Clearing damaged mitochondria to stop harmful protein clumps in heart muscle cells
Mitophagy and Cardiac Myocyte Protein Aggregation
This project tests ways to help heart muscle cells remove damaged mitochondria and protein clumps for people with a genetic form of heart failure tied to the R120G HSPB5 mutation.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Washington University NIH-funded |
| Lab location | 1 site (Saint Louis, United States) |
| Project ID | NIH-11235179 on NIH RePORTER |
What this research studies
Researchers are working to understand why heart muscle cells with a faulty chaperone protein (R120G HSPB5) build up harmful protein clumps and damaged mitochondria. They use mouse models that carry the human mutation, examine mitochondrial accumulation of the mutant protein, measure markers of protein aggregation (like ubiquitin and p62), and study the role of the immune-related protein TRAF2 in mitophagy. The team compares what happens when TRAF2 is removed from heart cells versus when mitophagy is preserved, aiming to identify steps that reduce cell death and preserve heart function. Findings will guide development of treatments that boost the cell's ability to clear bad proteins and damaged mitochondria.
Who could benefit from this research
Good fit: Adults who have or are at risk for inherited proteotoxic cardiomyopathy, particularly those with the CRYAB (HSPB5) R120G mutation and related protein-aggregation heart disease, would be most relevant.
Not a fit: People whose heart failure is caused primarily by ischemic disease, hypertension, or other non-proteotoxic mechanisms are less likely to benefit directly from these findings.
Why it matters
Potential benefit: If successful, this work could point to new treatments that reduce protein aggregation and protect heart function in people with proteotoxic, inherited cardiomyopathy.
How similar studies have performed: Prior animal studies that boosted general autophagy showed some reduction in protein aggregates, but specifically targeting mitophagy and TRAF2 is a newer and less clinically tested approach.
Where this research is happening
Saint Louis, United States
- Washington University — Saint Louis, United States (Active)
Researchers
- Principal investigator: Diwan, Abhinav — Washington University
- Study coordinator: Diwan, Abhinav
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.