Hobman, Tom - University of Alberta - Department of Medicine

研究领域

There are two major projects in the laboratory Project 1: RNA virus host interactions: RNA viruses infect hundreds of millions of people each year resulting in millions of deaths. A major focus of my laboratory is flaviviruses, which include the human pathogens Zika, Dengue, and West Nile viruses. Unfortunately, other than a limited number of vaccines, there are few treatment options available. We study how proteins encoded by these pathogenic viruses alter anti-viral signaling, transcriptional activity, alternative splicing, and miRNA regulation in host cells. More recently, in collaborative studies, we have been investigating how HIV-induced changes to host miRNA expression profiles affects anti-viral signaling and organelle biogenesis. Through these studies, we expect to identify cellular pathways that are exploited by the viruses to benefit replication. Ultimately, we hope to use this information to develop targets for novel anti-viral therapies. Super-resolution image of Zika virus replication complex (red) in mammalian cell 24 hours post-infection Project 2: RNAi machinery and breast cancer: Regulation by miRNAs and the RNAi pathway affects expression of more than 60-70% of mammalian genes. Accordingly, deregulation of this pathway could alter the expression of a vast array of cellular gene products, ultimately changing the phenotypic properties of that cell (i.e. metastatic transformation). Members of the Argonaute family of proteins bind the miRNA to form the silencing effector complex. Ago2 has endonuclease activity and is the most abundant and ubiquitously expressed Argonaute isoform. It is the only Argonaute required for the maturation of certain miRNAs. Emerging data suggest that Ago2 is an important tumor suppressor in breast cancer. Our research is supported by: Canadian Institutes of Health Research, Canadian Breast Cancer Foundation, Li Ka Shing Institute of Virology, Women & Children’s Health Research Institute, Canada Research Chairs, IC-IMPACTS, National Sciences & Engineering Research Council, Canada Research Chairs, Canada Foundation for Innovation and Alberta Innovates Health Solutions.

近期论文

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Reid, C.R. and Hobman, T.C. (2016) The nucleolar helicase DDX56 redistributes to West Nile virus assembly sites. Virology (in press). Kumar, A., Hou, S., Airo, A.M., Limonta, D., Mancinelli, V., Branton, W., Power, C., Hobman, TC (2016) Zika virus inhibits type-I interferon production and downstream signaling. EMBO Rep e201642627. [Epub ahead of print]. You, J., Hou, S., Malik-Soni, N., Xu, Z., Kumar, A., Rachubinski, R.A., Frappier, L., and Hobman, T.C. (2015) Flavivirus infection impairs peroxisome biogenesis and early anti-viral signaling. J. Virol 89: 12349-61. doi: 10.1128/JVI.01365-15. Selected by editors for inclusion in "Spotlight," a feature in the Journal that highlights research articles of significant interest from the current issue. Singaravelu, R, O’Hara, Shifawn, Jones, DM. Chen, R., Steenbergen, R.H., Kumar, A, Taylor, N.G., Srinivasan, P., Lyn, R.K., Quan, C., Özcelik, D., Nguyen, M-A., Rayner, K.J., Hobman, T., Tyrrell, D.L., Russell, R.S., and Pezacki, J.P. (2015) Oxysterol induced microRNAs regulate antiviral response Nature Chem Biol 11: 988-93. doi: 10.1038/nchembio.1940. Lopez-Orozco, J., Pare, J.M., Holme, A.L., Chaulk, S.G., Fahlman, R.P. and Hobman, T.C. (2015) Functional analyses of phosphorylation events in human Argonaute 2. RNA 21: 2030-8. doi: 10.1261/rna.053207.115. Reid, C.R., Airo, A.M. and Hobman, T.C. (2015) The Virus-host Interplay: Biogenesis of +RNA Replication Complexes. Viruses 7: 4385-4413. doi: 10.3390/v7082825. Willows, S., Ilkow, C.S. and Hobman, T.C. (2014) Phosphorylation and membrane-association of the Rubella virus capsid protein is important for its anti-apoptotic function. Cell Micro 16: 1201-10. Mangala Prasad, V., Willows, S.D., Fokine, A., Battisti, A. J., Sun, S., Plevka, P., Hobman, T.C., Rossmann, M.G. (2013) Rubella virus capsid protein structure and its role in virus assembly and infection. Proc. Natl. Acad. Sci. 110: 20105-20110. Wang, Y., Mercier, R., Hobman, T.C., and LaPointe, P. (2013) Regulation of RNA interference by Hsp90 is an evolutionarily conserved process. Biochim Biophys Acta - Mol Cell Res 1833: 2673-2681. Urbanowski, M.D. and Hobman, T.C. (2013) The West Nile Virus Capsid Protein Blocks Apoptosis through a Phosphatidylinositol 3-kinase-dependent Mechanism. J. Virol. 87: 872-881. Pare, J.M., LaPointe, P. and Hobman, T.C. (2013) Hsp90 co-chaperones p23 and FKBP4 physically interact with hAgo2 and activate RNAi-mediated silencing in mammalian cells. Mol Biol Cell 24: 2303-2310. Xu, Z. and Hobman, T.C. (2012) The helicase activity of DDX56 is required for infectivity of West Nile virus particles. Virology 433: 226-235. Xu, Z., Waeckerlin, R., Urbanowski, M.D., van Marle, G. and Hobman, T.C. (2012) West Nile virus infection causes endocytosis of a specific subset of tight junction membrane proteins. PLoS One 7:e37886. Epub 2012 May 24. Ilkow, C., Goping, I.S., and Hobman, T.C. (2011) The Rubella Virus Capsid is an Anti-Apoptotic Protein that Attenuates the Pore-Forming Ability of Bax. PLoS Pathogens 7: ppat.1001291. Xu, Z., Anderson, R. and Hobman, T.C. (2011) The nucleolar helicase DDX56 is required for assembly of infectious West Nile virions. J. Virol. 85: 5571-80. Pare J.M., Lopez-Orozco J, Hobman T.C. (2011) Live Cell Imaging of Argonaute Proteins in Mammalian Cells. Methods Mol Biol. 725: 161-172. Stoica, C., Park, JS, Pare, J., Willows, S. and Hobman, T.C. (2010) The kinesin Cut7 regulates the size and morphology of Argonaute complexes. Traffic 11: 25-36. Ilkow, C., Weckbecker, D., Maeir, S., Beatch, M. D., Goping, I.S., Herrmann, J., and Hobman, T. C. (2010) The Rubella virus Capsid inhibits mitochondrial import. J. Virol 84: 119-30. Pare, J., Tahbaz, N., López-Orozco, J., LaPointe, P., Lasko, P. and Hobman, T. C. (2009) Hsp90 Regulates the Function of Argonaute 2 and its Recruitment to Stress Granules and P-bodies Mol. Biol. Cell 20: 3273-84.