How cohesin mutations change RNA splicing in myelodysplastic syndrome
Molecular mechanisms of splicing dependency in cohesin-mutant myelodysplasia
This project looks at how mutations in the cohesin complex make myelodysplastic syndrome (MDS) cells depend on RNA splicing, to guide new treatment strategies.
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-11233294 on NIH RePORTER |
What this research studies
The team uses new genetically engineered models of MDS that carry cohesin mutations to study how the cohesin complex interacts with the cell's splicing machinery. They will map RNA–protein interactions and compare cells with and without common mutations such as STAG2 or SF3B1. Laboratory experiments will test how disrupting splicing affects survival of cohesin-mutant cells and will probe candidate drugs that target the spliceosome or related pathways. The work aims to trace the steps from mutation to faulty splicing and highlight pathways that could be targeted in patients.
Who could benefit from this research
Good fit: People with myelodysplastic syndromes, especially those whose disease carries cohesin mutations (for example STAG2) or splicing-factor mutations, would be most relevant.
Not a fit: Patients without MDS or without cohesin-related mutations are unlikely to gain direct benefit from this project in the short term.
Why it matters
Potential benefit: If successful, this work could identify new drug targets for patients with cohesin-mutant MDS and inform future clinical trials.
How similar studies have performed: Previous laboratory studies have linked cohesin proteins to splicing factors and shown splicing-related vulnerabilities in blood cancers, but the specific RNA-mediated mechanism and therapeutic targeting here is relatively new.
Where this research is happening
Boston, United States
- Dana-Farber Cancer Inst — Boston, United States (Active)
Researchers
- Principal investigator: Tothova, Zuzana — Dana-Farber Cancer Inst
- Study coordinator: Tothova, Zuzana
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.