David S Askew , PhD
Professor
Office 1256A Medical Sciences Building
231 Albert Sabin Way
Cincinnati, Ohio 45267-0529
Phone (513) 558-2395
Fax (513) 558-2289
Email david.askew@uc.edu
Professional Summary
Research:
I am a Professor in the Department of Pathology and Laboratory Medicine. My research interests are in the general area of pathogenic mycology, focusing on mechanisms of virulence in the human mold pathogen Aspergillus fumigatus.
Teaching (course directing):
- Medical Histology (undergraduate medical sciences/graduate)
- Medical Microbiology (undergraduate medical sciences/graduate)
- Health & Community: Service Learning Capstone (undergraduate medical sciences).
- Health & Community: Service Learning Rotation (undergraduate medical sciences).
- Biology of Cancer (graduate)
- Microbiology & Immunology (graduate)
- Pathobiology & Molecular Medicine Journal club (graduate)
- Fundamentals of Molecular Medicine Block (medical school)
- Fundamentals of Cellular Medicine Block (medical school)
- Musculoskeletal-Integumentary Block (medical school)
Education
Bachelor's Degree : University of British Columbia Vancouver, Canada, 1981 (Microbiology)
Doctoral Degree: University of British Columbia Vancouver, Canada, 1986 (Cell Biology)
Postdoctoral Fellow, : Frederick Cancer Research Facility Frederick, MD, 1988
Postdoctoral Fellow: St. Jude Children's Research Hospital 1992
Research and Practice 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 that allow A. fumigatus to thrive in the host environment and (2) to understand how the immune response protects against the infection. Our long-term goal is to provide a rational basis for the design of novel therapeutic strategies that can impair the growth of the of fungus during infection, thereby improving patient outcome.
Positions and Work Experience
2010 -To Present Professor, Dept. of Pathology and Laboratory Medicine, University of Cincinnati
2002 -2010 Associate Professor, Dept. of Pathology & Laboratory Medicine, University of Cincinnati
1996 -2002 Assistant Professor, tenure track, Dept. of Pathology & Laboratory Medicine, University of Cincinnati
1993 -1996 Assistant Professor, research track, Dept. of Pathology & Laboratory Medicine, University of Cincinnati
Research Support
Grant: #R21-AI-061495 Investigators:Askew, David 04-01-2005 -03-31-2008 National Institute of Allergy and Infectious Diseases Caspase Activity and Virulence of Aspergillis Fumigatus Role:PI Closed 001730-001 Level:Federal
Grant: #ASKEW07G0 Investigators:Askew, David 04-01-2007 -03-31-2009 Cystic Fibrosis Foundation ER Stress as a Therapeutic Target for Aspergillus Fumigatus Role:PI Closed 002550-001 Level:Private Non-Profit
Grant: #5-R01-AI-048746-03-A0-S0-E0 Investigators:Askew, David 02-15-2002 -01-31-2005 National Institute of Allergy and Infectious Diseases The Nucleolus as a Therapeutic Target for A. Fumigatus Role:PI Closed 003968-001 Level:Federal
Grant: #5-R03-AI-053184-02-A0-S0-E0 Investigators:Askew, David 09-15-2002 -09-14-2005 National Institute of Allergy and Infectious Diseases A tetR/teto-regulated Promoter System for A. Fumigatus Role:PI Closed 004130-001 Level:Federal
Grant: #5-R29-CA-61909-05-A0-S0-E0 Investigators:Askew, David 01-01-1994 -12-31-1999 National Cancer Institute Analysis of the HIS-1 Gene and Its Role in Leukemogenesis Role:PI Closed 004198-001 Level:Federal
Grant: #R01 AI072297 Investigators:Askew, David; Rhodes, Judith 12-01-2007 -11-30-2012 National Institute of Allergy and Infectious Diseases ER Stress and Virulence of Aspergillus Fumigatus Role:PI Active 005311-001 Level:Federal
Grant: #R21 AI075237 Investigators:Askew, David 02-01-2008 -01-31-2011 National Institute of Allergy and Infectious Diseases Translation State Array Analysis in Aspergillus Fumigatus Role:PI Closed 005442-001 Level:Federal
Grant: #76-000024 / 1 R21 AI085402-01 Investigators:Askew, David 03-04-2010 -12-31-2011 National Institute of Allergy and Infectious Diseases Detection of Fungus-Derived Proteolytic Activity During Invasive Aspergillosis Role:PI Active 006803-001 Level:Federal
Grant: #CHMC 106210 / F30HL097609 Investigators:Askew, David; Simpson, David Scott 08-11-2009 -04-10-2011 National Heart, Lung and Blood Institute Role of Rb/p16 pathway in Pulmonary Progenitor Cell Regulation Role:PI $50,986.00 Closed Level:Federal
Grant: #R56 AI107036 Investigators:Askew, David 08-15-2013 -07-31-2014 National Institute of Allergy and Infectious Diseases High-density lipoprotein and A. fumigatus pathogenesis Role:PI $358,728.00 Awarded Level:Federal
Grant: #1R21 AI111062 Investigators:Askew, David 02-01-2014 -01-31-2016 National Institute of Allergy and Infectious Diseases Translational repression & Aspergillus fumigatus virulence Role:PI $200,813.00 Awarded Level:Federal
Grant: #R01AI159078 Investigators:Askew, David; Kanisicak, Onur 09-21-2021 -08-31-2026 National Institute of Allergy and Infectious Diseases Aspergillus fumigatus infection and fibrosis Role:PI 405000.00 Awarded Level:Federal
Grant: #R01AI123158 Investigators:Askew, David; Conforti, Laura; Krishnan, Karthik 09-27-2016 -08-31-2021 National Institute of Allergy and Infectious Diseases ER stress and calcium in host adaptation of A. fumigatus Role:PI $387,568.00 Active Level:Federal
Grant: #ASKEW16P0 Investigators:Askew, David; Hassett, Daniel 09-01-2016 -08-31-2017 Cystic Fibrosis Foundation Neutrophils and ER stress in host adaptation by Aspergillus fumigatus Role:PI $125,000.00 Active Level:Private Non-Profit
Publications
Published Abstracts
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 .[Abstract]mSphere, 5(5): (2020 Oct 21 ) ,e00879-20
Peer Reviewed Publications
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
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 More Information
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
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 More Information
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
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 More Information
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 More Information
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 More Information
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
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 More Information
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 More Information
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 More Information
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 More Information
Askew, D. S. (2008. ) Aspergillus fumigatus: virulence genes in a street-smart mold .Curr Opin Microbiol, , 11 (4 ) ,331-7
Richie, D. L.; Askew, D. S. (2008. ) Autophagy in the filamentous fungus Aspergillus fumigatus .Methods Enzymol, , 451 (10 ) ,241-50
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 More Information
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
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 More Information
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 More Information
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
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 More Information
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, 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
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
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
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 More Information
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 More Information
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 More Information
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 More Information
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 More Information
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 More Information
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 More Information
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 ) , More Information
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
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 ) , More Information
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 More Information
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
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
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 More Information
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 More Information
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
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 More Information
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
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
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
Keywords
Nucleolus,Aspergillus Fumigatus,Fungal Pathogenesis,Virulence Mechanisms,Antifungal Targets
Contact Information
Academic - Office 1256A Medical Sciences Building
231 Albert Sabin Way
Cincinnati
Ohio, 45267-0529
Phone: (513) 558-2395
Fax: (513) 558-2289
david.askew@uc.edu