Our lab focuses on RNA virus-host interactions. We work on a variety of RNA viruses, including coronaviruses (CoVs), dengue virus, hepatitis C virus (HCV) and influenza virus. Some of our current research interests are below:

Roles of viral glycoproteins in entry and pathogenesis

Viral glycoproteins, such as coronavirus spike and influenza hemagglutinin, mediate entry of these viruses into their target cells, often through interaction with cell surface sugars (glycans) and specific protein receptors. We showed that SARS-CoV-2 infection requires sialic acid for entry via endocytosis, but not at the cell surface (Siwak & LeBlanc et al. (2024) PLoS Pathog.). We are currently investigating the cell entry mechanisms, and potential receptors, of highly pathogenic avian influenza of the H5N1 subtype, which has recently been spreading in mammals and poses a significant pandemic risk.

Interestingly, several viral glycoproteins have been shown to activate the pattern recognition receptor TLR4, triggering induction of pro-inflammatory cytokines and contributing to the ‘cytokine storm’ that is associated with severe viral disease (Halajian & LeBlanc et al. (2022) Front. Microbiol.). Since the classic ligand of TLR4 is bacterial lipopolysaccharide, it is unclear how these viral glycoproteins activate TLR4. We are characterizing the viral and cellular determinants that are required for TLR4 activation by viral glycoproteins, which could inform new therapeutic strategies to counteract viral cytokine storm.

Broad-spectrum host-targeting antivirals

Cyclosporine A (CsA) and thapsigargin (Tg) are naturally occurring molecules that have broad-spectrum activity against a diverse array of viruses. We are characterizing the antiviral mechanism(s) of these molecules against RNA virus infections (HCV, dengue virus, common cold coronaviruses, and influenza A virus). Interestingly, CsA and Tg have several shared features, in that they both induce endoplasmic reticulum stress, modulate cellular lipid metabolism, and prime enhanced antiviral immune responses in infected cells. We are investigating the role of these pathways in the broad antiviral activity of CsA (e.g., Mamatis et al. (2023) Antiviral Res.) and Tg (e.g., Pellizzari-Delano et al. (2026) RSC Chem. Biol.; Tooley et al. (2026) bioRxiv) and characterizing the underlying mechanisms.

Modulation of host responses during RNA virus infection

We study endoplasmic reticulum stress and how this is regulated by various RNA viruses. Viral infection places a burden on the ER, through excessive protein synthesis at the ER and remodelling of ER membranes by HCV and CoV non-structural proteins to form viral replication organelles, which are the site of viral RNA replication. ER stress leads to activation of the unfolded protein response (UPR), comprised of three pathways (ATF6, IRE1 and PERK) that function to restore ER homeostasis through diverse mechanisms. We are studying how these UPR pathways affect HCV and HCoV-229E replication, and how viral proteins modulate the UPR to promote viral infection.

Finally, viruses must overcome host innate immune responses to successfully establish infection. We are currently investigating how viral proteins antagonize various innate immune signalling pathways in human cells to establish chronic infection (e.g., hepatitis C virus) or to spread in a new host species (e.g., H5N1 avian influenza).

Funding support

We are currently supported by grants from NSERC, NFRF-E, and the Canada Biomedical Research Fund (SSHRC). We are grateful to CIHR, CFI, ORF, the J.P. Bickell Foundation, the Banting Research Foundation, and Queen’s University for past funding supporting our work.