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

Brown, HE, Ost, KS, Esher, SK, Pianalto, KM, Saelens, JW, Guan, Z, and Alspaugh, JA. "Identifying a Novel Connection Between the Fungal Plasma Membrane and pH-Sensing." Molecular Microbiology (June 8, 2018).

PMID
29885030
Full Text

Esher, SK, Ost, KS, Kohlbrenner, MA, Pianalto, KM, Telzrow, CL, Campuzano, A, Nichols, CB, Munro, C, Wormley, FL, and Alspaugh, JA. "Defects in intracellular trafficking of fungal cell wall synthases lead to aberrant host immune recognition." Plos Pathogens 14, no. 6 (June 4, 2018): e1007126-null.

PMID
29864141
Full Text

Pianalto, KM, Ost, KS, Brown, HE, and Alspaugh, JA. "Characterization of additional components of the environmental pH-sensing complex in the pathogenic fungus Cryptococcus neoformans." The Journal of Biological Chemistry 293, no. 26 (June 2018): 9995-10008.

PMID
29769315
Full Text

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-null.

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

Esher, SK, Zaragoza, O, and Alspaugh, JA. "Cryptococcal pathogenic mechanisms: a dangerous trip from the environment to the brain." Memorias Do Instituto Oswaldo Cruz 113, no. 7 (January 2018): e180057-null. (Review)

PMID
29668825
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

Pages