How DNA-repair changes let some blood stem cells expand after DNA-damaging exposures
Project 2: The role of the DNA damage response in clonal competition following genotoxic stress
This work looks at whether mutations in DNA-repair genes let certain blood stem cells grow out after things like chemotherapy or cigarette smoke, raising blood cancer risk.
Quick facts
| Grant type | P01 program project |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Baylor College of Medicine NIH-funded |
| Lab location | 1 site (Houston, United States) |
| Project ID | NIH-11378274 on NIH RePORTER |
What this research studies
Researchers will use mouse models that mix normal and mutant blood stem cells to see which DNA damage response (DDR) gene changes let cells outcompete their neighbors after exposure to DNA-damaging agents like cisplatin or cigarette smoke. The team will compare several CH-associated mutations (for genes such as PPM1D, TP53, ATM, CHEK2, and SRCAP) in a novel 5x mosaic model to see which mutations gain advantage. They will study resulting mutation patterns, stem cell behavior, and steps toward malignant transformation to link exposures to clonal hematopoiesis and leukemia risk. Findings will guide how prior treatments or exposures may select for dangerous clones and inform future patient monitoring or prevention strategies.
Who could benefit from this research
Good fit: Individuals with known clonal hematopoiesis mutations, a history of chemotherapy, or heavy cigarette smoke exposure would be the most relevant patient groups for related clinical follow-up or sample donation.
Not a fit: People without blood stem cell mutations or without prior exposure to DNA-damaging treatments are unlikely to receive direct benefit from this project in the near term.
Why it matters
Potential benefit: If successful, this work could help identify who is at higher risk of therapy- or exposure-related blood cancers and inform safer treatment or monitoring strategies.
How similar studies have performed: Prior animal and genetic studies have shown DDR mutations can drive clonal expansion after chemotherapy, and this project builds on those established findings.
Where this research is happening
Houston, United States
- Baylor College of Medicine — Houston, United States (Active)
Researchers
- Principal investigator: Nakada, Daisuke — Baylor College of Medicine
- Study coordinator: Nakada, Daisuke
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.