David Askew, PhD
|Pathology & Lab Med|
P. O. Box 670529
Cincinnati OH 45267
Aspergillus 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. Despite some advances in therapy, invasive aspergillosis continues to have a poor outcome, emphasizing the need for more information on fungal pathways that are essential to the growth of the organism in vivo. The ability of A. fumigatus to thrive in the host environment requires the secretion of abundant degradative enzymes. This exerts stress on the endoplasmic reticulum (ER) of the fungus, which is countered by the activation of a stress response pathway termed the unfolded protein response (UPR).
Our lab is currently interested in understanding how A. fumigatus harnesses the UPR and associated pathways to meet the demands of a high capacity secretory system, with the long term goal of developing new antifungal therapies that can interrupt ER homeostasis.
Krishnan K, Askew DS. (2014). Endoplasmic reticulum stress and fungal pathogenesis. Fung. Biol. Rev. 28:29-35.
Krishnan K, Askew DS. (2014). The fungal UPR: A regulatory hub for virulence traits in the mold pathogen Aspergillus fumigatus. Virulence. 15;5(2):334-340. PMID: 24189125.
Krishnan K, Ren Z, Losada L, Nierman WC, Lu LJ, Askew DS. (2014). Polysome profiling reveals broad translatome remodeling during endoplasmic reticulum (ER) stress in the pathogenic fungus Aspergillus fumigatus. BMC Genomics. Feb 25;15(1):159. PMID: 24568630.
Krishnan K, Feng X, Powers-Fletcher MV, Bick G, Richie DL, Woollett LA, Askew DS. (2013). Effects of a defective endoplasmic reticulum-associated degradation pathway on the stress response, virulence, and antifungal drug susceptibility of the mold pathogen Aspergillus fumigatus. Eukaryot Cell. Apr;12(4):512-9. PMID: 23355008.
Powers-Fletcher MV, Jambunathan K, Brewer JL, Krishnan K, Feng X, Galande AK and Askew DS. (2011). Impact of the lectin chaperone calnexin on the stress response, virulence and proteolytic secretome of the fungal pathogen Aspergillus fumigatus. PLoS ONE 6(12): e28865.
Feng X, Krishnan K, Richie DL, Aimanianda V, Hartl L, Grahl N, Powers-Fletcher MV, Zhang M, Fuller KK, Nierman WC, Lu LL, Latge JP, Woollett L, Newman SL, Cramer RA, Rhodes JC, Askew DS. (2011). HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus. PLoS Pathog. Oct;7(10):e1002330. Epub 2011 Oct 20. PMID: 2202866.
Richie DL, Feng X, Hartl L, Aimanianda V, Krishnan K, Powers-Fletcher MV, Watson DS, Galande AK, White SM, Willett T, Latge J-P, Rhodes JC and Askew DS. (2011) The virulence of the opportunistic fungal pathogen Aspergillus fumigatus requires cooperation between the endoplasmic reticulum-associated degradation pathway (ERAD) and the unfolded protein response (UPR). Virulence 2(1): 1-10. PMID: 21217201.
Richie DL, Hartl L, Aimanianda V, Winters M, Fuller KK, Miley MD, White S, McCarthy JW, Latgé J-P, Feldmesser M, Rhodes JC and Askew DS (2009). A role for the unfolded protein response (UPR) in virulence and antifungal susceptibility in Aspergillus fumigatus. PLoS Pathogens Jan 5(1). PMID: 19132084.