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


Esher, Shannon K., Kyla S. Ost, Lukasz Kozubowski, Dong-Hoon Yang, Min Su Kim, Yong-Sun Bahn, J Andrew Alspaugh, and Connie B. Nichols. “Relative Contributions of Prenylation and Postprenylation Processing in Cryptococcus neoformans Pathogenesis.” Msphere 1, no. 2 (March 2016). https://doi.org/10.1128/mSphere.00084-15.

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Esher, Shannon K., Joshua A. Granek, and J Andrew Alspaugh. “Rapid mapping of insertional mutations to probe cell wall regulation in Cryptococcus neoformans.” Fungal Genet Biol 82 (September 2015): 9–21. https://doi.org/10.1016/j.fgb.2015.06.003.

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Nichols, Connie B., Kyla S. Ost, Dayton P. Grogan, Kaila Pianalto, Shirin Hasan, and J Andrew Alspaugh. “Impact of Protein Palmitoylation on the Virulence Potential of Cryptococcus neoformans.” Eukaryot Cell 14, no. 7 (July 2015): 626–35. https://doi.org/10.1128/EC.00010-15.

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Ost, Kyla S., Teresa R. O’Meara, Naureen Huda, Shannon K. Esher, and J Andrew Alspaugh. “The Cryptococcus neoformans alkaline response pathway: identification of a novel rim pathway activator.” Plos Genet 11, no. 4 (April 2015): e1005159. https://doi.org/10.1371/journal.pgen.1005159.

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Gontijo, Fabiano Assis de, Renata C. Pascon, Larissa Fernandes, Joel Machado, J Andrew Alspaugh, and Marcelo A. Vallim. “The role of the de novo pyrimidine biosynthetic pathway in Cryptococcus neoformans high temperature growth and virulence.” Fungal Genet Biol 70 (September 2014): 12–23. https://doi.org/10.1016/j.fgb.2014.06.003.

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Oliveira, F. F. M., H. C. P. Costa Paes, L. D. F. Peconick, P. Albuquerque, A. M. Nicola, M. H. Melo, F. L. Fonseca, et al. “Erg6 is a potential drug target in Cryptococcus neoformans.” Mycoses 57 (May 1, 2014): 46–47.