What causes liver scarring (fibrosis)
Official title: Pathobiology of liver fibrosis
Funded at Mayo Clinic Rochester · NIH-11325746 · Data updated 2026-11-12
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
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Mayo Clinic Rochester NIH-funded |
| Lab location | 1 site (Rochester, United States) |
| Project start | July 1, 2023 |
| Project end | April 30, 2028 |
| Funding year | 2026 |
| Award (this year) | $355,080 |
| NIH project number | 5R01DK136511-04 |
| Project ID | NIH-11325746 on NIH RePORTER |
Who could benefit from this research
✓Could help
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.
✕Less likely to help
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.
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.
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 gone: 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
-
Mayo Clinic Rochester
Rochester, United States Active
Researchers
- Principal investigator: Kostallari, Enis — Mayo Clinic Rochester
- Study coordinator: Kostallari, Enis
Related research
Other NIH-funded projects on the same topics.
-
Role of SMAD1/5/8 signaling in liver fibrosis
This grant explores how specific liver cell signals influence scarring (fibrosis) in the liver, with a focus on people who have alcohol-related liver disease or related conditions.
-
Targeting TGF-βRII to treat alcoholic liver fibrosis
A study to test a new peptide that blocks a key fibrosis signal and a gene-silencing approach to help reverse liver fibrosis caused by alcohol use.
-
Understanding how RNA binding proteins drive liver scarring and how to slow it down
A researcher team is studying how certain RNA binding proteins, especially LARP6, regulate the liver’s scar-building process in alcoholic liver disease to identify potential ways to reduce fibrosis.
-
S100A9+ immune cells driving liver scarring in MASLD/MASH
Affects people with MASLD/MASH may benefit from a better understanding of how certain immune cells contribute to liver fibrosis and how to stop it.
-
Liver fibrosis test platform using patient-derived liver tissue to speed anti-fibrosis drugs
A patient-focused liver fibrosis test platform is being developed to help speed the creation of medicines that treat liver scarring by using human-derived liver cells and tissue signals.
-
Role of HK2 in liver scarring, fatty liver disease, and liver cancer
A study in adults looks at how the enzyme HK2 helps drive liver scarring in NASH and may influence the development of liver cancer, with potential to point to new treatments.
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.