Why some colon cancers switch back to immature (fetal-like) cell states
Molecular mechanisms of developmental reprogramming in colorectal cancer
This project looks at whether a protein called SOX9 drives colorectal tumors to turn on fetal-like genes and whether changing that activity could make tumor cells behave more like normal intestine cells for people with colorectal cancer.
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-11134749 on NIH RePORTER |
What this research studies
From a patient's perspective, researchers will study tumor behavior using mouse models and organoids grown from patient tumor samples to understand how cancer cells turn on fetal-like genetic programs. They will use single-cell RNA sequencing and ATAC-seq to map which genes are active and which regions of DNA are open in individual tumor cells, and apply computational topic modeling to nominate key regulators. The team will use CRISPR gene editing and transcription-factor binding studies to test whether SOX9 directly opens chromatin and reactivates fetal genes. The overall goal is to find molecular switches that could be targeted to promote tumor cell differentiation and curb tumor growth.
Who could benefit from this research
Good fit: Ideal candidates would be people with colorectal cancer who can donate tumor tissue or whose tumors are cultured as patient-derived organoids, typically through Dana-Farber or collaborating centers.
Not a fit: Patients without colorectal cancer, or those whose tumors do not show SOX9-driven fetal gene activation or who need immediate standard-of-care treatment, are unlikely to receive direct benefit from this lab-focused research.
Why it matters
Potential benefit: If successful, this work could identify new molecular targets that lead to therapies that push colorectal tumor cells to mature and stop growing, potentially reducing tumor burden.
How similar studies have performed: Early laboratory studies, including work from this team, showed that blocking SOX9 induced differentiation and reduced tumor burden in model systems, but this approach has not yet been proven in patients.
Where this research is happening
Boston, United States
- Dana-Farber Cancer Inst — Boston, United States (Active)
Researchers
- Principal investigator: Sethi, Nilay — Dana-Farber Cancer Inst
- Study coordinator: Sethi, Nilay
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.