Understanding how the unfolded protein response affects liver disease
Official title: Dysregulation of the unfolded protein response in the pathogenesis of non-alcoholic steatohepatitis
Funded at Massachusetts General Hospital · NIH-11054379 · Data updated 2026-11-12
This study is looking at how a protective process in the liver, called the unfolded protein response, is lost in people with non-alcoholic steatohepatitis (NASH), and it aims to find ways to help restore this process to prevent liver damage.
Quick facts
| Grant type | Career grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Massachusetts General Hospital NIH-funded |
| Lab location | 1 site (Boston, United States) |
| Project start | January 9, 2025 |
| Project end | November 30, 2029 |
| Funding year | 2025 |
| Award (this year) | $172,060 |
| NIH project number | 1K08DK139370-01A1 |
| Project ID | NIH-11054379 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates for this research are individuals over 21 years old who are diagnosed with non-alcoholic steatohepatitis.
✕Less likely to help
Patients with other forms of liver disease, such as alcoholic liver disease or viral hepatitis, may not benefit from this research.
What this research studies
This research investigates the loss of a protective mechanism in the liver known as the unfolded protein response (UPR) in patients with non-alcoholic steatohepatitis (NASH). By using advanced techniques like single-cell RNA sequencing and precision cut liver slices, the researchers aim to uncover the mechanisms behind UPR loss and its role in the development of NASH. The study will involve both mouse models and human liver specimens to explore potential therapeutic targets that could restore UPR function and protect against liver damage.
Why it matters
Potential benefit: If successful, this research could lead to new therapeutic strategies for treating non-alcoholic steatohepatitis, potentially improving liver health and reducing the need for liver transplants.
How similar studies have gone: Other research has shown promising results in understanding the unfolded protein response in various diseases, suggesting that this approach could yield valuable insights for NASH as well.
Where this research is happening
-
Massachusetts General Hospital
Boston, United States Active
Researchers
- Principal investigator: Sherman, Marc S — Massachusetts General Hospital
- Study coordinator: Sherman, Marc S
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.
-
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.
-
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.
-
New small-molecule medicines that stabilize Axin to treat non-alcoholic steatohepatitis (NASH)
Trying new small-molecule drugs that stabilize Axin to lower liver fat and scarring for people with NASH.
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.