How a common PNPLA3 gene change affects alcohol-related liver damage in lab-grown human liver tissue
Studying alcohol-associated liver disease and its interaction with rs738409 variant in PNPLA3 in a liver culture model
This project looks at how the PNPLA3 rs738409 gene change changes the way human liver cells respond to alcohol, aiming to help people with alcohol-associated liver disease.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Cleveland Clinic Lerner Com-Cwru NIH-funded |
| Lab location | 1 site (Cleveland, United States) |
| Project ID | NIH-11197607 on NIH RePORTER |
What this research studies
Researchers grow human-derived liver cells (hepatocytes, macrophages, and stellate cells) from induced pluripotent stem cells to recreate a working mini-liver. They expose this multicellular liver culture to alcohol levels similar to those seen in patients and compare responses between cells with and without the PNPLA3 rs738409 variant. The team measures cell injury, inflammation, and fibrotic responses to understand how the genetic variant alters disease processes. Findings will guide the search for drug targets and improve models that reflect human-specific disease biology.
Who could benefit from this research
Good fit: Adults with alcohol-associated liver disease, especially those known to carry the PNPLA3 rs738409 variant, are most relevant to the questions this work addresses.
Not a fit: People without alcohol-related liver disease or whose liver problems stem from unrelated causes are unlikely to directly benefit from these specific findings.
Why it matters
Potential benefit: If successful, this work could reveal why some people are more vulnerable to alcohol-related liver damage and point to new targets for future treatments or personalized approaches.
How similar studies have performed: Animal models and some human cell–based liver models have provided useful insights, but applying multicellular human iPSC liver cultures to study PNPLA3 in alcohol-related disease is relatively new.
Where this research is happening
Cleveland, United States
- Cleveland Clinic Lerner Com-Cwru — Cleveland, United States (Active)
Researchers
- Principal investigator: Wu, Xianfang — Cleveland Clinic Lerner Com-Cwru
- Study coordinator: Wu, Xianfang
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 below.