Targeting the NuRD protein complex in neuroblastoma and multiple myeloma
Cancer-specific dependencies within the NuRD chromatin remodeler complex: new targets and chemical tools
Researchers are creating lab tools and drug leads to exploit weak spots in the NuRD protein complex to kill neuroblastoma and multiple myeloma cells with specific HDAC1 or HDAC2 gene losses.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Scripps Research Institute, the NIH-funded |
| Lab location | 1 site (La Jolla, United States) |
| Project ID | NIH-11247951 on NIH RePORTER |
What this research studies
The team found that when tumors lose one copy of HDAC1 or HDAC2, they become highly dependent on the remaining HDAC and other NuRD complex subunits. They will use gene editing (CRISPR), targeted protein degradation (dTAG), and chemical probe development to disrupt NuRD and identify which subunits are essential for tumor survival. Lab work will test these vulnerabilities in cancer cells and develop small molecules that selectively destroy cancer cells with those genetic deletions. The goal is to generate candidate molecular tools and drug leads that could guide future targeted treatments for patients with these specific tumor profiles.
Who could benefit from this research
Good fit: Patients whose tumors are diagnosed as neuroblastoma or multiple myeloma and that carry hemizygous deletions of HDAC1 or HDAC2 would be the most relevant candidates for future therapies from this work.
Not a fit: Patients whose cancers do not have HDAC1/HDAC2 deletions or who have unrelated cancer types are unlikely to benefit directly from this research.
Why it matters
Potential benefit: If successful, this work could produce targeted therapies that selectively kill tumors with HDAC1 or HDAC2 deletions while sparing normal cells.
How similar studies have performed: Related approaches using targeted protein degradation and synthetic-lethality concepts have shown promising preclinical results, but they remain largely unproven as approved treatments for these specific genetic vulnerabilities.
Where this research is happening
La Jolla, United States
- Scripps Research Institute, the — La Jolla, United States (Active)
Researchers
- Principal investigator: Erb, Michael a — Scripps Research Institute, the
- Study coordinator: Erb, Michael a
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.