How defects at heart-cell junctions affect the cell's nucleus in arrhythmogenic right ventricular cardiomyopathy
Intercalated disc-nuclear lamina coupling as a molecular substrate for arrhythmogenic cardiomyopathy
Researchers want to understand whether changes in a heart cell protein called plakophilin‑2 cause internal cell damage that leads to dangerous heart rhythms in people with arrhythmogenic right ventricular cardiomyopathy.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Rochester NIH-funded |
| Lab location | 1 site (Rochester, United States) |
| Project ID | NIH-11138622 on NIH RePORTER |
What this research studies
This work looks inside heart muscle cells to see how mutations in the protein plakophilin‑2 (PKP2) change the nuclear envelope and lead to DNA damage that may promote ARVC. The team will use mouse models, experiments in lab-grown heart cells, and samples from ARVC patients to track structural links from the cell surface to the nucleus. They will measure DNA damage responses, changes in gene activity, and how intermediate filaments like desmin connect to the desmosome and nuclear lamina. The goal is to connect molecular changes to the structural and rhythm problems seen in ARVC.
Who could benefit from this research
Good fit: People diagnosed with arrhythmogenic right ventricular cardiomyopathy or who carry disease-relevant PKP2 mutations, especially those able to provide clinical data or tissue samples, would be most relevant to this work.
Not a fit: Patients with unrelated forms of heart disease or arrhythmias not linked to PKP2 or ARVC are unlikely to directly benefit from this specific molecular research.
Why it matters
Potential benefit: If successful, this work could identify molecular steps that cause cell damage and point to targets for therapies to prevent dangerous arrhythmias in people with ARVC.
How similar studies have performed: Previous studies in mouse models and human tissue have shown PKP2 mutations can disrupt the nuclear envelope and cause DNA damage, but translating those findings into treatments remains largely untested.
Where this research is happening
Rochester, United States
- University of Rochester — Rochester, United States (Active)
Researchers
- Principal investigator: Small, Eric M — University of Rochester
- Study coordinator: Small, Eric M
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.