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Andrew Alspaugh

Professor in Medicine, and Associate Professor in MGM
Molecular Genetics and Microbiology
(919) 684-0045
Research Interest: 
Microbiology and virology
Signal transduction
Research Summary: 
Intracellular signaling pathways that are activated in pathogenic microorganisms and allow survival in the host.
Research Description: 

In order to cause human infections, microorganisms must be able to adapt to the hostile environment of the infected host. For example, one of the fungi that we study in the laboratory, Cryptococcus neoformans, creates a large surface capsule to avoid the host immune system. Capsule is highly expressed in the setting of infection, and minimally expressed when the fungus grows in the test tube. We are interested in determining how infectious microorganisms sense the host and respond with these types of protective cellular responses. In this way, we hope to identify new targets for treating infectious diseases.

Our laboratory primarily uses the tools of fungal genetics to study the pathogenic process. Fungal pathogens have become increasingly important in immunocompromised patients, especially those with HIV infection or organ transplantation. By defining and manipulating gene expression patterns in these microorganisms, we are able to assign function to specific gene products. By looking at global genome expression patterns, we are finding new genes and gene families that are important for microbial pathogenesis.

Specific projects:

1) Identifying downstream targets of the cAMP/PKA pathway regulating C. neoformans capsule production
2) Defining mediators of fungal cell polarity and morphogenesis that are required for pathogenesis
3) Testing for chemical inhibitors of Ras protein function as potential novel antifungal agents

Interaction of Cryptococcus neoformans Rim101 and protein kinase A regulates capsule.
O'Meara TR, Norton D, Price MS, Hay C, Clements MF, Nichols CB, Alspaugh JA.
PLoS Pathog. 2010. 6:e1000776.

Structures of Cryptococcus neoformans protein farnesyltransferase reveal strategies for developing inhibitors that target fungal pathogens.
Hast MA, Nichols CB, Armstrong SM, Kelly SM, Hellinga HW, Alspaugh JA, Beese LS.
J Biol Chem. 2011. 286:35149-62.

Cryptococcus neoformans Rim101 is associated with cell wall remodeling and evasion of the host immune responses.
O'Meara TR, Holmer SM, Selvig K, Dietrich F, Alspaugh JA.
MBio. 2013. 4: .

Ras1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and pathogenesis in the human fungal pathogen Cryptococcus neoformans.
Ballou ER, Kozubowski L, Nichols CB, Alspaugh JA.
PLoS Genet. 2013. 9:e1003687.

The Cryptococcus neoformans Rim101 transcription factor directly regulates genes required for adaptation to the host.
O'Meara TR, Xu W, Selvig KM, O'Meara MJ, Mitchell AP, Alspaugh JA.
Mol Cell Biol. 2014. 34:673-84.