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

Perlatti, Bruno, Connie B. Nichols, J Andrew Alspaugh, James B. Gloer, and Gerald F. Bills. “Sphaerostilbellins, New Antimicrobial Aminolipopeptide Peptaibiotics from Sphaerostilbella toxica.” Biomolecules 10, no. 10 (September 26, 2020). https://doi.org/10.3390/biom10101371.

PMID
32993102
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Perlatti, Bruno, Guy Harris, Connie B. Nichols, Dulamini I. Ekanayake, J Andrew Alspaugh, James B. Gloer, and Gerald F. Bills. “Campafungins: Inhibitors of Candida albicans and Cryptococcus neoformans Hyphal Growth.” J Nat Prod 83, no. 9 (September 25, 2020): 2718–26. https://doi.org/10.1021/acs.jnatprod.0c00641.

PMID
32881504
Full Text

Oliveira, Fabiana Freire M., Hugo Costa Paes, Luísa Defranco F. Peconick, Fernanda L. Fonseca, Clara Luna Freitas Marina, Anamélia Lorenzetti Bocca, Mauricio Homem-de-Mello, et al. “Erg6 affects membrane composition and virulence of the human fungal pathogen Cryptococcus neoformans.” Fungal Genet Biol 140 (July 2020): 103368. https://doi.org/10.1016/j.fgb.2020.103368.

PMID
32201128
Full Text

Brown, Hannah E., Calla L. Telzrow, Joseph W. Saelens, Larissa Fernandes, and J Andrew Alspaugh. “Sterol-Response Pathways Mediate Alkaline Survival in Diverse Fungi.” Mbio 11, no. 3 (June 16, 2020). https://doi.org/10.1128/mBio.00719-20.

PMID
32546619
Full Text

Gusa, Asiya, Jonathan D. Williams, Jang-Eun Cho, Anna Floyd Averette, Sheng Sun, Eva Mei Shouse, Joseph Heitman, J Andrew Alspaugh, and Sue Jinks-Robertson. “Transposon mobilization in the human fungal pathogen Cryptococcus is mutagenic during infection and promotes drug resistance in vitro.” Proc Natl Acad Sci U S A 117, no. 18 (May 5, 2020): 9973–80. https://doi.org/10.1073/pnas.2001451117.

PMID
32303657
Full Text

Trevijano-Contador, Nuria, Kaila M. Pianalto, Connie B. Nichols, Oscar Zaragoza, J Andrew Alspaugh, and Liise-Anne Pirofski. “Human IgM Inhibits the Formation of Titan-Like Cells in Cryptococcus neoformans.” Infect Immun 88, no. 4 (March 23, 2020). https://doi.org/10.1128/IAI.00046-20.

PMID
31988178
Full Text

Chhetri, Abhishek, Anna Loksztejn, Hai Nguyen, Kaila M. Pianalto, Mi Jung Kim, Jiyong Hong, J Andrew Alspaugh, and Kenichi Yokoyama. “Length Specificity and Polymerization Mechanism of (1,3)-β-d-Glucan Synthase in Fungal Cell Wall Biosynthesis.” Biochemistry 59, no. 5 (February 11, 2020): 682–93. https://doi.org/10.1021/acs.biochem.9b00896.

PMID
31899625
Full Text

Gusa, Asiya, Jonathan Williams, Jang-Eun Cho, Anna Floyd-Averette, Sheng Sun, Eva Mei Shouse, Joseph Heitman, Andrew Alspaugh, and Sue Jinks-Robertson. “Transposon mobilization in the human fungal pathogen Cryptococcus deneoformans is mutagenic during infection and promotes drug resistance in vitro,” January 30, 2020. https://doi.org/10.1101/2020.01.29.924845.

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