New small-molecule medicines that stabilize Axin to treat non-alcoholic steatohepatitis (NASH)
Official title: Axin Stabilization by Novel Small Molecules to Treat Non-alcoholic Steatohepatitis
Funded at University of Maryland Baltimore · NIH-11261165 · Data updated 2026-11-12
Trying new small-molecule drugs that stabilize Axin to lower liver fat and scarring for people with NASH.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Maryland Baltimore NIH-funded |
| Lab location | 1 site (Baltimore, United States) |
| Project start | April 1, 2023 |
| Project end | January 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $538,952 |
| NIH project number | 5R01DK133421-04 |
| Project ID | NIH-11261165 on NIH RePORTER |
Who could benefit from this research
✓Could help
Adults diagnosed with non-alcoholic steatohepatitis (NASH), often with obesity, diabetes, or metabolic syndrome, would be the most relevant group.
✕Less likely to help
People without NASH or whose liver disease is caused by alcohol, viral hepatitis, or unrelated conditions are unlikely to benefit from these compounds.
What this research studies
This research is developing drug-like compounds (lead examples YW1128 and YA6060) that target liver pathways tied to metabolism and scarring. The compounds stabilize a protein called Axin, which both reduces Wnt/beta-catenin signaling and activates AMPK, pathways linked to fatty liver and fibrosis. In lab tests and mouse models the leads reduced liver fat and fibrosis, and the team is studying how they bind a protein called TAB182 to improve activity and drug-like properties. The goal is to optimize these molecules and generate data needed to move toward human testing.
Why it matters
Potential benefit: If successful, this work could lead to the first drug treatments that reduce liver fat and fibrosis in people with NASH.
How similar studies have gone: AMPK activators and Wnt pathway modulators have shown promise in laboratory and early clinical research, but no approved NASH drugs exist yet, so this dual-action approach is promising but not proven in patients.
Where this research is happening
-
University of Maryland Baltimore
Baltimore, United States Active
Researchers
- Principal investigator: Shu, Yan — University of Maryland Baltimore
- Study coordinator: Shu, Yan
Related research
Other NIH-funded projects on the same topics.
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Role of metabolic stress in NASH-related liver cancer
This grant explores how metabolic stress linked to NASH may drive liver cancer and looks for ways to interrupt that process to help patients.
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TREM2: a helper in liver inflammation and scarring in NASH
A new approach studies how a liver immune receptor called TREM2 helps protect against liver inflammation and scarring in people with fatty liver disease that can progress to NASH.
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Genes behind fatty liver disease and NASH
This project looks at how specific genes change fatty liver disease and scarring to help guide better tests and treatments for people with NAFLD/NASH.
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Ex-vivo bioengineered liver cells to study NASH-related dysfunction
Researchers will use patient-derived stem cell–made liver cells in a lab setup to understand why NASH causes liver damage and how stiffness of the liver’s surroundings affects this process.
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How TREM2 on immune cells affects fatty liver disease (NASH)
This project looks at whether the immune protein TREM2 helps drive liver inflammation and scarring in people with NASH.
-
How bile acids and sphingosine-1-phosphate affect fatty liver (NASH)
This project looks at how bile acids and a fat-signaling molecule called sphingosine-1-phosphate change liver cells in people with NASH to find new treatment leads.
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.