Ashley L. Steed, M.D., Ph.D.

Assistant Professor
Pediatrics
Critical Care Medicine

Molecular Microbiology and Microbial Pathogenesis Program
Immunology Program

  • steeda@wustl.edu

  • Investigate the genetic and environmental factors that underlie the mechanistic basis for the heterogeneity in outcomes in response to infection

Research Abstract:

My research aims to investigate if the host recognition of SARS-CoV-2 triggers damaging immune responses that potentiate inflammation and drive the pathogenesis of COVID-19 critical illness. At present, it is not known how this virus activates the human immune response. Furthermore, the role of key immune signaling pathways triggered by SARS-CoV-2 infection with respect to disease outcome remain to be elucidated. As such, there is an emergent need to investigate the mechanisms underlying disease pathogenesis in order to rationally design and target appropriate therapeutic strategies. My research aims to address this critical need by (A) testing the hypothesis that cell type specific activation of peripheral immune cells predicts the development of COVID-19 critical illness, (B) determining if recognition of key structural viral proteins illicit damaging immune responses, and (C) elucidating if exaggerated inflammatory signaling in monocytes further potentiates SARS-CoV-2 pathogenesis. Achieving these goals thereby requires an assessment of (1) the immune cell specific response during mild and severe COVID-19, (2) inflammatory signaling activation by SARS-CoV-2 structural proteins, and (3) the importance of key inflammatory pathways in monocytes for disease progression. Once the host immunological response to this novel virus is more fully appreciated, our research then aims to determine both genetic and environmental modifiers (including the
microbiota) of the implicated pathways and their impact on disease pathogenesis. This knowledge is essential to overcome the current devastating pandemic and is particularly underscored by the certainty of SARS-CoV-2 persistence in the human population.

Selected Publications:

Ashley L. Steed, George P. Christophi, Gerard E. Kaiko, Lulu Sun, Victoria M. Goodwin, Umang Jain, Ekaterina Esaulova, Maxim N. Artyomov, David J. Morales, Michael J. Holtzman, Adrianus C.M. Boon, Deborah J. Lenschow, Thaddeus S. Stappenbeck. The Microbial Metabolite Desaminotyrosine Protects from Influenza through Type I Interferon Science. 2017;357(6350):498-502. PMID:28774928

Steed AL, Stappenbeck TS. Role of viruses and bacteria-virus interactions in autoimmunity. Curr Opin Immunol. 2014;31:102-7. PMCID:PMC4254666 PMID:25459001

Goodwin MM, Canny S, Steed A, Virgin HW. Murine gammaherpesvirus 68 has evolved gamma interferon and stat1-repressible promoters for the lytic switch gene 50. J Virol. 2010;84(7):3711-7. PMCID:PMC2838114 PMID:20071569

Steed A, Buch T, Waisman A, Virgin HW 4th. Gamma interferon blocks gammaherpesvirus reactivation from latency in a cell type-specific manner. J Virol. 2007;81(11):6134-40. PMCID:PMC1900319 PMID:17360749

Tibbetts SA, Suarez F, Steed AL, Simmons JA, Virgin HW 4th. A gamma-herpesvirus deficient in replication establishes chronic infection in vivo and is impervious to restriction by adaptive immune cells. Virology. 2006;353(1):210-9. PMID:16797052

Steed AL, Barton ES, Tibbetts SA, Popkin DL, Lutzke ML, Rochford R, Virgin HW 4th. Gamma interferon blocks gammaherpesvirus reactivation from latency. J Virol. 2006;80(1):192-200. PMCID:PMC1317536 PMID:16352543

Last Updated: 12/30/2020 4:35:28 PM

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