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David S. Askew, PhD

Professor

Pathology & Laboratory Medicine | College of Medicine

Education/Credentials
  • Postdoctoral Fellow: St. Jude Children's Research Hospital
  • Postdoctoral Fellow, : Frederick Cancer Research Facility
  • Doctoral Degree: University of British Columbia (Cell Biology)
  • Bachelor's Degree : University of British Columbia (Microbiology)
Contact Information
Research Interests

Aspergillus fumigatus is an environmental mold that is responsible for life-threatening pulmonary infections. The fungus is a potent opportunistic pathogen that takes advantage of weakened immune systems to establish an infection. For this reason, patients with hematologic malignancies, or those receiving immunosuppressive therapies for the treatment of organ transplantation are most at risk for developing the disease. The mission of our laboratory is two-fold: (1) to identify the fungal pathways...

Peer Reviewed Publications

Guirao-Abad, José P; Weichert, Martin; Albee, Aaron; Deck, Katie; Askew, David S 2020. A Human IRE1 Inhibitor Blocks the Unfolded Protein Response in the Pathogenic Fungus Aspergillus fumigatus and Suggests Noncanonical Functions within the Pathway. mSphere, 5 5,

Weichert, Martin; Guirao-Abad, José; Aimanianda, Vishukumar; Krishnan, Karthik; Grisham, Christina; Snyder, Patrick; Sheehan, Alex; Abbu, Ruthvik R; Liu, Hong; Filler, Scott G; Gruenstein, Eric I; Latgé, Jean-Paul; Askew, David S 2020. Functional Coupling between the Unfolded Protein Response and Endoplasmic Reticulum/Golgi Ca2+-ATPases Promotes Stress Tolerance, Cell Wall Biosynthesis, and Virulence of Aspergillus fumigatus. mBio, 11 3,

Raj, Shriya; Krishnan, Karthik; Askew, David S; Helynck, Olivier; Suzanne, Peggy; Lesnard, Aurélien; Rault, Sylvain; Zeidler, Ute; d'Enfert, Christophe; Latgé, Jean-Paul; Munier-Lehmann, Hélène; Saveanu, Cosmin 2016. The Toxicity of a Novel Antifungal Compound Is Modulated by Endoplasmic Reticulum-Associated Protein Degradation Components. Antimicrobial agents and chemotherapy, 60 3, 1438-49

Krishnan, Karthik; Ren, Zhaowei; Losada, Liliana; Nierman, William C; Lu, Long Jason; Askew, David S 2014. Polysome profiling reveals broad translatome remodeling during endoplasmic reticulum (ER) stress in the pathogenic fungus Aspergillus fumigatus. BMC genomics, 15 , 159

Jambunathan, Kalyani; Watson, Douglas S; Najvar, Laura K; Wiederhold, Nathan P; Kirkpatrick, William R; Patterson, Thomas F; Askew, David S; Kodukula, Krishna; Galande, Amit K 2013. Prolyl endopeptidase activity in bronchoalveolar lavage fluid: a novel diagnostic biomarker in a guinea pig model of invasive pulmonary aspergillosis. Medical mycology, 51 6, 592-602

Krishnan, Karthik; Feng, Xizhi; Powers-Fletcher, Margaret V; Bick, Gregory; Richie, Daryl L; Woollett, Laura A; Askew, David S 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. Eukaryotic cell, 12 4, 512-9

Powers-Fletcher, M. V.; Feng, X.; Krishnan, K.; Askew, D. S. 2013. Deletion of the sec4 Homolog srgA from Aspergillus fumigatus Is Associated with an Impaired Stress Response, Attenuated Virulence and Phenotypic Heterogeneity PLoS One, 8 6 , e66741

Powers-Fletcher, Margaret V; Feng, Xizhi; Krishnan, Karthik; Askew, David S 2013. Deletion of the sec4 homolog srgA from Aspergillus fumigatus is associated with an impaired stress response, attenuated virulence and phenotypic heterogeneity. PloS one, 8 6, e66741

