Protecting donor hearts by boosting a natural Irg1/itaconate pathway
Targeting Immune-Responsive Gene 1 (Irg1) and Itaconate for Cardioprotection of the Donor Heart for Transplantation
This project aims to use a known drug to raise a protective chemical (itaconate) in donor hearts so they survive storage and work better after transplant for people needing a new heart.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Mayo Clinic Rochester NIH-funded |
| Lab location | 1 site (Rochester, United States) |
| Project ID | NIH-11141004 on NIH RePORTER |
What this research studies
If I'm waiting for a heart transplant, this work is trying to make donor hearts more resilient during storage and after implantation. The team is using the FDA‑approved drug valproic acid (VPA) to increase Irg1 activity and production of the anti‑inflammatory metabolite itaconate. In mice they add VPA to preservation solutions and test hearts with ex‑vivo perfusion and transplant models to see if function and ischemic tolerance improve. They also study antioxidant signaling (Nrf2) and chromatin changes to understand how the protection works and prepare for translation to human donor heart preservation.
Who could benefit from this research
Good fit: People listed for or awaiting heart transplantation, or those at high risk for primary graft dysfunction, would be the likely candidates for future human trials.
Not a fit: Patients who are not receiving a donor heart, or whose problems are unrelated to preservation injury (for example chronic rejection or noncardiac illness), would be unlikely to benefit directly from this approach.
Why it matters
Potential benefit: If successful, this approach could lower the rate of primary graft dysfunction and increase the number of usable donor hearts for transplant patients.
How similar studies have performed: Preclinical mouse studies by the team show improved donor heart function with VPA‑driven Irg1/itaconate signaling, but human testing of this preservation strategy has not yet been done.
Where this research is happening
Rochester, United States
- Mayo Clinic Rochester — Rochester, United States (Active)
Researchers
- Principal investigator: Tang, Paul — Mayo Clinic Rochester
- Study coordinator: Tang, Paul
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.