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Assistant Professor

Contact Information:
Email: skarst@lsuhsc.edu
Office Phone: 318-675-8122
Laboratory Phone: 318-675-8123
Office Fax: 318-675-5764

Education/Training:
Postdoctoral Study, Washington University School of Medicine
Ph.D., Cellular Biology and Biochemistry, 2000, University of Missouri
B.S., Biology, 1995, Southern Illinois University

Major Research Interests: 
Pathogenesis of noroviruses, innate immune responses to norovirus infection, and molecular mechanisms of norovirus replication.

Noroviruses are responsible for significant human disease, causing over 90% of nonbacterial epidemic gastroenteritis worldwide.  Primary human norovirus infection does not elicit lasting protective immunity, a fact that could greatly affect the efficacy of vaccination strategies.  Our long term goal is to elucidate the mechanisms by which noroviruses avoid the induction of protective immunity, ultimately translating this knowledge into successful vaccination approaches.  Little is known regarding the pathogenesis of human noroviruses or the immune responses that control them because there has previously been no small animal model of norovirus infection:  We discovered the first murine norovirus (MNV), MNV-1, and demonstrated its cultivation in macrophages and dendritic cells in vitro. We have now used these unique models to examine norovirus pathogenesis and immunity.  We have determined that MNV-1 is infectious orally and is associated with the induction of diarrhea, confirming the utility of this virus as a model to study human norovirus pathogenesis.  Importantly, we have also determined that primary MNV-1 infection fails to afford protection to re-challenge with homologous virus.  Thus, MNV-1 represents a valuable model with which to dissect the pathophysiological basis for the lack of lasting protection to human norovirus infection.  Our specific hypothesis is that norovirus infection fails to induce protective mucosal immunity because the virus infects mucosal dendritic cells and prevents their full activation.  Specifically, we will determine whether MNV-1 infection directly or indirectly inhibits dendritic cell activation and whether MNV-1 infection stimulates regulatory T cells.  Our ultimate goal is to understand how these effects on mucosal dendritic cells prevent their stimulation of protective norovirus immunity and to translate this information into effective vaccine design. 

Representative Publications:

S.M. Karst, N. Sadeghi, and T.M. Menees.  Cell cycle control of reverse transcriptase activity for the yeast retrotransposon Ty3.  Biochem Biophys Res Comm. 254(3):679 (1999).

 

S.M. Karst, M.I. Rutz, and T.M. Menees.  The yeast retrotransposons Ty1 and Ty3 require the RNA lariat debranching enzyme, Dbr1p, for efficient accumulation of reverse transcripts.  Biochem Biophys Res Comm 268(1):112 (2000).

 

S.M. Karst, C.E. Wobus, M. Lay, J. Davidson, and H.W. Virgin.  STAT1-dependent innate immunity to a Norwalk-like virus.  Science 299:1575 (2003).

 

C.E. Wobus, S.M. Karst, A. Krug, K-O. Chang, S.V. Sosnovtsev, G. Belliot, J.M. Mackenzie, K.Y. Green, and H.W. Virgin.  Replication of a Norovirus in cell culture reveals a tropism for dendritic cells and macrophages. PLOS 2(12): e432 (2004).

 

S.V. Sosnovtsev, G. Belliot, K-O. Chang, V.G. Prikhodko, L.B. Thackray, C.E. Wobus, S.M. Karst, H.W. Virgin, and K.Y. Green.  Cleavage map and proteolytic processing of the murine norovirus nonstructural polyprotein in infected cells.  J Virol 80(16): 7816 (2006).

 

S.M. Mumphrey, H. Changotra, T.N. Moore, E.R. Heimann-Nichols, C.E. Wobus, M.J. Reilly, M. Moghadamfalahi, D. Shukla, and S.M. Karst.  Murine norovirus 1 infection is associated with histopathological changes in immunocompetent hosts, but clinical disease is prevented by STAT1-dependent interferon responses. J Virol 81(7): 3251 (2007).

 

H. Changotra, Y. Jia, T.N. Moore, G. Liu, S.M. Kahan, S.V. Sosnovtsev, and S.M. Karst.  Type I and type II interferon inhibit the translation of murine norovirus proteins. J Virol 83(11): 5683 (2009).

 

G. Liu, S.M. Kahan, Y. Jia, and S.M. Karst. Primary high-dose murine norovirus 1 infection fails to protect from secondary challenge with homologous virus.  J Virol (epub Apr 29, 2009).

 

 

 

 

 


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