How DNA packaging affects repair of single‑strand DNA damage
Epigenetic mechanisms controlling single-stranded DNA lesion sensitivity and mutagenesis
This research looks at how a chromatin protein called macroH2A1 and its splice forms change repair of single‑strand DNA damage that can lead to cancer and affect responses to certain chemotherapy and PARP inhibitor treatments.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Johns Hopkins University NIH-funded |
| Lab location | 1 site (Baltimore, United States) |
| Project ID | NIH-11139495 on NIH RePORTER |
What this research studies
If you have cancer, researchers at Johns Hopkins will study how a histone variant called macroH2A1 and its two splice forms influence repair of single‑stranded DNA lesions that drive mutations. They will use cellular and molecular experiments, biochemical binding tests, and analyses of cancer-derived samples to see how macroH2A1.1 interacts with PAR (poly‑ADP‑ribose) and controls repair pathways. The team will examine how macroH2A1 levels alter sensitivity to drugs that cause these lesions, such as topoisomerase I inhibitors and alkylating agents, and how that intersects with PARP inhibitor responses. Results may point to biomarkers or strategies to make existing therapies work better for some patients.
Who could benefit from this research
Good fit: Ideal candidates would be people with cancers treated with topoisomerase I inhibitors, alkylating agents, or PARP inhibitors, or patients willing to donate tumor samples for research.
Not a fit: Patients without cancer or whose tumors are driven by unrelated mechanisms are unlikely to receive direct benefit from this project.
Why it matters
Potential benefit: If successful, this work could help predict which tumors will respond to PARP inhibitors or DNA‑damaging chemotherapy and suggest ways to sensitize resistant cancers.
How similar studies have performed: PARP inhibitor therapies and the importance of single‑stranded DNA repair are well established in cancer care, but the specific role of macroH2A1 splice isoforms in this context is a newer and less‑tested area.
Where this research is happening
Baltimore, United States
- Johns Hopkins University — Baltimore, United States (Active)
Researchers
- Principal investigator: Oberdoerffer, Philipp — Johns Hopkins University
- Study coordinator: Oberdoerffer, Philipp
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.