Turning on fetal hemoglobin by degrading the BCL11A protein
DEGRADATION OF BCL11A PROTEIN FOR HbF REACTIVATION
Using small-molecule drugs to lower BCL11A and switch fetal hemoglobin back on for adults with beta‑thalassemia or sickle cell disease.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Boston Children's Hospital NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project ID | NIH-11167799 on NIH RePORTER |
What this research studies
Researchers will develop small drug molecules that cause the BCL11A protein to be broken down in red blood cell precursors. They will use lab-grown human erythroid cells and CD34-derived cells to see when fetal (γ) globin is switched on during different cell-cycle stages. The team will measure newly made globin RNA and protein after acute targeted protein degradation to map timing and strength of reactivation. Findings will guide selection and optimization of drug candidates that could later be tested in people.
Who could benefit from this research
Good fit: Adults with sickle cell disease or beta‑thalassemia who are interested in non‑transplant, drug-based therapies would be the likely candidates for future clinical testing stemming from this work.
Not a fit: Children, people without hemoglobin disorders, or patients needing immediate transplant-based care are unlikely to benefit directly from this research.
Why it matters
Potential benefit: Could lead to an easier, drug-based treatment that raises fetal hemoglobin and reduces complications for people with sickle cell disease or beta-thalassemia.
How similar studies have performed: Gene‑editing and gene‑therapy approaches that reduce BCL11A have already raised fetal hemoglobin in patients, but small‑molecule targeted protein degradation is a newer, less tested approach.
Where this research is happening
Boston, United States
- Boston Children's Hospital — Boston, United States (Active)
Researchers
- Principal investigator: Orkin, Stuart H — Boston Children's Hospital
- Study coordinator: Orkin, Stuart 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.