Project Grant R01HL153122

This $693,942 National Institutes of Health National Heart Lung and Blood Institute Project Grant funds research at Northwestern University aimed at elucidating epigenetic modifiers of regulatory T cell function following viral pneumonia. The goal is to establish causal links between DNA methyltransferase activity, the DNMT adapter UHRF1, and DNA hypermethylation signatures in regulatory T cells during aging and their impaired reparative function after severe viral pneumonia.

Through three specific aims, the researchers will use murine models, a translational human case-control study, and computational platforms to determine whether DNMT activity or UHRF1 induce DNA hypermethylation in regulatory T cells during normal and premature aging, impairing their pro-recovery transcriptional programs and function following influenza. They will also seek to associate alveolar regulatory T cell DNA methylation signatures, age, and 30-day mortality outcomes in patients with severe influenza A or COVID-19 viral pneumonia. The work funded through September 14, 2021 seeks to enable development of pro-recovery therapeutic approaches for severe influenza, COVID-19, and other causes of acute respiratory distress syndrome in older patients.