DNA copying problems that drive cancer
DNA replication stress in cancer
This project looks at whether blocking a protein called MRE11 can help cancers with BRCA1 or BRCA2 mutations fix dangerous gaps that form when DNA is copied, especially after chemotherapy or PARP inhibitor treatment.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Washington University NIH-funded |
| Lab location | 1 site (Saint Louis, United States) |
| Project ID | NIH-11300189 on NIH RePORTER |
What this research studies
If you have a BRCA1 or BRCA2 mutation, this work looks at how your cancer's DNA copying process can leave single-stranded gaps when treated with platinum drugs or PARP inhibitors. The team uses very high-resolution electron microscopy and single-molecule DNA fiber methods plus lab biochemistry to measure how those gaps form and whether they get repaired. They focus on a process called PRIMPOL-repriming that makes gaps and on the enzyme MRE11 that may over-resect and prevent repair. The researchers will test whether blocking MRE11 restores gap repair in BRCA1-deficient cells, which could explain treatment sensitivity or resistance.
Who could benefit from this research
Good fit: Patients with cancers caused by BRCA1 or BRCA2 mutations, especially those treated with PARP inhibitors or platinum chemotherapy, would be most relevant to this work.
Not a fit: Patients whose cancers do not involve BRCA1/2-related DNA repair defects or who are not treated with PARP inhibitors or platinum drugs are less likely to directly benefit.
Why it matters
Potential benefit: If successful, this could point to new ways to make PARP inhibitors or platinum chemotherapy work better in BRCA-mutant cancers or identify MRE11 as a target to overcome resistance.
How similar studies have performed: Prior research has linked single-stranded DNA gaps to PARP inhibitor response, but targeting MRE11 to restore gap repair is a more recent laboratory approach that remains early-stage.
Where this research is happening
Saint Louis, United States
- Washington University — Saint Louis, United States (Active)
Researchers
- Principal investigator: Vindigni, Alessandro — Washington University
- Study coordinator: Vindigni, Alessandro
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.