Removing mutant blood-cell proteins that cause inherited anemia
Development of selective degradation strategies towards mutant transcription factors
Researchers are developing molecular tools to remove a single faulty blood-cell protein that causes some inherited anemias so healthy blood cell production can be restored.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Icahn School of Medicine at Mount Sinai NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11189227 on NIH RePORTER |
What this research studies
If you have an inherited anemia linked to a KLF1 gene mutation, this project is designing molecular 'degraders' that can find and remove the mutant KLF1 protein while leaving the normal copy intact. The team will build degron modules attached to DNA-targeting motifs based on KLF1/DNA interactions and test how selectively they bind. Work includes biochemical in vitro tests and experiments in cultured blood-forming cells to see whether removing the mutant protein restores normal gene expression. This is a lab-focused development project intended to create a blueprint for future therapies for similar blood and kidney diseases.
Who could benefit from this research
Good fit: Ideal candidates would be people with congenital dyserythropoietic anemia caused by a confirmed single (monoallelic) missense mutation in the KLF1 gene.
Not a fit: People whose anemia stems from non-KLF1 causes, different genetic mechanisms, or non-genetic conditions are unlikely to benefit from this specific approach.
Why it matters
Potential benefit: If successful, this approach could restore normal blood-cell production and reduce anemia by removing the harmful mutant protein while preserving the healthy protein.
How similar studies have performed: Protein-degrader technologies (for example PROTACs) have worked for some targets, but selectively degrading only the mutant allele is a novel and largely unproven strategy.
Where this research is happening
New York, United States
- Icahn School of Medicine at Mount Sinai — New York, United States (Active)
Researchers
- Principal investigator: Bieker, James J — Icahn School of Medicine at Mount Sinai
- Study coordinator: Bieker, James J
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.