Gravelat, F. N.; Askew, D. S.; Sheppard, D. C. 2012. Targeted gene deletion in Aspergillus fumigatus using the hygromycin-resistance split-marker approach Methods Mol Biol, 845 4 , 119-30

Feng, X.; Krishnan, K.; Richie, D. L.; Aimanianda, V.; Hartl, L.; Grahl, N.; Powers-Fletcher, M. V.; Zhang, M.; Fuller, K. K.; Nierman, W. C.; Lu, L. J.; Latge, J. P.; Woollett, L.; Newman, S. L.; Cramer, R. A., Jr.; Rhodes, J. C.; Askew, D. S. 2011. HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus PLoS Pathog, 7 10 , e1002330

Feng, Xizhi; Krishnan, Karthik; Richie, Daryl L; Aimanianda, Vishukumar; Hartl, Lukas; Grahl, Nora; Powers-Fletcher, Margaret V; Zhang, Minlu; Fuller, Kevin K; Nierman, William C; Lu, Long Jason; Latgé, Jean-Paul; Woollett, Laura; Newman, Simon L; Cramer, Robert A; Rhodes, Judith C; Askew, David S 2011. HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus. PLoS pathogens, 7 10, e1002330

Fuller, Kevin K; Richie, Daryl L; Feng, Xizhi; Krishnan, Karthik; Stephens, Timothy J; Wikenheiser-Brokamp, Kathryn A; Askew, David S; Rhodes, Judith C 2011. Divergent Protein Kinase A isoforms co-ordinately regulate conidial germination, carbohydrate metabolism and virulence in Aspergillus fumigatus. Molecular microbiology, 79 4, 1045-62

Powers-Fletcher, Margaret V; Jambunathan, Kalyani; Brewer, Jordan L; Krishnan, Karthik; Feng, Xizhi; Galande, Amit K; Askew, David S 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

Richie, D. L.; Feng, X.; Hartl, L.; Aimanianda, V.; Krishnan, K.; Powers-Fletcher, M. V.; Watson, D. S.; Galande, A. K.; White, S. M.; Willett, T.; Latge, J. P.; Rhodes, J. C.; Askew, D. S. 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 , 12-21

Richie, D. L.; Feng, X.; Krishnan, K.; Askew, D. S. 2011. Secretion stress and antifungal resistance: an Achilles' heel of Aspergillus fumigatus? Med Mycol, 49 Suppl 1 10 , S101-6

Richie, Daryl L; Feng, Xizhi; Hartl, Lukas; Aimanianda, Vishukumar; Krishnan, Karthik; Powers-Fletcher, Margaret V; Watson, Douglas S; Galande, Amit K; White, Stephanie M; Willett, Taryn; Latgé, Jean-Paul; Rhodes, Judith C; Askew, David S 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, 12-21

Watson, Douglas S; Feng, Xizhi; Askew, David S; Jambunathan, Kalyani; Kodukula, Krishna; Galande, Amit K 2011. Substrate specifity profiling of the Aspergillus fumigatus proteolytic secretome reveals consensus motifs with predominance of Ile/Leu and Phe/Tyr. PloS one, 6 6, e21001

Watson, Douglas S; Jambunathan, Kalyani; Askew, David S; Kodukula, Krishna; Galande, Amit K 2011. Robust substrate profiling method reveals striking differences in specificities of serum and lung fluid proteases. BioTechniques, 51 2, 95-104

Park, S. J.; Burdick, M. D.; Brix, W. K.; Stoler, M. H.; Askew, D. S.; Strieter, R. M.; Mehrad, B. 2010. Neutropenia enhances lung dendritic cell recruitment in response to Aspergillus via a cytokine-to-chemokine amplification loop J Immunol, 185 10 , 6190-7

Fuller, Kevin K; Zhao, Wei; Askew, David S; Rhodes, Judith C 2009. Deletion of the protein kinase A regulatory subunit leads to deregulation of mitochondrial activation and nuclear duplication in Aspergillus fumigatus. Eukaryotic cell, 8 3, 271-7

