Inhibition of CD38 to Mitigate Senescence in Lung Ischemia Reperfusion Injury to Improve Viability of Donor Lung Grafts
Description: Lung transplantation is the only life-saving therapy for many patients with advanced lung disease, yet fewer than 20% of donated lungs are ultimately used. A major barrier is the poor performance of older donor lungs, which are increasingly common as the population ages. These grafts are highly vulnerable to ischemia–reperfusion injury (IRI) and primary graft dysfunction (PGD), conditions that affect up to one-third of recipients and significantly reduce survival. No FDA-approved therapies exist to prevent these injuries, leaving organ scarcity as a critical unmet need. Our preliminary data identify CD38 as a key driver of lung injury. CD38 expression rises in aged and stressed lungs, leading to loss of cellular energy and activation of inflammatory signaling that disrupts the lung’s barrier. In mouse models, genetic deletion of CD38 reduces injury, preserves endothelial integrity, and improves function after IRI. Pharmacologic inhibitors of CD38, including quercetin, fisetin, and 78c, show similar protective effects. These findings support CD38 as a mechanistic link between aging, senescence, and transplant injury. This project will pursue three aims: (1) define how CD38 regulates endothelial injury and immune signaling during lung IRI, (2) test whether CD38 inhibition improves function in aged donor lungs using murine and rat transplant-relevant models, and (3) evaluate efficacy and safety in human precision-cut lung slices from older donors. By clarifying the role of CD38 and testing clinically relevant inhibitors, this work directly addresses the underuse of older donor lungs. Success would expand the donor pool, shorten waiting times, and improve survival for patients awaiting transplant. More broadly, targeting CD38 may provide a new strategy for treating acute lung injury in other settings. This proposal advances the American Heart Association’s mission by developing innovative therapies to extend healthy life for patients with life-threatening cardiopulmonary disease.
Funder: American Heart Association
Amount: $163,900
Funding type: fellowship
Funder scheme: Postdoctoral Fellowship
Start date: 2026-07-01
End date: 2028-06-30
Investigators: Dhiaeddine Djabri, Dhiaeddine Djabri
Institution: The Ohio State University
Funded outputs count: 0
Funder award ID: 26POST1563337
OpenAlex ID: G41632578