How thyroid hormone receptors and their helper proteins affect liver metabolism and fatty liver (NASH)
Integrative Physiology of Thyroid Hormone Receptors and Nuclear Receptor Corepressors
This work looks at how thyroid hormone receptors and their partner proteins control metabolism and could help people with fatty liver disease (NASH).
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Pennsylvania NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project ID | NIH-11330513 on NIH RePORTER |
What this research studies
You would hear that researchers are studying how thyroid hormones switch genes on and off in the liver by using proteins called TRβ, NCOR1/2, and HDAC3. They combine genetically tagged mice with genomic tools like ATAC-seq, proximity labeling, and CRISPR approaches to map where these proteins act and how gene regulation changes in fatty liver disease. They also trace tryptophan metabolism and production of anti-inflammatory kynurenine metabolites using metabolic flux analysis. The team aims to explain why liver genes are misregulated in NASH and how TRβ-targeting drugs improve fat, inflammation, and scarring.
Who could benefit from this research
Good fit: People with non-alcoholic fatty liver disease or biopsy-proven NASH, and possibly those with metabolic or thyroid-related conditions, would be the most relevant candidates for participation or future trials.
Not a fit: People without fatty liver disease or unrelated medical conditions are unlikely to receive direct benefit from this work in the near term.
Why it matters
Potential benefit: Could point to better-targeted thyroid receptor drugs or metabolic therapies that reduce liver fat, inflammation, and fibrosis in people with NASH.
How similar studies have performed: Several TRβ-selective drugs have shown promise in clinical trials for reducing liver fat, but the detailed gene-level and metabolic mechanisms targeted here remain relatively novel.
Where this research is happening
Philadelphia, United States
- University of Pennsylvania — Philadelphia, United States (Active)
Researchers
- Principal investigator: Lazar, Mitchell a. — University of Pennsylvania
- Study coordinator: Lazar, Mitchell a.
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.