222–34. https://doi.org/10.1128/EC.00182-06.

PMID
17142566
Full Text

Nichols, Connie B., Zahra H. Perfect, and J Andrew Alspaugh. “A Ras1-Cdc24 signal transduction pathway mediates thermotolerance in the fungal pathogen Cryptococcus neoformans.” Mol Microbiol 63, no. 4 (February 2007): 1118–30. https://doi.org/10.1111/j.1365-2958.2006.05566.x.

PMID
17233829
Full Text

Pages