How DNA-cutting enzymes control antibody and T cell receptor genes
Elucidating Mechanisms of RAG Endonuclease Mediated Feedback Inhibition of V(D)J Recombination
This project looks at how a DNA‑cutting enzyme and the ATM protein help B and T cells make only one working receptor, which could matter for people with immune disorders such as ataxia‑telangiectasia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Children's Hosp of Philadelphia NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11099800 on NIH RePORTER |
What this research studies
Immune cells create antibodies and T cell receptors by cutting and joining gene segments, and this project follows how that cutting is stopped on the second gene copy once the first is successful. The team uses mouse models and lab-grown immune cells to produce and track DNA breaks, measure gene activity, and manipulate ATM and related proteins such as NEMO. They compare normal and ATM-deficient systems to see when both gene copies become active and to pinpoint the signals that enforce single-copy receptor expression. Results could explain immune problems in people with ATM defects and suggest ways to restore proper receptor control.
Who could benefit from this research
Good fit: The most relevant candidates would be people with ATM deficiency or ataxia‑telangiectasia and individuals willing to donate blood samples for immune cell analysis, plus healthy volunteers for comparison.
Not a fit: People whose immune problems arise from causes unrelated to V(D)J recombination or ATM signaling are unlikely to benefit directly from this research.
Why it matters
Potential benefit: If successful, this work could point to ways to prevent or fix improper immune receptor expression in people with ATM-related immune disorders.
How similar studies have performed: Previous mouse and cell studies support ATM's role in limiting dual receptor expression, but the specific signaling route through NEMO and its effects on RAG transcription are novel and less tested.
Where this research is happening
Philadelphia, United States
- Children's Hosp of Philadelphia — Philadelphia, United States (Active)
Researchers
- Principal investigator: Bassing, Craig H — Children's Hosp of Philadelphia
- Study coordinator: Bassing, Craig H
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.