Targeting a liver enzyme (NNMT) to treat alcohol-related liver damage
Official title: Hepatic Nicotinamide N-Methyltransferase (NNMT) as a Pathogenetic Mechanism and Therapeutic Target for Alcoholic Liver Disease
Funded at University of Illinois at Chicago · NIH-11098669 · Data updated 2026-11-12
Seeing if blocking a liver enzyme called NNMT can prevent or reduce alcohol-related liver damage for people with alcoholic liver disease.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Illinois at Chicago NIH-funded |
| Lab location | 1 site (Chicago, UNITED STATES) |
| Project start | August 15, 2022 |
| Project end | May 31, 2027 |
| Funding year | 2025 |
| Award (this year) | $387,826 |
| NIH project number | 5R01AA030255-04 |
| Project ID | NIH-11098669 on NIH RePORTER |
Who could benefit from this research
✓Could help
Adults with alcohol-related fatty liver or early alcoholic steatohepatitis would be the most likely future candidates for therapies coming from this work.
✕Less likely to help
People with advanced cirrhosis or end-stage liver failure are unlikely to benefit from early-stage metabolic interventions targeting NNMT.
What this research studies
Researchers are studying how a liver enzyme called NNMT changes key cellular nutrients (like NAD+ and SAM) and contributes to fatty liver and inflammation from chronic alcohol use. In lab models and mice they lower NNMT using genetic tools and examine effects on mitochondrial stress responses, PPAR-gamma activity, and liver fat accumulation, and they are probing how alcohol-driven signals (like ATF4) raise NNMT. The team will use these mechanistic findings to determine whether NNMT inhibition could be a promising pathway for therapy. Results would guide whether drug development or future human trials targeting NNMT are warranted.
Why it matters
Potential benefit: If successful, this work could point to new treatments that prevent or reverse early alcohol-related liver damage and reduce progression to cirrhosis.
How similar studies have gone: Early animal studies, including the investigators' own mouse experiments using NNMT knockdown, showed protective effects, but NNMT-targeting treatments remain largely untested in people.
Where this research is happening
-
University of Illinois at Chicago
Chicago, United States Active
Researchers
- Principal investigator: Song, Zhenyuan — University of Illinois at Chicago
- Study coordinator: Song, Zhenyuan
Related research
Other NIH-funded projects on the same topics.
-
Microbiome and Innate Immune Response in Alcohol-Related Liver Disease
Researchers are studying how gut bacteria and the body's first-line immune defenses contribute to liver damage from alcohol, with a focus on how a specific bacteria and its toxins affect disease severity.
-
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.