How metabolic stress causes mitochondrial damage that can lead to fatty liver–related liver cancer
Project 3: Metabolic stress induces mitochondrial dysfunction through STARD1 and SAB leading to HCC
This project looks at whether changes in two mitochondrial proteins caused by overnutrition and type 2 diabetes push fatty liver disease toward liver cancer, especially for people with obesity or diabetes.
Quick facts
| Grant type | P01 program project |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Sanford Burnham Prebys Medical Discovery Institute NIH-funded |
| Lab location | 1 site (La Jolla, United States) |
| Project ID | NIH-11189766 on NIH RePORTER |
What this research studies
Researchers will study two mitochondrial proteins, STARD1 and SAB, that rise with endoplasmic reticulum stress in fatty liver disease. They will use human liver samples, patient-derived tumor models, and laboratory models to see how these proteins change cholesterol and bile acid handling and harm mitochondria. The team will test what happens when these proteins or related signaling pathways (such as JNK, ATF6, and NRF2/FBP1) are turned off or altered. The goal is to link these molecular changes to the progression from NASH (fatty liver with inflammation) to hepatocellular carcinoma.
Who could benefit from this research
Good fit: Adults with nonalcoholic fatty liver disease or NASH, particularly those with obesity or type 2 diabetes, would be the most relevant group for related clinical studies or future trials.
Not a fit: People without fatty liver disease or those whose liver cancer is caused by viral hepatitis or unrelated genetic disorders are unlikely to benefit directly from this specific line of research.
Why it matters
Potential benefit: If successful, this work could point to new targets for preventing or treating NASH-related liver cancer and help identify patients at higher risk.
How similar studies have performed: Previous studies have linked ER stress and mitochondrial dysfunction to NASH and liver cancer, but directly targeting STARD1 and SAB for this purpose is a newer approach still in early research stages.
Where this research is happening
La Jolla, United States
- Sanford Burnham Prebys Medical Discovery Institute — La Jolla, United States (Active)
Researchers
- Principal investigator: Kaplowitz, Neil — Sanford Burnham Prebys Medical Discovery Institute
- Study coordinator: Kaplowitz, Neil
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.