Michele Hardy, Associate Professor

Veterinary Molecular Biology P.O. Box 173610 Montana State University Bozeman, MT 59717 (406) 994-6378 mhardy@montana.edu

Research Interests

The Hardy laboratory studies molecular interactions between enteric viruses and host cells. We seek to understand how protein-protein interaction networks regulate both viral gene expression and the host cell genetic response to virus invasion. We study two major viral systems, the rotaviruses and noroviruses.  Current projects in the lab include molecular and proteomic investigations of how rotaviruses modulate cellular antiviral gene expression.

Education

• B.S. Texas A&M University, 1988
• Ph.D. Texas A&M University, 1993

Professional Experience

• 1988-1989 Graduate Teaching Assistant, Clinical Pathology, Department of Veterinary Pathology, Texas A&M University
• 1989-1992 Graduate Teaching Assistant, Veterinary Virology, Department of Veterinary Pathology, Texas A&M University
• 1993-1997 Postdoctoral Associate, Division of Molecular Virology, Baylor College of Medicine, Houston, Texas
• 1997-2002 Assistant Professor, Veterinary Molecular Biology, Montana State University
• 1997-present  Affiliate Associate Professor, Dept of Microbiology, University of Washington, Seattle, WA
• 2002-present  Associate Professor, Veterinary Molecular Biology, Montana State University

Honors and Awards

• 2009 Cox Family Award for Teaching and Creative Scholarship
• 2001 Charles and Nora Wiley Award for Meritorious Research and Creative Activity
• 1996-1997 Postdoctoral fellowship, Division of Molecular Virology, Baylor College of Medicine
• 1994-1996 Postdoctoral fellowship, Division of Gastroenterology and Nutrition, Baylor College of Medicine
• 1991-1993 Gamma Sigma Delta, Honor Society for Agriculture

Extramural Grant Activity

Current research programs on rotavirus and Norwalk virus are funded by competitive grants from the NIH and the USDA/NRI

Selected Publications (since 1995)

