What causes liver scarring (fibrosis)
Pathobiology of liver fibrosis
['FUNDING_R01'] · MAYO CLINIC ROCHESTER · NIH-11325746
The team is testing whether increased sugar-burning inside liver support cells makes them send out tiny protein-packed vesicles that worsen scarring, with the goal of helping people with liver fibrosis.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | MAYO CLINIC ROCHESTER (nih funded) |
| Locations | 1 site (ROCHESTER, UNITED STATES) |
| Trial ID | NIH-11325746 on ClinicalTrials.gov |
What this research studies
From a patient's point of view, researchers are studying hepatic stellate cells — the liver support cells that drive scarring — to see how a growth signal (PDGF) boosts their sugar metabolism and causes them to release tiny vesicles loaded with scar-promoting proteins. They will use human stellate cells in the lab and animal models to trace how increased glycolysis changes gene activity via a histone mark (H3K9ac) and upregulates RAB genes that control vesicle trafficking. The team will apply genetic tools to turn off specific genes in stellate cells and use mice lacking a key glycolysis enzyme (HK2) in those cells to test whether blocking this pathway reduces fibrosis. The overall aim is to identify steps that could become targets for new treatments to slow or stop liver scarring.
Who could benefit from this research
Good fit: Ideal participants would be adults with chronic liver disease and evidence of liver fibrosis who might donate tissue or later qualify for trials testing therapies based on these findings.
Not a fit: People without liver disease, or those with immediate end-stage liver failure who need urgent transplant, are unlikely to benefit directly from this basic and preclinical work.
Why it matters
Potential benefit: If successful, this work could point to new drug targets that slow or reverse liver fibrosis and reduce the need for liver transplant.
How similar studies have performed: Some prior animal studies suggest blocking glycolysis in stellate cells can reduce scarring, but linking glycolysis to vesicle release via H3K9 acetylation and RAB gene activation is a newer approach.
Where this research is happening
ROCHESTER, UNITED STATES
- MAYO CLINIC ROCHESTER — ROCHESTER, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: KOSTALLARI, ENIS — MAYO CLINIC ROCHESTER
- Study coordinator: KOSTALLARI, ENIS
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.