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Program Director/Principal Investigator (Last, First, Middle): BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Christiane E. Wobus Assistant professor eRA COMMONS USER NAME (credential, e.g., agency login) EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION University of Goettingen, Germany Michigan State University, East Lansing, MI University of Heidelberg, Germany University of Goettingen, Germany Washington University School of Medicine, St. Louis, MO DEGREE (if applicable) Vordiplom MS Ph.D. Vordiplom Postdoctoral Fellow YEAR(s) 1992-94 1994-97 1997-2000 1992-94 2001-2006 FIELD OF STUDY Biology Plant Pathology Virology, viral gene Biology Virology, viral pathogenesis A. Positions and Honors Postionand and Employment 3/2007 - Assistant professor Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI Honors 1997-2000 German Cancer Research Institute PhD fellowship 2002- 2005 Institutional NIH training grant appointment 7/2003 Travel grant – American Society for Virology 7/2004 Travel grant – American Society for Virology 11/2004 Travel grant - Second International Calicivirus Conference 6/2005 Travel grant – American Society for Virology 2005-2006 Postdoctoral fellowship, Midwest Regional Center of Excellence (MRCE) for Biodefense and Emerging Infectious Disease Research 2006 Biological Science Scholar, University of Michigan 11/2007 Travel grant – Third International Calicivirus Conference Professional Societies 2001 – Member, American Society for Virology (Full member since 2007) 2006 – Member, AAAS 2009 Member, AMS B. original peer-reviewed publications 1. Hyde, J.L., Sosnovtsev, S.V., Green, K.Y., Wobus, C., Virgin, H.W., Mackenzie, J.M. (2009) Mouse norovirus replication is associated with virus-induced vesicle clusters originating from membranes derived from the secretory pathway. Journal of Virology 83, 9709-19. PMID: 19587041 2. Perry, J. W., Taube, S., Wobus, C. E. (2009) Murine Norovirus-1 entry into permissive macrophages and dendritic cells is pH-independent. Virus Research 43, 125-9. PMID: 19463729 3. Taube, S., Perry, J. W., Yetming, K., Patel, S. P., Auble, H., Shu, L., Nawar, H. F., Lee, C. H., Connell, T. D., Shayman, J. A., Wobus, C. E. (2009) Ganglioside-linked terminal sialic acid moieties on murine macrophages function as attachment receptors for Murine Noroviruses (MNV). Journal of Virology 83, 4092101. PMID: 19244326 4. Chachu, K. A.,Strong, D. W., LoBue, A. D., Wobus, C. E., Baric, R. S., Virgin, H. W. 4th. (2008) Antibody is critical for the clearance of MNV infection. Journal of Virology 82, 6610-7. PHS 398/2590 (Rev. 11/07) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): PI Name 5. Katpally, U., Wobus, C. E., Dryden, K., Virgin, H. W. 4th, Smith, T. J. (2008) The Structure of Antibody Neutralized Murine Norovirus and Unexpected Differences to Virus Like Particles. Journal of Virology 82, 2079882. 6. Baert, L., Wobus, C. E., Van Coillie, E., Thackray, L. B., Debevere, J., Uyttendaele, M. (2008) Detection of Murine Norovirus 1 using plaque assay, transfection assay and real-time RT-PCR before and after heat exposure. Applied Environmental Microbiology 74, 543-6. 7. Thackray, L. B., Wobus, C. E., Chachu, K. A., Liu, B., Alegre, E. R., Henderson, K. S., Kelley, S. T., Virgin, H. W. 4th (2007) Murine noroviruses comprising a single genogroup exhibit biological diversity despite limited sequence divergence. Journal of Virology 81, 10460-10473. 8. Ward, V. K., McCormick, C. J., Clarke, I. N., Salim, O., Wobus, C. E., Thackray, L. B., Virgin, H. W. 4th, Lambden, P. R. (2007) Recovery of infectious murine norovirus using pol II-driven expression of full-length cDNA. PNAS 104, 11050-11055. 9. Mumphrey, S. M., Changotra, H., Moore, T. N., Heimann-Nichols, E. R., Wobus, C. E., Reilly, M. J., Moghadamfalahi, M., Shukla, D., Karst, S. M. (2007) Murine norovirus 1 infection is associated with histopathological changes in immunocompetent hosts, but clinical disease is prevented by STAT1-dependent interferon responses. Journal of Virology 81, 3251-63. 10. Ward, J.M., Wobus, C. E., Thackray. L. B., Erexson, C. R., Faucette, L. J., Belliot, G., Barron, E. L., Sosnovtsev, S. V., Green, K. Y. (2006) Pathology of immunodeficient mice with naturally occurring murine norovirus infection. Toxicological Pathology 34, 708-15. 11. Sosnovtsev, S. V., Belliot, G., Chang, K. O., Prikhodko, V. G., Thackray, L. B., Wobus, C. E., Karst, S. M., Virgin, H. W., Green, K. Y. (2006) Cleavage map and proteolytic processing of the murine norovirus nonstructural polyprotein in infected cells. Journal of Virology 80, 7816-31. 