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

Pianalto, Kaila M., R Blake Billmyre, Calla L. Telzrow, and J Andrew Alspaugh. “Roles for Stress Response and Cell Wall Biosynthesis Pathways in Caspofungin Tolerance in Cryptococcus neoformans..” Genetics 213, no. 1 (September 2019): 213–27. https://doi.org/10.1534/genetics.119.302290.

PMID
31266771
Full Text

Chen, Sharon F., Jennifer Deitz, Jason N. Batten, Jennifer DeCoste-Lopez, Maya Adam, J Andrew Alspaugh, Manuel R. Amieva, et al. “A Multi-Institution Collaboration to Define Core Content and Design Flexible Curricular Components for a Foundational Medical School Course: Implications for National Curriculum Reform..” Acad Med 94, no. 6 (June 2019): 819–25. https://doi.org/10.1097/ACM.0000000000002663.

PMID
30801270
Full Text

Dischler, Nicole M., Lijian Xu, Yan Li, Connie B. Nichols, J Andrew Alspaugh, Gerald F. Bills, and James B. Gloer. “Wortmannin and Wortmannine Analogues from an Undescribed Niesslia sp..” J Nat Prod 82, no. 3 (March 22, 2019): 532–38. https://doi.org/10.1021/acs.jnatprod.8b00923.

PMID
30844268
Full Text

Brown, Hannah E., Kyla S. Ost, Shannon K. Esher, Kaila M. Pianalto, Joseph W. Saelens, Ziqiang Guan, and J. Andrew Alspaugh. “Identifying a novel connection between the fungal plasma membrane and pH-sensing..” Mol Microbiol 109, no. 4 (August 2018): 474–93. https://doi.org/10.1111/mmi.13998.

PMID
29885030
Full Text

Pianalto, Kaila M., Kyla S. Ost, Hannah E. Brown, and J Andrew Alspaugh. “Characterization of additional components of the environmental pH-sensing complex in the pathogenic fungus Cryptococcus neoformans..” J Biol Chem 293, no. 26 (June 29, 2018): 9995–10008. https://doi.org/10.1074/jbc.RA118.002741.

PMID
29769315
Full Text

Esher, Shannon K., Kyla S. Ost, Maria A. Kohlbrenner, Kaila M. Pianalto, Calla L. Telzrow, Althea Campuzano, Connie B. Nichols, Carol Munro, Floyd L. Wormley, and J Andrew Alspaugh. “Defects in intracellular trafficking of fungal cell wall synthases lead to aberrant host immune recognition..” Plos Pathog 14, no. 6 (June 2018). https://doi.org/10.1371/journal.ppat.1007126.

PMID
29864141
Full Text

Brandão, Fabiana, Shannon K. Esher, Kyla S. Ost, Kaila Pianalto, Connie B. Nichols, Larissa Fernandes, Anamélia L. Bocca, Marcio José Poças-Fonseca, and J Andrew Alspaugh. “HDAC genes play distinct and redundant roles in Cryptococcus neoformans virulence..” Sci Rep 8, no. 1 (March 26, 2018). https://doi.org/10.1038/s41598-018-21965-y.

PMID
29581526
Full Text

Xu, Lijian, Yan Li, John B. Biggins, Brian R. Bowman, Gregory L. Verdine, James B. Gloer, J Andrew Alspaugh, and Gerald F. Bills. “Identification of cyclosporin C from Amphichorda felina using a Cryptococcus neoformans differential temperature sensitivity assay..” Appl Microbiol Biotechnol 102, no. 5 (March 2018): 2337–50. https://doi.org/10.1007/s00253-018-8792-0.

PMID
29396588
Full Text

Esher, Shannon K., Oscar Zaragoza, and James Andrew Alspaugh. “Cryptococcal pathogenic mechanisms: a dangerous trip from the environment to the brain..” Mem Inst Oswaldo Cruz 113, no. 7 (2018). https://doi.org/10.1590/0074-02760180057.

PMID
29668825
Full Text

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

Pages