How thalidomide-like drugs make cells destroy specific proteins
The molecular basis of IMiD induced neo-substrate recruitment to the CRL4CRBN ubiquitin E3 ligase
This project looks at how thalidomide and related drugs cause cells to tag and break down certain proteins, to better understand why they can cause birth defects and affect patients using these medicines.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Dana-Farber Cancer Inst NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project ID | NIH-11306651 on NIH RePORTER |
What this research studies
Researchers are using lab experiments and an engineered mouse model to see how thalidomide-like drugs cause the cellular protein-removal machinery (CRL4CRBN) to target new proteins such as SALL4 during embryo development. They will measure gene and protein levels and track developmental changes in embryos after exposure to IMiD drugs. Molecular assays will map how these drugs bind the E3 ligase complex and redirect it to different substrates. The team aims to connect these molecular events to the birth defects observed in humans.
Who could benefit from this research
Good fit: People or families affected by thalidomide-related birth defects, acrorenoocular syndrome, or Del(5q) MDS could be relevant for future sample donation or follow-up studies.
Not a fit: This basic science project is not designed to provide immediate new treatments for individuals currently receiving IMiD therapies.
Why it matters
Potential benefit: If successful, this work could explain how IMiD drugs cause birth defects and help guide safer drug design and clinical monitoring.
How similar studies have performed: Prior studies have shown IMiDs can redirect CRL4CRBN to target proteins like IKZF1/3 and SALL4, but the detailed molecular steps linking this to teratogenicity remain incompletely understood.
Where this research is happening
Boston, United States
- Dana-Farber Cancer Inst — Boston, United States (Active)
Researchers
- Principal investigator: Fischer, Eric Sebastian — Dana-Farber Cancer Inst
- Study coordinator: Fischer, Eric Sebastian
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.