RESEARCH

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.

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SUPER-WARRIOR ELF1

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.

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MEETING OF THE BUGS

During influenza virus infections, immune-mediated changes in the airways provide a breeding ground for certain bacteria. Bacterial superinfection can drastically worsen influenza disease outcome.
We seek to understand the opposite scenario: how members of the respiratory microbiota, exemplified by Staphylococcus aureus, help influenza viruses colonize the respiratory tract.

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.

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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. 


NANO-AIRWAYS

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.

Want to learn more about our research projects?

 

Dittmann laboratory
Alexandria Center for Life Sciences, West Tower
430 E 29th Street, room 313
New York, New York 10016
USA

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