Why some blood stem cells take over with age
Molecular mechanism underlying clonal expansion of hematopoietic stem cells
['FUNDING_R01'] · NORTHWESTERN UNIVERSITY · NIH-11515145
Researchers are looking at whether infections and chronic inflammation help p53‑mutant blood stem cells expand and raise the risk of pre‑cancerous blood disorders in older adults.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | NORTHWESTERN UNIVERSITY (nih funded) |
| Locations | 1 site (CHICAGO, UNITED STATES) |
| Trial ID | NIH-11515145 on ClinicalTrials.gov |
What this research studies
This project studies clonal hematopoiesis, a condition where a single mutated blood stem cell can grow to dominate blood cell production and increase cancer risk. The team focuses on TP53 (p53) mutations and how inflammatory stress from infections activates the NLRP1 inflammasome to give mutant stem and progenitor cells a competitive edge. They combine animal models, molecular assays (including ATAC‑seq and histone modification analyses), and comparisons with human clinical data to map the chain of events from inflammation to clonal expansion. The long‑term aim is to identify ways to block that pathway and prevent progression to myelodysplastic syndromes (MDS).
Who could benefit from this research
Good fit: People most relevant would be older adults with clonal hematopoiesis, especially those whose blood testing shows TP53 mutations or who are being monitored for MDS risk.
Not a fit: People without clonal hematopoiesis or whose blood cells lack TP53 mutations are unlikely to benefit directly from this project.
Why it matters
Potential benefit: If successful, this work could point to treatments or preventive strategies that stop TP53‑mutant clonal hematopoiesis from progressing to myelodysplastic syndromes (MDS).
How similar studies have performed: Previous work showed TP53 mutations can drive clonal expansion via EZH2 and H3K27me3 changes, while linking inflammation and the NLRP1 inflammasome to this process is a newer approach supported by animal data but with limited clinical trial evidence so far.
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.