Innate Immune Barriers to Respiratory Viruses
Type-I interferons are major innate immune cytokines produced by cells upon viral infection.
Hundreds of interferon-stimulated genes (ISG) execute the antiviral function of interferons, yet for the vast majority the molecular mechanisms remain a mystery.
Our goals are to elucidate fundamental mechanisms of ISG-mediated virus inhibition, understand how specific ISGs confer broad or narrow antiviral protection, and dissect how this virus-host interface affects disease outcome.
We recently identified a novel antiviral ISG, E74-like ETS-transcription factor 1 (ELF1). ELF1 inhibits every virus we have ever tested in the laboratory. We are characterizing how super-warrior ELF1 combats viruses.
ROCK, SCISSORS, VIRUS
This project builds on our discovery that the innate immune system can block viruses by inhibiting proteolytic steps in viral life cycles. We seek to link other host protease inhibitors (rocks), their target proteases (scissors), and viruses, in the context of innate immunity.
BACK FROM THE DEAD
We seek to understand how the ISG DDX60, a DEAD-box family protein, blocks translation of viral mRNAs to proteins.
DDX60 would be the first example of an interferon-stimulated inhibitor that can distinguish viral from host cell translation.
A MOUSE TRANSMISSION MODEL FOR SARS-COV-2
In collaboration with Dr. Mila Ortigoza's lab, we developed an infant mouse model for SARS-CoV-2 transmission which allows us to study which host factors and pathways contribute to successful virus transmission.
AN UNUSUAL LIFESTYLE CHOICE
Staphylococcus aureus, mainly known for colonizing skin and causing soft tissue or blood stream infections, can on occasion also cause deadly necrotizing pneumonia. In collaboration with Dr. Victor Torres's lab, and using our airway epithelial model, we seek to understand what makes S. aureus strains successful in the airway epithelial environment. We will be expanding our studies to include S. aureus / influenza A virus co-infections.
OUR FAVORITE TOY
The laboratory uses its own high-content imaging microscope CX7 to monitor viral infection and pathogenesis in sub-cellular resolution. Automated cell scoring algorithms allow for image analyses in statistically significant numbers of cells.
Conventional tissue culture systems lack some cellular factors that specific viruses require to complete their life cycles. Polarized human airway epithelial cultures ("nano-airways") provide these factors, but were previously not amenable to genetic manipulation.
We established a novel protocol to generate "nano airways" that can express transgenes, and we use them to study viral-host interactions in a physiologically relevant environment.
In March 2020 we started working with SARS-CoV-2 in our BSL3 facility. We are supporting industry partners and collaborators without BSL3 access, and are pursuing our own research on SARS-CoV-2 and innate immunity.
Want to learn more about our research projects?