Associate Professor
Scientific Director, Facility for Infectious Disease and Epidemic Research (FINDER)

Research Summary

It is now well established that hijacking of host-cell biosynthetic pathways by human enveloped viruses is a shared molecular event essential for the viral life cycle. The next frontier is identifying the specific and common critical host-cell pathways that are hijacked by those pathogenic human viruses of great concern around the world. This will enable development of global antiviral strategies that will catalyze the creation of therapeutics with novel mechanisms of action that target critical host components that are essential to infection and disease. Developing novel host-directed therapeutic agents will have a dramatic impact globally by providing desperately needed broad-spectrum therapeutics against drug-resistant viruses that are continuously eroding the therapeutic armamentarium, leaving fewer or no alternative antiviral agents available.

The research programs of my laboratory are based on my breakthroughs in the field of broad-based antiviral therapeutics (Senior, K., 2000. Early steps towards a broad-based antiviral drug. The Lancet 355: 729). My lab is exploring in detail how our novel therapeutic approaches can combat human viral infections using our recently identified protein-based inhibitors directed at those host-cell proteases and viral proteases that are essential for the virus life cycle. I am now expanding the scope of my research to include our newly discovered marine natural products, natural broad-spectrum antiviral peptides, and therapeutic microRNAs. My team is developing and applying novel efficacious broad-based antiviral agents against important human enveloped viruses of major public health concern in Canada and around the world [e.g., hepatitis C virus (HCV), West Nile virus (WNV), dengue virus (DNV), HIV-1, and influenza A virus (InfA)]. My research programs are supported by the Canadian Institutes of Health Research (CIHR) and infrastructure funds from the Canada Foundation for Innovation (CFI) and British Columbia Knowledge Development Fund (BCKDF).

The results of my research programs have allowed my team (i) to generate new antiviral agents for dissecting the biological functions of viral and host-cell enzymes necessary for the virus replication and life cycle, (ii) to define the biological impact of new classes of antiviral agents on viral infection and disease, (iii) to discover new exosome-associated biomarkers for viral diseases, and (iv) to provide insights into new therapeutic avenues for treating and diagnosing important viral diseases such as hepatitis C, epidemic viral encephalitis, AIDS, and infectious respiratory diseases.

Bio

B.Sc., Université de Montréal (1988)
M.Sc., Clinical Research Institute of Montréal (1991)
Ph.D., Clinical Research Institute of Montréal (1995)
MRC Postdoctoral, Vollum Institute, Oregon Health Sciences University (1995-99)

Teaching

Founder and scientific advisor of Rising Stars of Research, National Undergraduate Science Research Poster Competition, (2008-2010).

Awards

UBC Science Achievement Award (2010)
Fisher Scientific Award recipient (2003) [Canadian Society of Microbiologists (CSM)]
CIHR/Health Canada Research Initiative on Hepatitis C New Investigator Award (2000-2005)
Peter Wall Institute for Advanced Studies Early Career UBC Award (2000-2001)

Publications

Selected Publications

  1. Emma-Kate Loveday, Sandra Diederich, John Pasick, and François Jean (2014) Human microRNA-24 modulates highly pathogenic avian-origin H5N1 influenza A virus infection in A549 cells by targeting secretory pathway furin. Journal of General Virology (in press)
  2. Plumb AW, Patton DT, Seo JH, Loveday EK, François Jean, Ziegler SF, Abraham N (2012) Interleukin-7, but not thymic stromal lymphopoietin, plays a key role in the T cell response to influenza a virus. PLoS One 7(11):e50199. doi: 10.1371/journal.pone.0050199.
  3. Anthony Khong, Roberto Forestieri, David E. Williams, Brian O. Patrick, Andrea Olmstead, Victoria Svinti, Emily Schaeffer, François Jean, Michel Roberge, Raymond J. Andersen, and Eric Jan (2012) A Daphnane Diterpenoid isolated from Wikstroemia Polyantha induces an inflammatory response and modulates miRNA activity. PLoS ONE 7(6): e39621. doi:10.1371/journal.pone.0039621
  4. C. A. Thomson, Y. Wang, L. M. Jackson, M. Olson, W. Wang, A. Liavonchanka, L. Keleta, V. Silva, S. Diederich, R. B. Jones, J. Gubbay, J. Pasick, M. Petric, François Jean, V. G. Allen, E. G. Brown, J. M. Rini and J. W. Schrader (2012) Pandemic H1N1 Influenza Infection and Vaccination in Humans Induces Cross-Protective Antibodies that Target the Hemagglutinin Stem. Front. Immun.3:87. doi: 10.3389/fimmu.2012.00087
  5. Emma-Kate Loveday, Victoria Svinti, Sandra Diederich, John Pasick, and François Jean (2012) Temporal and strain-specific host microRNA molecular signatures associated with swine-origin H1N1 and avian-origin H7N7 influenza A virus infection. Journal of Virology 86:6109-6122
  6. Andrea D. Olmstead, Wolfgang Knecht, Ina Lazarov, Surjit B. Dixit, and
    François Jean. (2011) Human subtilase SKI-1/S1P is a master regulator of theHCV life cycle and a potential host cell target for developing indirect-acting antiviral agents. PLoS Pathogens 2012 Jan;8(1):e1002468. Epub 2012 Jan 5.
  7. Martin, M., Condotta, S., Fenn, J., Olmstead, A., Jean, F. (2011) In-cell selectivity profiling of membrane-anchored and replicase-associated hepatitis C virus NS3-4A protease reveals a common, stringent substrate recognition profile. Biological Chemistry. 2011 Jul 13. [Epub ahead of print]
  8. Hoshino, A., Kowalska, D., Jean, F., Lazure, C., Lindberg, I. (2011)
 Modulation of PC1/3 activity by self-interaction and substrate binding Endocrinology. 152: 1402-11.
  9. Condotta, S., Martin, M. M., Boutin, M., Jean, F. (2010) Detection and in-cell selectivity profiling of the full-length West-Nile virus NS2B/NS3 serine protease using membrane-anchored fluorescent substrates. Biological Chemistry. 391:549-59.
  10. Vandekerckhove J. (2007) Paper of the Year 2006: Awarded to Pamela Hamill. Biological Chemistry. 388: 875.
  11. Hamill, P., Hudson, D., Kao, R., Chow, P., Raj, M., Xu, H., Richer, M., and Jean, F. (2006) Development of a red-shifted fluorescence-based assay for SARS-coronavirus 3CL protease: Identification of a novel class of anti-SARS agents from the tropical marine sponge Axinella corrugata. Biological Chemistry. 387: 1063-74.
  12. Martin, M., Jean, F. (2006) Single-cell resolution imaging of membrane-anchored hepatitis C virus NS3/4A protease activity. Biological Chemistry. 387: 1075-80.
  13. Hamill, P., Jean, F. (2005) Enzymatic characterization of membrane-associated hepatitis C Virus NS3-4A heterocomplex serine protease activity expressed in human cells. Biochemistry. 44: 6586-96
  14. Richer, M., Keays, C., Waterhouse, J., Minhas, J., Hashimoto, C., Jean, F. (2004) The Spn4 gene of Drosophila encodes a potent furin-directed secretory pathway serpin. Proc. Natl. Acad. Sci. U.S.A. 101: 10560-10565.
  15. Richer, M., Juliano, L., Hashimoto, C., and Jean, F. (2004) Serpin mechanism of hepatitis C virus NS3 protease inhibition: Induced fit as a mechanism for narrow specificity. J. Biol. Chem. 279:10222-10227.
Office Phone
6048220256
Office
3559