Department of Cell Biology

Tom Hobman


Tom Hobman

Ph.D., University of British Columbia

Professor
Office: 780-492-6485
tom.hobman@ualberta.ca

Awards

  • Canada Research Chair in RNA Viruses and Host Interactions

Research Interests

There are two major projects in the laboratory

Project I: 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. Finally, we have expanded our studies on emerging viruses to include the mosquito-transmitted pathogens Chikungunya and Mayaro viruses. 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  
  Super-resolution image of Zika virus replication complex (red) in mammalian cell 24 hours post-infection  

 

Project II: Regulation of RNA interference pathways 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 silencing effector complexes. Ago2 has endonuclease activity and is the most abundant and ubiquitously expressed Argonaute isoform. Our research is focused on understanding how Ago2 activity is regulated under normal and disease conditions. 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, Canada Research Chairs, IC-IMPACTS, Canada Research Chairs, Canada Foundation for Innovation and Alberta Innovates Health Solutions.


Selected Publications

Atienza, B., Jensen, L., Noton, S. Ansalem, A.K., Hobman, T., Fearns, R., Marchant, David, D. and West, F. (2018) Dual Catalytic Synthesis of Antiviral Compounds Based on Metallocarbene-Azide Cascade Chemistry. J Org Chem (in press).

Wong, C.P., Xu, Z., Power, C. and Hobman, T.C.  (2018) Target elimination of peroxisomes during viral infection: Lessons from HIV and other viruses. DNA and Cell Biology 37: 1-5. 

Airo, A.M., Urbanowski, M.D., Lopez-Orozco, J., You, JH, Skene-Arnold, T.D., Holmes, C., Yamshchikov, V., Malik-Soni. N., Frappier, L., and Hobman, T.C. (2018) Expression of flavivirus capsids enhance the cellular environment for viral replication by activating Akt-signalling pathways. Virology 516: 147-157. 

Hou, S., Kumar, A., Airo, A.M., Xu, Z., Stryapunina, I., Wong, C.P., Branton, W., Tchesnokov, E., Gotte, M., Power, C., Hobman, T.C. (2017) Zika virus employs multiple strategies to hijack stress and modulate host stress response. J Virol 91: 1-29.

This article was selected by the editors for inclusion in "Spotlight," a feature in the Journal that highlights research articles of significant interest from the current issue. 

Xu, Z., Asahchop, E., Branton, W.G., Gelman, B.B., Power, C. and Hobman, T.C. (2017) MicroRNAs upregulated during HIV infection target peroxisome biogenesis factors: Implications for virus biology, disease mechanisms and neuropathology. PLoS Pathogens Jun 8;13(6):e1006360. doi: 10.1371/journal.ppat.1006360.

Reid, C.R. and Hobman, T.C. (2017) The nucleolar helicase DDX56 redistributes to West Nile virus assembly sites. Virology 500:169-177. doi: 10.1016/j.virol.2016.10.025.

Kumar, A., Hou, S., Airo, A.M., Limonta, D., Mancinelli, V., Branton, W., Power, C., Hobman, T.C. (2016) Zika virus inhibits type-I interferon production and downstream signaling. EMBO Rep 17 (12):1766-1775.

You, J., Hou, S., Malik-Soni, N., Xu, Z., Kumar, A., Rachubinski, R.A., Frappier, L., andHobman, T.C. (2015) Flavivirus infection impairs peroxisome biogenesis and early anti-viral signaling.J. Virol89: 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 responseNature Chem Biol11: 988-93. doi: 10.1038/nchembio.1940.

Lopez-Orozco, J., Pare, J.M., Holme, A.L., Chaulk, S.G., Fahlman, R.P. andHobman, 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. andHobman, T.C. (2015) The Virus-host Interplay: Biogenesis of +RNA Replication Complexes.Viruses7: 4385-4413. doi: 10.3390/v7082825.

Willows, S., Ilkow, C.S. andHobman, T.C. (2014) Phosphorylation and membrane-association of the Rubella virus capsid protein is important for its anti-apoptotic function.Cell Micro16: 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 Res1833: 2673-2681.

Urbanowski, M.D. andHobman, 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. andHobman, T.C. (2013) Hsp90 co-chaperones p23 and FKBP4 physically interact with hAgo2 and activate RNAi-mediated silencing in mammalian cells.Mol Biol Cell24: 2303-2310.

Xu, Z. andHobman, T.C. (2012) The helicase activity of DDX56 is required for infectivity of West Nile virus particles.Virology433: 226-235.

Xu, Z., Waeckerlin, R., Urbanowski, M.D., van Marle, G. andHobman, T.C. (2012) West Nile virus infection causes endocytosis of a specific subset of tight junction membrane proteins.PLoS One7:e37886. Epub 2012 May 24.

Ilkow, C., Goping, I.S., andHobman, T.C. (2011) The Rubella Virus Capsid is an Anti-Apoptotic Protein that Attenuates the Pore-Forming Ability of Bax.PLoS Pathogens7: ppat.1001291.

Xu, Z., Anderson, R. andHobman, 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. andHobman, T.C. (2010) The kinesin Cut7 regulates the size and morphology of Argonaute complexes.Traffic11: 25-36.

Ilkow, C., Weckbecker, D., Maeir, S., Beatch, M. D., Goping, I.S., Herrmann, J., andHobman, T. C. (2010) The Rubella virus Capsid inhibits mitochondrial import.J. Virol84: 119-30.

Pare, J., Tahbaz, N., López-Orozco, J., LaPointe, P., Lasko, P. andHobman, T. C.(2009) Hsp90 Regulates the Function of Argonaute 2 and its Recruitment to Stress Granules and P-bodiesMol. Biol. Cell20: 3273-84.