How the cell's protein cleanup system affects inflammation
Regulation of inflammation by the ubiquitin proteasome pathway
Looking at how changes in the cell's protein-tagging and cleanup system cause inflammation in people with VEXAS syndrome and similar blood-related inflammatory conditions.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | New York University School of Medicine NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11249533 on NIH RePORTER |
What this research studies
This work uses cells taken from people with VEXAS syndrome alongside laboratory cell models to study how somatic UBA1 mutations reduce protein ubiquitylation and overload the cell's protein-degradation machinery. Researchers focus on myeloid-lineage cells where the mutations accumulate and will measure inflammatory signaling and the unfolded protein response. The project examines the role of the ubiquitin–proteasome pathway, including the 20S proteasome, in driving disease-related inflammation. The goal is to pinpoint molecular steps that could become targets for future therapies.
Who could benefit from this research
Good fit: People diagnosed with VEXAS syndrome or with unexplained, treatment‑resistant inflammatory/hematologic conditions—especially those known to carry UBA1 mutations—would be the most relevant candidates.
Not a fit: People without UBA1 mutations or whose conditions are unrelated to ubiquitin–proteasome dysfunction, and anyone seeking an immediate therapeutic intervention, are unlikely to directly benefit from this mechanistic research.
Why it matters
Potential benefit: If successful, this research could identify biological targets that lead to new treatments for VEXAS syndrome and other treatment-resistant inflammatory blood disorders.
How similar studies have performed: Prior studies have identified UBA1 mutations as the cause of VEXAS and shown inflammatory pathway activation in patient cells, but targeted treatments based on these findings have not yet been proven.
Where this research is happening
New York, United States
- New York University School of Medicine — New York, United States (Active)
Researchers
- Principal investigator: Beck, David — New York University School of Medicine
- Study coordinator: Beck, David
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.