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

Paes, Hugo Costa, Lorena da Silveira Derengowski, Luisa Defranco Ferreira Peconick, Patrícia Albuquerque, Georgios Joannis Pappas, André Moraes Nicola, Fabiana Brandão Alves Silva, et al. “A Wor1-Like Transcription Factor Is Essential for Virulence of Cryptococcus neoformans..” Front Cell Infect Microbiol 8 (2018). https://doi.org/10.3389/fcimb.2018.00369.

PMID
30483479
Full Text

Hemmersbach-Miller, Marion, Emily S. Bailey, Matthew Kappus, Vinod K. Prasad, Gregory C. Gray, and J Andrew Alspaugh. “Disseminated Adenovirus Infection After Combined Liver-Kidney Transplantation..” Front Cell Infect Microbiol 8 (2018). https://doi.org/10.3389/fcimb.2018.00408.

PMID
30524972
Full Text

Ost, Kyla S., Shannon K. Esher, Chrissy M. Leopold Wager, Louise Walker, Jeanette Wagener, Carol Munro, Floyd L. Wormley, and J Andrew Alspaugh. “Rim Pathway-Mediated Alterations in the Fungal Cell Wall Influence Immune Recognition and Inflammation..” Mbio 8, no. 1 (January 31, 2017). https://doi.org/10.1128/mBio.02290-16.

PMID
28143983
Full Text

Gontijo, Fabiano de Assis, Amanda Teixeira de Melo, Renata C. Pascon, Larissa Fernandes, Hugo Costa Paes, J Andrew Alspaugh, and Marcelo A. Vallim. “The role of Aspartyl aminopeptidase (Ape4) in Cryptococcus neoformans virulence and authophagy..” Plos One 12, no. 5 (2017). https://doi.org/10.1371/journal.pone.0177461.

PMID
28542452
Full Text

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.

PMID
27303728
Full Text

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.

PMID
26112692
Full Text

Pages