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研究领域

My program at the NML is focused on the pathogenesis of respiratory viruses, primarily the influenza virus with emphasis on viral molecular determinants of virulence and host factors that contribute to severe disease. Viruses of particular interest include the avian H5N1 and 1918 pandemic viruses that are highly pathogenic in humans and animal models of infection. Our approaches emphasize techniques in molecular virology including reverse genetics to rescue genetically modified viruses generated entirely from cloned copies of the viral genes. The lab uses similar approaches to examine the biological properties and determinants of virulence of the SARS coronavirus using an infectious clone of the virus constructed in my laboratory. We are also interested in the design and evaluation of conventional and experimental vaccines for influenza and other viral diseases. This work is done in collaboration with Dr. Gary Kobinger in the Special Pathogens Program at NML. In our conventional vaccine program we are developing methods and reagents required for rapid vaccine development that would be used in the event of a sudden appearance of new pandemic influenza virus. Our other interests include the development of novel vaccine strategies and vectors for vaccine delivery and approaches to optimize immunological responses to vaccination.

近期论文

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Takada, A., K. Fujioka, M. Tsuiji, A. Morikawa, N. Higashi, H. Ebihara, D. Kobasa , H. Feldmann, T. Irimura , and Y. Kawaoka. 2004. A Human Macrophage C-Type Lectin Specific for Galactose and N -Acetylgalactosamine Promotes Filovirus Entry. J Virol. 78: 2943-2947. Kobasa, D. , Takada, A., Shinya, K., Hatta, M., Halfmann, P., Theriault, S., Suzuki, H., Nishimura, H., Mitamura, K., Sugaya, N., Usui, T., Murata, T., Maeda, Y., Watanabe, S., Suresh, M., Suzuki, T., Suzuki, Y., Feldmann, H., Kawaoka, Y. (2004) Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature 431: 703-707. V. Bowes, K. Sojonky, S. K. Byrne, Y. Li, D. Kobasa , T. Booth, and M. Paetzel. (2004) Novel Avian Influenza H7N3 Strain Outbreak, British Columbia . Emerg. Inf. Dis. 10: 2192-2195. T. F. Booth, B. Kournikakis, N. Bastien, J. Ho, D. Kobasa , L. Stadnyk, Y. Li, M. Spence, S. Paton, B. Henry, B. Mederski, D. White, D. Low, A. McGeer, A. Simor, M. Vearncombe, J. Downey, F. B. Jamieson, P. Tang, F. Plummer. (2005) Airborne Detection of SARS-coronavirus and environmental contamination in SARS outbreak units. J. Infect. Dis. , 191: 1472-1477. Neumann, G., Ebihara, H., Takada, A., Noda, T., Kobasa, D ., Jasenosky, L.D., Watanabe, S., Kim, J.H., Feldmann, H. and Kawaoka, Y. (2005) Ebola virus VP40 late domains are not essential for viral replication in cell culture. J Virol . 79: 10300-10307. Darwyn Kobasa and Yoshihiro Kawaoka. (2005) Emerging Influenza Viruses: Past and Present. Curr. Mol. Med. 5: 791-803. Hideki Ebihara , Ayato Takada , Darwyn Kobasa , Steven Jones , Gabriele Neumann , Steven Theriault , Mike Bray , Heinz Feldmann , and Yoshihiro Kawaoka. (2006) Molecular Determinants of Ebola Virus Virulence in Mice. PLoS Pathog. 2: e73. Qing Ge, Manoj Pastey, Darwyn Kobasa , Piliapan Puthavathana, Christopher Lupfer, Richard K. Bestwick, Patrick L. Iversen, Jianzhu Chen, and David A. Stein. (2006) Inhibition of Multiple Subtypes of Influenza A Virus in Cell Cultures with Morpholino Oligomers. Antimicrobial Agents and Chemotherapy 50: 3724-3733. Darwyn Kobasa, Steven M. Jones, Kyoko Shinya, John C. Kash, John Copps, Hideki Ebihara, Yasuko Maeda -Hatta , Jin Hyun Kim, Peter Halfmann, Masato Hatta, Friederike Feldmann, Judie B. Alimonti, Lisa Fernando, Yan Li, Michael G. Katze, Heinz Feldmann, and Yoshihiro Kawaoka. (2007) Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature 445: 319-323. Laddy, D.J., Yan, J., Corbitt, N., Kobasa, D., Kobinger, G.P., Weiner, D.B. (2007) Immunogenicity of novel consensus-based DNA vaccines against avian influenza. Vaccine 25: 2986-2989. Schwartz, J.A., Buonocore, L., Roberts, A., Suguitan, A., Kobasa, D., Kobinger, G., Feldmann, H., Subbarao, K., and Rose, J.K. (2007) Vesicular stomatitis virus vectors expressing avian influenza H5 HA induce cross-neutralizing antibodies and long-term protection. Virol. May 22; [Epub ahead of print]

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