Why mutated blood stem cells expand with age
Molecular mechanism underlying clonal expansion of hematopoietic stem cells
Researchers are looking at how infections and chronic inflammation help p53-mutated blood stem cells grow in older people with clonal hematopoiesis.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Northwestern University NIH-funded |
| Lab location | 1 site (Chicago, United States) |
| Project ID | NIH-11378301 on NIH RePORTER |
What this research studies
This project explores how aging, infections, and chronic inflammation allow p53-mutated hematopoietic stem cells to outcompete normal blood stem cells and lead to clonal hematopoiesis and sometimes myelodysplastic syndromes (MDS). The team uses lab models, including mice carrying TP53 mutations, and molecular tools such as ATAC-seq and epigenetic profiling to study chromatin and gene regulation in affected stem cells. They measure inflammasome activation and proinflammatory cytokines to see how infection-driven inflammation gives mutant cells a competitive edge. The researchers will test interventions that block the NLRP1 inflammasome or modify EZH2-related epigenetic marks to see if these approaches prevent mutant cell expansion.
Who could benefit from this research
Good fit: People with age-related clonal hematopoiesis, especially those with TP53 mutations detected in blood tests, would be most relevant for this research.
Not a fit: People without clonal hematopoiesis or whose blood shows different non-TP53 mutations may not benefit from the specific findings.
Why it matters
Potential benefit: Could identify ways to stop or slow mutant blood stem cells from progressing to MDS or other blood cancers.
How similar studies have performed: Previous lab and animal studies have shown mutant p53 and inflammation can drive clonal expansion, but translating those findings into clinical prevention strategies remains largely untested.
Where this research is happening
Chicago, United States
- Northwestern University — Chicago, United States (Active)
Researchers
- Principal investigator: Liu, Yan — Northwestern University
- Study coordinator: Liu, Yan
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.