1. Hardy, M.E., L.J. White, J.M. Ball, and M.K. Estes. 1995. Specific proteolytic cleavage of recombinant Norwalk virus capsid protein. J. Virol. 69:1639-1648.
2. Hardy, M.E., T. Tanaka, N. Kitamoto, L.J. White, J.M. Ball, X. Jiang, and M.K. Estes. 1996. Antigenic mapping of the recombinant Norwalk virus capsid protein using monoclonal antibodies. Virology. 217:252-261.
3. Hardy, M.E.. and M.K. Estes. 1996. Completion of the Norwalk virus genome sequence. Virus Genes 12(3): 289-292.
4. White, L.J., J.M. Ball, M.E. Hardy, T.N. Tanaka, N. Kitamoto, and M.K. Estes. 1996. Attachment and entry of recombinant Norwalk virus particles in cultured cell lines. J. Virol. 70:6589-6597.
5. LeGuyader, F., M.K. Estes, M.E. Hardy, F.H. Neill, J. Green, D.W.G. Brown, and R.L. Atmar. 1996. Evaluation of a degenerate primer for the PCR detection of human caliciviruses. Arch. Virol. 141:2225-2235.
6. Hardy, M.E., S.F. Kramer, J.J. Treanor, and M.K. Estes. 1996. Human calicivirus genogroup II capsid diversity revealed by sequence analysis of the prototype Snow Mountain Agent. Arch. Virol. 142:1469-1479.
7. Redman, J.A., S.B. Grant, T.M. Olson, M.E. Hardy, and M.K. Estes. 1997. The importance of pore water pH in the transmission of Norwalk virus through porous media studied using recombinant Norwalk virus particles. Env. Sci. and Tech. 31:3378-3383
8. Numata, K., M.E. Hardy, S. Nakata, S. Chiba, and M.K. Estes. 1996. Molecular characterization of morphologically typical human calicivirus Sapporo. Arch. Virol. 142:1537-1552.
9. White, L.J., M.E. Hardy, and M.K. Estes. 1997. Biochemical characterization of a smaller form of recombinant Norwalk Virus capsids. J. Virol. 71:8066-8072.
10. Redman, J.A., S.B. Grant, T.M.Olson, M.E. Hardy, and M.K. Estes. 1997. Filtration of recombinant Norwalk virus particles and bacterophage MS2 in quartz sand: importance of electrostatic interactions. Env. Sci. and Tech. 31:3378-3383
11. Ball, J.M., M.E. Hardy, M.E. Conner, and M.K. Estes. 1997. Oral delivery of recombinant Norwalk virus-like particles induces a systemic and mucosal immune response in mice. J. Virol. 72:1345-1353.
12. Prasad, V.V.V., M.E. Hardy, T. Dokland, J. Bella, M.G. Rossman, and M.K. Estes. 1999. Atomic resolution structure of Norwalk virus capsids. Science 286:287-290.
13. Guo, M., K.O. Chang, M.E. Hardy, Q. Zhang and L.J. Saif. 1999. Cloning and sequencing of the RNA genome of a porcine enteric calicivirus genetically related to Sapporo-like human caliciviruses. J. Virol. 73:9625-9631.
14. Prasad, B.V.V., M.E. Hardy, and M.K. Estes. 2000. Structural studies of recombinant Norwalk capsids. J. Infect. Dis. 181:S317-321.
15. Glass, P.J., L.J. White, J.M. Ball, I. Leparc-Goffart, M.E. Hardy, and M.K. Estes. 2000. Norwalk virus open reading frame 3 encodes a minor structural protein. J. Virol. 74:6581-6591.
16. Hardy, M.E., T.J. Crone, J.E. Brower and Khal : Ettayeb: 2002. Substrate specificity of the Norwalk virus 3C-like proteinase. Virus research in press.
17. Mitzel, D.N., C.M. Weisend, M.W. White and M.E. Hardy. 2002. Translational control of rotavirus gene expression displayed by genes 5 and 6. Submitted
18. Graff, J. W., D.N. Mitzel, C. M. Weisend, M.F. Flenniken and M.E. Hardy. Interferon regulatory factor 3 is a cellular partner of rotavirus NSP1. 2002. J Virol 76: 9545-9550
19. Daughenbaugh K.F., C. Fraser, J.W.B. Hershey and M.E. Hardy. 2003. The genome-linked protein VPg binds eIF3, suggesting its role in translation initiation complex recruitment. EMBO J. 22:1-8
20. Lochridge, V.P. and M.E. Hardy. 2003. Snow Mountain virus genome sequence and virus-like particle assembly. Virus Genes: Virus Genes:26:71-82
21. Ettayebi, K. and M.E. Hardy 2003. The Norwalk virus nonstructural protein p48 binds the SNARE-regulator VAP-A and disrupts secretory vesicle trafficking. J. Virol. 77: 11790-11797.
22. Lochridge, V.P., K.J. Jutila, J.W. Graff, and M.E. Hardy. 2005. Epitopes in the P2 domain of norovirus VP1 involved in virus host cell interactions. J Gen Virol 86: 2799
23. Daughenbaugh, K.F., Wobus, C. and M.E. Hardy. 2006. VPg of murine norovirus binds translation initiation factors in infected cells. Virology J 3:33 doi:10.1186/1743-422X-3-33.
24. Shaneyfelt, M.E., A.D. Burke, M.A. Jutila and M.E. Hardy. 2006. Natural products that reduce rotavirus infectivity identified by a semi high throughput screening assay. Virology J 3:68; doi:10.1186/1743-422X-3-68.
25. Buckner, D., S. Wilson, S. Kurk, M.E Hardy, and M.A. Jutila. 2006. Use of early passage fetal intestinal epithelial cells in semi-high-throughput screening assays: An approach to identify new innate immune system adjuvants. J Biomol Screen. 2006 Aug 21.
26. Graff J.W., J. Ewen, K. Ettayebi, and M.E. Hardy. 2007.  Zinc binding domain of rotavirus NSP1 is required for proteasome-dependent degradation of IRF3 and autoregulatory NSP1 stability. J Gen Virol 88:613
27. Ettayebi, K. and M.E. Hardy.  2008.  Recombinant norovirus-specific scFv inhibit virus-like particle binding to cellular ligands.  Virology J 5:21  doi:10.1186/1743-422X-5-21
28. Graff, J.W. K. Ettayebi, and M.E Hardy.  2009. Rotavirus NSP1 inhibits NFkB activation by inducing proteasome-dependent degradation of Beta-TrCP: A novel mechanism of IFN antagonism. 

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