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

Selvig, K, Ballou, ER, Nichols, CB, and Alspaugh, JA. "Restricted substrate specificity for the geranylgeranyltransferase-I enzyme in Cryptococcus neoformans: implications for virulence." Eukaryotic Cell 12, no. 11 (November 2013): 1462-1471.

PMID
24014765
Full Text

Ballou, ER, Selvig, K, Narloch, JL, Nichols, CB, and Alspaugh, JA. "Two Rac paralogs regulate polarized growth in the human fungal pathogen Cryptococcus neoformans." Fungal Genet Biol 57 (August 2013): 58-75.

PMID
23748012
Full Text

O'Meara, TR, Holmer, SM, Selvig, K, Dietrich, F, and Alspaugh, JA. "Cryptococcus neoformans Rim101 is associated with cell wall remodeling and evasion of the host immune responses." Mbio 4, no. 1 (January 15, 2013).

PMID
23322637
Full Text

Ballou, ER, Kozubowski, L, Nichols, CB, and Alspaugh, JA. "Ras1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen Cryptococcus neoformans." Plos Genetics 9, no. 8 (January 2013): e1003687-null.

PMID
23950731
Full Text

Ballou, ER, Selvig, K, Narloch, JL, Nichols, CB, and Alspaugh, JA. "Two Rac paralogs regulate polarized growth in the human fungal pathogen Cryptococcus neoformans." Fungal Genetics and Biology 57 (2013): 58-75.

Full Text

O'Meara, TR, and Alspaugh, JA. "The Cryptococcus neoformans capsule: a sword and a shield." Clinical Microbiology Reviews 25, no. 3 (July 2012): 387-408. (Review)

PMID
22763631
Full Text

Shen, G, Zhou, E, Alspaugh, JA, and Wang, P. "Wsp1 is downstream of Cin1 and regulates vesicle transport and actin cytoskeleton as an effector of Cdc42 and Rac1 in Cryptococcus neoformans." Eukaryotic Cell 11, no. 4 (April 2012): 471-481.

PMID
22327008
Full Text

Ballou, ER, Alspaugh, JA, and Nichols, CB. "Morphogenesis of Cryptococcus neoformans." Topics in Current Genetics 22 (2012): 197-223.

Full Text

Selvig, K, and Alspaugh, JA. "pH Response Pathways in Fungi: Adapting to Host-derived and Environmental Signals." Mycobiology 39, no. 4 (December 7, 2011): 249-256.

PMID
22783112
Full Text

Hast, MA, Nichols, CB, Armstrong, SM, Kelly, SM, Hellinga, HW, Alspaugh, JA, and Beese, LS. "Structures of Cryptococcus neoformans protein farnesyltransferase reveal strategies for developing inhibitors that target fungal pathogens." J Biol Chem 286, no. 40 (October 7, 2011): 35149-35162.

PMID
21816822
Full Text

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