Dr. Yount’s laboratory aims to define cellular defense mechanisms active against viral pathogens. In particular, several proteins induced by the interferon family of cytokines inhibit influenza virus infection, yet individual interferon-induced proteins have not been successfully targeted for use in antiviral therapies due to challenges in understanding
the molecular mechanisms by which such proteins inhibit infection as well as a lack of knowledge regarding their cellular regulation. Dr. Yount’s laboratory focuses on understanding post-translational modifications (PTMs) of immune system proteins as PTMs control protein activity and are tightly regulated by cellular enzymes. For example, lipid post-translational modifications, such as palmitoylation, can affect trafficking, clustering, and activity of individual proteins. Indeed, the interferon-induced transmembrane protein 3 (IFITM3) potently inhibits influenza virus infection and its activity is differentially regulated by at least two PTMs including palmitoylation. Dr. Yount’s laboratory is seeking to define the molecular mechanisms by which palmitoylated IFITM3 inhibits influenza virus and to identify the cellular enzymes that transfer PTMs onto IFITM3. These enzymes represent exciting targets for manipulation of cell biology for enhancing or decreasing the activity of this critical antiviral protein. Using cutting edge chemical reporter technology for studying lipid PTMs and highly sensitive mass spectrometry, the laboratory is also defining additional modes of regulation for other immunomodulatory proteins toward the goal of improving microbial infection treatment and prevention approaches.