David Askew

David S Askew

Professor

Medical Sciences Building

1256A

COM Pathology Research - 0529

Office 1256A Medical Sciences Building
231 Albert Sabin Way
Cincinnati, Ohio 45267-0529

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).
Teaching (lectures in team-taught courses):
  • 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

PhD, University of British Columbia Vancouver, Canada, 1986 (Cell Biology)

B.Sc., University of British Columbia Vancouver, Canada, 1981 (Microbiology)

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 and Practice Interests

Aspergillus fumigatus is an environmental fungus that causes life-threatening pulmonary infections that have a very high rate of mortality.  The organism is a potent opportunistic pathogen that takes advantage of a weakened immune system to establish an infection.  For this reason, patients receiving immunosuppressive therapies for the treatment of cancer or organ transplantation are most at risk for developing this disease. As a microbiology laboratory, our mission is to understand how A. fumigatus survives the stress of the host environment so that novel therapeutic strategies can be developed to interrupt these pathways and improve patient outcome.

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: #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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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, 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

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

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

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; 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

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

Post Graduate Training and Education

1986-1988 Postdoctoral Fellow, NCI-Frederick Cancer Research Facility, ,

1989-1992 Postdoctoral Fellow, St. Jude Children's Research Hospital, ,

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