Richie, Daryl L; Hartl, Lukas; Aimanianda, Vishukumar; Winters, Michael S; Fuller, Kevin K; Miley, Michael D; White, Stephanie; McCarthy, Jason W; Latgé, Jean-Paul; Feldmesser, Marta; Rhodes, Judith C; Askew, David S 2009. A role for the unfolded protein response (UPR) in virulence and antifungal susceptibility in Aspergillus fumigatus. PLoS pathogens, 5 1, e1000258

Askew, D. S. 2008. Aspergillus fumigatus: virulence genes in a street-smart mold Curr Opin Microbiol, 11 4 , 331-7

Bhabhra, Ruchi; Richie, Daryl L; Kim, H Stanley; Nierman, William C; Fortwendel, Jarrod; Aris, John P; Rhodes, Judith C; Askew, David S 2008. Impaired ribosome biogenesis disrupts the integration between morphogenesis and nuclear duplication during the germination of Aspergillus fumigatus. Eukaryotic cell, 7 4, 575-83

Fortwendel, Jarrod R; Fuller, Kevin K; Stephens, Timothy J; Bacon, W Clark; Askew, David S; Rhodes, Judith C 2008. Aspergillus fumigatus RasA regulates asexual development and cell wall integrity. Eukaryotic cell, 7 9, 1530-9

Richie, D. L.; Askew, D. S. 2008. Autophagy in the filamentous fungus Aspergillus fumigatus Methods Enzymol, 451 10 , 241-50

Richie, Daryl L; Fuller, Kevin K; Fortwendel, Jarrod; Miley, Michael D; McCarthy, Jason W; Feldmesser, Marta; Rhodes, Judith C; Askew, David S 2007. Unexpected link between metal ion deficiency and autophagy in Aspergillus fumigatus. Eukaryotic cell, 6 12, 2437-47

Richie, Daryl L; Miley, Michael D; Bhabhra, Ruchi; Robson, Geoffrey D; Rhodes, Judith C; Askew, David S 2007. The Aspergillus fumigatus metacaspases CasA and CasB facilitate growth under conditions of endoplasmic reticulum stress. Molecular microbiology, 63 2, 591-604

Bhabhra, Ruchi; Zhao, Wei; Rhodes, Judith C; Askew, David S 2006. Nucleolar localization of Aspergillus fumigatus CgrA is temperature-dependent. Fungal genetics and biology : FG & B, 43 1, 1-7

Zhao, Wei; Panepinto, John C; Fortwendel, Jarrod R; Fox, Lauren; Oliver, Brian G; Askew, David S; Rhodes, Judith C 2006. Deletion of the regulatory subunit of protein kinase A in Aspergillus fumigatus alters morphology, sensitivity to oxidative damage, and virulence. Infection and immunity, 74 8, 4865-74

Bhabhra, R.; Askew, D. S. 2005. Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus Med Mycol, 43 Suppl 1 1 , S87-93

Fortwendel, Jarrod R; Zhao, Wei; Bhabhra, Ruchi; Park, Steven; Perlin, David S; Askew, David S; Rhodes, Judith C 2005. A fungus-specific ras homolog contributes to the hyphal growth and virulence of Aspergillus fumigatus. Eukaryotic cell, 4 12, 1982-9

Vogt, Keith; Bhabhra, Ruchi; Rhodes, Judith C; Askew, David S 2005. Doxycycline-regulated gene expression in the opportunistic fungal pathogen Aspergillus fumigatus. BMC microbiology, 5 , 1

Bhabhra, Ruchi; Miley, Michael D; Mylonakis, Eleftherios; Boettner, Doug; Fortwendel, Jarrod; Panepinto, John C; Postow, Michael; Rhodes, Judith C; Askew, David S 2004. Disruption of the Aspergillus fumigatus gene encoding nucleolar protein CgrA impairs thermotolerant growth and reduces virulence. Infection and immunity, 72 8, 4731-40

