Federal Project Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded The Ohio State University a Project Grant valued at $1.1 million (obligated dollars) under the Cardiovascular Diseases Research program (CFDA 93.837), effective July 1, 2026, through June 30, 2033. This R35 program investigates the molecular mechanisms underlying immune suppression in Acute Respiratory Distress Syndrome (ARDS) through research on ubiquitin E3 ligases, specifically F-box proteins. The research deliverables include discovery and characterization of immunosuppressive F-box proteins using knockout mouse models and gene transfer approaches, identification of novel F-box substrates targeted for ubiquitin-mediated degradation, and development of small molecule F-box antagonists designed to restore innate immune responses in ARDS models.

The funded research employs multiple experimental methodologies and model systems to accomplish its objectives, including unbiased screening approaches for substrate identification, virtual design and lead optimization of small molecule compounds, and testing in murine models, two-hit immunosuppression models, and an ex vivo isolated human lung system. The ultimate deliverables are novel pharmacologic compounds and a new pathobiological model of lung injury that can serve as a platform for generating therapeutic interventions to address immune suppression in ARDS, a devastating disorder with high mortality for which existing anti-inflammatory approaches have demonstrated limited clinical benefit.