Targeting a protein switch that controls p53 and PD‑L1 in cancer
Co-regulation of p53 and PD-L1 by the VPRBP-USP2 axis in transcription and ubiquitylation
This project is testing whether blocking the VPRBP–USP2 pathway can boost the cancer‑blocking protein p53 and lower PD‑L1 on tumor cells to help people whose tumors keep a normal p53.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Columbia University Health Sciences NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11285231 on NIH RePORTER |
What this research studies
The team is working in the lab to understand how two proteins, VPRBP and USP2, control the tumor suppressor p53 and the immune‑shielding protein PD‑L1. They will use cell models and animal models to see how changing this pathway affects cancer cell survival and PD‑L1 levels. The researchers aim to find ways to stabilize p53 while also reducing PD‑L1 to make tumors more visible to the immune system. Results could point to new drug strategies or combinations with existing PD‑1/PD‑L1 immunotherapies.
Who could benefit from this research
Good fit: People with tumors that retain a normal (wild‑type) p53, especially cancers that show higher PD‑L1 on tumor cells, would be the most likely candidates for future therapies based on this work.
Not a fit: Patients whose tumors have mutated p53 or whose cancers are driven by unrelated pathways are less likely to benefit from treatments targeting this axis.
Why it matters
Potential benefit: If successful, this work could lead to safer methods to reactivate p53 and improve responses to PD‑1/PD‑L1 immunotherapy for some cancer patients.
How similar studies have performed: Previous approaches that reactivate p53, such as Mdm2 inhibitors, showed promise but faced toxicity issues, and PD‑1/PD‑L1 antibodies have helped patients with PD‑L1 positive tumors, while targeting VPRBP–USP2 is a newer and largely untested strategy.
Where this research is happening
New York, United States
- Columbia University Health Sciences — New York, United States (Active)
Researchers
- Principal investigator: Gu, Wei — Columbia University Health Sciences
- Study coordinator: Gu, Wei
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.