Liver protein complex that drives inflammation and gut damage in alcohol-related liver disease
Official title: Pathogenic role of a protein complex of liver origin as regulator of a proinflammatory program that drives hepatic and intestinal injury in alcoholic liver disease
Funded at Jesse Brown VA Medical Center · NIH-11131054 · Data updated 2026-11-12
This project looks at how a protein released from the liver sparks inflammation that harms both the liver and the gut in people with alcohol-related liver disease.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Jesse Brown VA Medical Center NIH-funded |
| Lab location | 1 site (Chicago, United States) |
| Project start | July 1, 2021 |
| Project end | June 30, 2026 |
| Funding year | 2025 |
| NIH project number | 5I01BX005093-05 |
| Project ID | NIH-11131054 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal participants would be adults with alcohol-related liver disease, such as alcoholic hepatitis or evidence of alcohol-induced liver injury, and people willing to provide blood samples or clinical information.
✕Less likely to help
People without alcohol-related liver disease or whose liver problems are caused by unrelated conditions (for example, viral hepatitis alone or genetic liver disorders) are unlikely to benefit from this specific work.
What this research studies
If you have alcohol-related liver disease, researchers are tracking a liver protein called HMGB1 that becomes oxidized after alcohol damage and may trigger inflammation. They will use lab and animal models and analyze human blood samples to measure oxidized HMGB1 and immune responses. The team will test whether blocking oxidized HMGB1 or its receptor (RAGE) on immune cells reduces liver injury and prevents the gut barrier from becoming leaky. Findings aim to link liver signals to intestinal damage and point to ways to stop this harmful cycle.
Why it matters
Potential benefit: If successful, this work could lead to new treatments that lower liver inflammation and protect the gut in people with alcohol-related liver disease.
How similar studies have gone: Preclinical work, including the investigators' prior studies, showed that blocking oxidized HMGB1 or removing RAGE on immune cells reduced liver inflammation and gut dysfunction in animal models, but applying these findings in patients is still new.
Where this research is happening
-
Jesse Brown VA Medical Center
Chicago, United States Active
Researchers
- Principal investigator: Nieto, Natalia — Jesse Brown VA Medical Center
- Study coordinator: Nieto, Natalia
Related research
Other NIH-funded projects on the same topics.
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Microbiome and Innate Immune Response in Alcohol-Related Liver Disease
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-
Lipotoxicity and Alcohol-Related Liver Disease
This project studies how fatty acids cause liver cell damage in alcohol-related liver disease to help develop new treatments.
-
NNMT as a Target to Treat Alcoholic Liver Disease
A study to see if blocking an enzyme called NNMT can help people with alcoholic liver disease.
-
How gut fungi may drive alcohol-related liver damage
Researchers are looking at whether specific fungi in the gut make liver damage from heavy drinking worse in people with alcohol-related liver disease.
-
Heat shock protein 90 and alcohol-related liver disease: how macrophages fuel inflammation
This project looks at how a cellular stress protein, HSP90, affects liver inflammation in people with alcohol-related liver disease by focusing on macrophages.
-
Why alcohol-related liver disease can come back after a transplant
Looking at whether an enzyme called CerS6 helps fat build up in the liver and whether measuring CerS6 can help detect or predict return of alcohol-related liver disease before or after a liver transplant.
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.