Su/Cherry

Project Title

Defining physiological mechanisms of host antiviral immunity against respiratory viruses by studying patients with life-threatening influenza virus or SARS-CoV-2 infections

NIH Mentor

Helen Su

Penn Mentor

Sara Cherry

Project Details

Using a human patient-centered approach the Su lab has previously identified new primary immunodeficiencies that cause a broad susceptibility to viruses, which generally reflect defective T cell mediated immunity. The lab has more recently applied this approach to studying patients with defects in innate immunity, such as MDA5 deficiency. In collaborations with investigators from across the U.S. and internationally, we are using similar approaches to study patients from two cohorts. The first cohort comprises pediatric patients presenting with life-threatening influenza virus (via PICFLU). The second cohort comprises patients of all ages presenting with life-threatening SARS-CoV-2 infections (via NIAID COVID Consortium and COVID-Human Genetic Effort). Whole genome sequencing of the cohorts, performed through the NIAID, has revealed many candidate gene variants contributing to poor outcome including those potentially impacting type I interferon-driven immunity or other host restriction factors. Through an already established collaboration, potential loss-of-function variants are being functionally screened in the Cherry lab by measuring virus replication in vitro following CRISPR/CAS9 and/or siRNA-mediated gene ablation/editing in a variety of cell lines including relevant respiratory cells. It is envisioned that in this collaborative project, the Ph.D. graduate student will work at both sites to complete screens and follow up the most promising candidates with intensive study using human patient materials, and complementing immunological, molecular/biochemical, and virological experimental approaches to delineate regulatory mechanisms of host antiviral immunity.