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

Brandão, F, Esher, SK, Ost, KS, Pianalto, K, Nichols, CB, Fernandes, L, Bocca, AL, Poças-Fonseca, MJ, and Alspaugh, JA. "HDAC genes play distinct and redundant roles in Cryptococcus neoformans virulence." Scientific reports 8, no. 1 (March 26, 2018): 5209-.

PMID
29581526
Full Text

Xu, L, Li, Y, Biggins, JB, Bowman, BR, Verdine, GL, Gloer, JB, Alspaugh, JA, and Bills, GF. "Identification of cyclosporin C from Amphichorda felina using a Cryptococcus neoformans differential temperature sensitivity assay." Applied microbiology and biotechnology 102, no. 5 (March 2018): 2337-2350.

PMID
29396588
Full Text

Alspaugh, JA. "Targeting protein localization for anti-infective therapy." Virulence 8, no. 7 (October 2017): 1105-1107.

PMID
28658594
Full Text

Ost, KS, Esher, SK, Leopold Wager, CM, Walker, L, Wagener, J, Munro, C, Wormley, FL, and Alspaugh, JA. "Rim Pathway-Mediated Alterations in the Fungal Cell Wall Influence Immune Recognition and Inflammation." mBio 8, no. 1 (January 31, 2017).

PMID
28143983
Full Text

Gontijo, FDA, de Melo, AT, Pascon, RC, Fernandes, L, Paes, HC, Alspaugh, JA, and Vallim, MA. "The role of Aspartyl aminopeptidase (Ape4) in Cryptococcus neoformans virulence and authophagy." PloS one 12, no. 5 (January 2017): e0177461-.

PMID
28542452
Full Text

Alspaugh, JA. "Discovery of Ibomycin, a Potent Antifungal Weapon." Cell chemical biology 23, no. 11 (November 2016): 1321-1322.

PMID
27863218
Full Text

Pianalto, KM, and Alspaugh, JA. "New Horizons in Antifungal Therapy." Journal of fungi (Basel, Switzerland) 2, no. 4 (October 2, 2016). (Review)

PMID
29376943
Full Text

Esher, SK, Ost, KS, Kozubowski, L, Yang, D-H, Kim, MS, Bahn, Y-S, Alspaugh, JA, and Nichols, CB. "Relative Contributions of Prenylation and Postprenylation Processing in Cryptococcus neoformans Pathogenesis." mSphere 1, no. 2 (March 30, 2016).

PMID
27303728
Full Text

Alspaugh, JA. "Unveiling Protein Kinase A Targets in Cryptococcus neoformans Capsule Formation." mBio 7, no. 1 (January 2016): e00021-e00016.

PMID
26861014
Full Text

Esher, SK, Granek, JA, and Alspaugh, JA. "Rapid mapping of insertional mutations to probe cell wall regulation in Cryptococcus neoformans." Fungal genetics and biology : FG & B 82 (September 2015): 9-21.

PMID
26112692
Full Text

Pages