Blocking RIPK1 to protect the gut from graft‑versus‑host disease
Project 2: Inhibition of RIPK1 Mediated Cell Death to Prevent GVHD
Seeing if drugs that block RIPK1 can protect intestinal stem cells and reduce gut graft‑versus‑host disease in people getting donor bone marrow or stem cell transplants.
Quick facts
| Grant type | P01 program project |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Icahn School of Medicine at Mount Sinai NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11191455 on NIH RePORTER |
What this research studies
From my perspective as a patient, researchers are using laboratory-grown gut organoids and mouse transplant models to see whether stopping RIPK1 activity prevents damage to intestinal stem cells that leads to severe gut GVHD. They are testing two RIPK1 inhibitors (Necrostatin‑1s and GNE684) and studying mice with altered RIPK1/RIPK3 to understand how crypts recover and how inflammation changes. The team will examine tissue samples for crypt health, RIPK1 activation, and protective proteins like REG3γ. They will also check whether blocking RIPK1 affects the transplant’s ability to fight leukemia (the graft‑versus‑leukemia effect).
Who could benefit from this research
Good fit: Ideal candidates would be people who have had or are planning to receive an allogeneic bone marrow or stem cell transplant and are at risk for or developing GI GVHD.
Not a fit: People who are not undergoing allogeneic transplantation or whose gut injury is caused by mechanisms unrelated to RIPK1 may not benefit from this approach.
Why it matters
Potential benefit: If successful, this approach could reduce severe gastrointestinal GVHD after allogeneic transplant, lowering complications and transplant‑related deaths.
How similar studies have performed: Preclinical work in organoids and mouse models has shown protection of intestinal stem cells with RIPK1 inhibitors, but this strategy has not yet been proven in patients.
Where this research is happening
New York, United States
- Icahn School of Medicine at Mount Sinai — New York, United States (Active)
Researchers
- Principal investigator: Ferrara, James L. M. — Icahn School of Medicine at Mount Sinai
- Study coordinator: Ferrara, James L. M.
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.