12. Daughenbaugh, K. F., Wobus, C. E., Hardy, M. E. (2006) Murine norovirus VPg binds translation initiation factors in infected cells. Virol Journal 23;3-33. 13. Wobus, C. E., Thackray, L. B., Virgin, H. W. 4th (2006) Murine norovirus: a model system to study norovirus biology and pathogenesis. Journal of Virology 80, 5104-12. 14. Hsu, C.C., Wobus, C. E., Steffen, E. K., Riley, L. K., Livingston, R. S. (2005) Development of a microsphere-based serologic multiplexed fluorescent immunoassay and reverse transcriptase-PCR assay to detect Murine Norovirus 1 (MNV-1) infection in mice. Clinical and Diagnostic Laboratory Immunology 12, 114551. 15. Wobus, C. E., Karst S. M., Thackray, L. B., Chang, K.-O., Sosnovstev S., Belliot, G., Krug, A., Mackenzie, J. M., Green., K. Y., Virgin, H. W. (2004) Replication of a norovirus in culture reveals a tropism for dendritic cells and macrophages. PLOS Biology 2. e432. 16. Karst S. M.*, Wobus, C. E.*, Lay, M., Davidson, J., Virgin, H. W. (2003) STAT-1 dependent innate immunity to a Norwalk-like virus. Science 299, 1575-1578. 17. Kern, A., Schmidt, K., Leder, C., Müller, O.J., Wobus, C. E., Bettinger, K., Von der Lieth, C. W., King, J. A., and J. A. Kleinschmidt. (2003) Identification of a heparin-binding motif on adeno-associated virus type 2 capsids. Journal of Virology 77, 11072-81. 18. Girod A.*, Wobus C.E.*, Z. Zadori, M. Ried, K. Leike, P. Tijssen, J. A. Kleinschmidt, M. Hallek. (2002) The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity. Journal of General Virology 83, 973-978. 19. Wobus, C. E., Hügle-Dörr, B., Girod, A., Petersen, G., Hallek, M. and J. A. Kleinschmidt. (2000) Monoclonal antibodies against the AAV-2 capsid: epitope mapping and identification of capsid domains involved in AAV-2 - cell interaction and neutralization of AAV-2 infections. Journal of Virology 74, 9281-9293. 20. Girod, A., Ried, M., Wobus, C., Lahm, H., Leike, K., Kleinschmidt, J., Deleage, G., and M. Hallek. (1999) Genetic capsid modifications allow efficient re-targeting of adeno-associated virus type 2. Nature Medicine 5, 1052-1056. 21. Wobus, C. E., Skaf, J. S., Schultz, M. H., and G. A. de Zoeten. (1998) Sequencing, genomic localization and initial characterization of the VPg of pea enation mosaic enamovirus. Journal of General Virology 79, 2023-2025. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page Program Director/Principal Investigator (Last, First, Middle): PI Name 22. Skaf, J. S., Rucker, D. G., Demler, S. A., Wobus, C. E., and G. A. de Zoeten. (1997) The coat protein is dispensable for the establishment of systemic infections by pea enation mosaic enamovirus. Plant Molecular Interactions 10, 929-932. C. Research Support Ongoing Research Support Start-up funds Wobus (PI) 3/2007 Department of Microbiology and Immunology, University of Michigan Medical - School Rackham faculty research grant Wobus (PI) 3/2008 – 3/2010 University of Michigan “Mechanism of norovirus interaction with intestinal monolayers” Goal: The goal of this project is to determine whether murine norovirus crosses the intestinal epithelial monolayer using M cells and/or DCs and identify the mechanism of non-immune IgA mediated MNV transcytosis in an in vitro murine intestinal epithelial model. Role: PI Career Development grant Wobus (PI) 3/2008-2/2010 Great Lakes Regional Center for Excellence in Biodefense and Emerging Infectious Diseases Research NIAID, NIH “Identification of small molecule inhibitors and novel drug targets for noroviruses” Goal: The goal of this project is to identify small molecule inhibitors of norovirus entry and identify the cellular and viral determinants of norovirus transcytosis in an in vitro murine intestinal epithelial model. Role: PI Elizabeth Crosby faculty grant Wobus (PI) 11/2008-10/2009 University of Michigan “The role of sialic acid during murine norovirus infection in vitro and in vivo” Goal: This grant provides salary support to work on a project that aims to elucidate the role of sialic acid containing proteins and lipids during MNV infection of murine macrophages in culture and in a mouse model. Role: PI University of Michigan Wobus (PI) 2/2009-1/2010 2008 Genetics and Genomics Pilot Feasibility Grant Program – 2nd Round, “16S genetic analysis of the gastrointestinal microbiome following enteric norovirus infection” Goal: This project funds the investigation of changes in the intestinal microbiota following norovirus infection using 454 high-throughput sequencing. Role: PI R01 Wobus (PI) 07/24/2009 – 06/30/2013 NIH, NIAID “Mechanisms of norovirus entry” Goal: The aim of this project is to dissect viral and host determinants of murine norovirus entry in culture and in mice. Role: PI PHS 398/2590 (Rev. 11/07) Page Continuation Format Page