Fortwendel, Jarrod R; Panepinto, John C; Seitz, Amy E; Askew, David S; Rhodes, Judith C 2004. Aspergillus fumigatus rasA and rasB regulate the timing and morphology of asexual development. Fungal genetics and biology : FG & B, 41 2, 129-39

Panepinto, John C; Oliver, Brian G; Fortwendel, Jarrod R; Smith, Darcey L H; Askew, David S; Rhodes, Judith C 2003. Deletion of the Aspergillus fumigatus gene encoding the Ras-related protein RhbA reduces virulence in a model of Invasive pulmonary aspergillosis. Infection and immunity, 71 5, 2819-26

Moy, Terence I; Boettner, Douglas; Rhodes, Judith C; Silver, Pamela A; Askew, David S 2002. Identification of a role for Saccharomyces cerevisiae Cgr1p in pre-rRNA processing and 60S ribosome subunit synthesis. Microbiology (Reading, England), 148 Pt 4, 1081-90

Oliver, Brian G; Panepinto, John C; Askew, David S; Rhodes, Judith C 2002. cAMP alteration of growth rate of Aspergillus fumigatus and Aspergillus niger is carbon-source dependent. Microbiology (Reading, England), 148 Pt 8, 2627-33

Oliver, Brian G; Panepinto, John C; Fortwendel, Jarrod R; Smith, Darcey L; Askew, David S; Rhodes, Judith C 2002. Cloning and expression of pkaC and pkaR, the genes encoding the cAMP-dependent protein kinase of Aspergillus fumigatus. Mycopathologia, 154 2, 85-91

Panepinto, John C; Oliver, Brian G; Amlung, Thomas W; Askew, David S; Rhodes, Judith C 2002. Expression of the Aspergillus fumigatus rheb homologue, rhbA, is induced by nitrogen starvation. Fungal genetics and biology : FG & B, 36 3, 207-14

Boettner, D.; Huebner, N.; Rhodes, J. C.; Askew, D. S. 2001. Molecular cloning of Aspergillus fumigatus CgrA, the ortholog of a conserved fungal nucleolar protein Med Mycol, 39 6 , 517-21

Rhodes, J. C.; Oliver, B. G.; Askew, D. S.; Amlung, T. W. 2001. Identification of genes of Aspergillus fumigatus up-regulated during growth on endothelial cells Med Mycol, 39 3 , 253-60

Sun, J; Boettner, D; Huebner, N; Xu, F; Rhodes, J C; Askew, D S 2001. Molecular cloning of cgrA, the gene encoding the Aspergillus nidulans ortholog of Saccharomyces cerevisiae CGR1. Current microbiology, 42 6, 403-7

Sun, J; McFarland, M; Boettner, D; Panepinto, J; Rhodes, J C; Askew, D S 2001. Cgr1p, a novel nucleolar protein encoded by Saccharomyces cerevisiae orf YGL0292w. Current microbiology, 42 1, 65-9

Sun, J.; Rhodes, J. C.; Askew, D. S. 1998. Sequencing of a gene encoding a member of the mitochondrial carrier family of transport proteins from Aspergillus nidulans DNA Seq, 9 1 , 1-8

Li, J; Witte, D P; Van Dyke, T; Askew, D S 1997. Expression of the putative proto-oncogene His-1 in normal and neoplastic tissues. The American journal of pathology, 150 4, 1297-305

Askew, D S; Li, J; Ihle, J N 1994. Retroviral insertions in the murine His-1 locus activate the expression of a novel RNA that lacks an extensive open reading frame. Molecular and cellular biology, 14 3, 1743-51

Abstract Publications

Guirao-Abad, JP, Weichert M, Albee A, Deck K, Askew DS 2020. A Human IRE1 Inhibitor Blocks the Unfolded Protein Response in the Pathogenic Fungus Aspergillus fumigatus and Suggests Noncanonical Functions within the Pathway mSphere, 5(5): 2020 Oct 21, e00879-20