Department of Pathology & Laboratory Medicine
David S. Askew, Ph.D.
University of British Columbia, Canada, Ph.D., 1986Aspergillus fumigatus is an environmental mould that propagates itself by the release into the air of high concentrations of conidia (spores), which are unavoidably inhaled. Patients who are immunosuppressed, such as cancer or transplant patients, are at increased risk for infection with these conidia, and the prognosis for invasive infections is very poor. Our lab is interested in how A. fumigatus balances its biosynthetic and degradative needs to optimize growth in the host, with the goal of developing new antifungal therapies that tip the balance in favor of degradation and fungal death. As a major component of the biomass in a self-heating compost pile, A. fumigatus has evolved thermotolerant biosynthetic activities that support rapid growth at 37oC. We have shown that one of these activities involves CgrA, a ribosome biogenesis protein. The objective of the lab is to further understand how CgrA promotes thermotolerance, with the long-term goal of identifying new strategies to disrupt the growth of the organism at 37oC.
We are also interested in mechanisms that regulate fungal programmed cell death (PCD). PCD has been divided into two major categories based on the effectors involved: caspase-dependent PCD (type I) and autophagy-dependent PCD (type II). Comparisons between mammalian and fungal genomes suggest that both of these pathways exist in lower eukaryotes. However, little is understood about their nature and function in filamentous fungi. The goal of the lab is to characterize the molecules involved in these pathways, and to understand their contribution to the growth and virulence of A. fumigatus.
Recent Publications
- Richie, D.L., Fuller, K.K., Fortwendel, J., Miley, M.D., McCarthy, J.W.,
Feldmesser, M., Rhodes, J.C., Askew, D.S. (2007). An unexpected link between
metal ion deficiency and autophagy in Aspergillus fumigatus. Euk. Cell
(in press).
- Richie, D.L., Miley, M.D., Bhabhra, R., Robson, G.D., Rhodes, J.C., Askew,
D.S. (2007). The Aspergillus fumigatus metacaspases CasA and CasB facilitate
growth under conditions of endoplasmic reticulum stress. Molec. Microbiol.
63(2):591-604.
- Bhabhra, R., Zhao, W., Rhodes, J.C., Askew, D.S. (2006). Nucleolar localization
of Aspergillus fumigatus CgrA is temperature-dependent. Fung. Genet. Biol. 43:1-7.
- Vogt, K., Bhabhra, R., Rhodes, JC., Askew, D.S. (2005) Doxycycline-regulated
gene expression in the opportunistic fungal pathogen Aspergillus fumigatus.
BMC Microbiol. 5:1.
- Bhabhra, R., Miley, M.D., Mylonakis, E., Boettner, D., Fortwendel, J., Panepinto, J.C., Postow, M., Rhodes, J.C., Askew, D.S. (2004). Disruption of the Aspergillus fumigatus gene encoding nucleolar protein CgrA impairs thermotolerant growth and reduces virulence. Infect. Immun. 72(8): 4731-4740.
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