Boosting CHIP to help clear mutant transthyretin from the heart
Chip phosphorylation stimulates the degradation of mutant transthyretin to attenuate cardiac amyloidosis
Sees if turning on CHIP and a partner enzyme (PKG) helps heart cells and lab-grown heart tissue clear mutant transthyretin for people with transthyretin cardiac amyloidosis.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Johns Hopkins University NIH-funded |
| Lab location | 1 site (Baltimore, United States) |
| Project ID | NIH-11082288 on NIH RePORTER |
What this research studies
If I had transthyretin cardiac amyloidosis (ATTR-CM), this work would sound like researchers trying to restore a natural protein‑cleanup system in heart cells. They use heart biopsy samples from patients and lab-grown human heart tissues made from stem cells to model how the mutant transthyretin damages the heart. The team measures PKG activity and phosphorylation of CHIP, and tests whether boosting those pathways helps cells break down and remove the bad protein. They have also built a biorepository of patient biopsies to guide and validate their findings in human tissue.
Who could benefit from this research
Good fit: Adults diagnosed with transthyretin cardiac amyloidosis (ATTR-CM), especially those with known TTR mutations like V122I or who are willing to provide biopsy samples or join a tissue donation program, are the most relevant candidates.
Not a fit: People with non‑TTR forms of amyloidosis (for example AL amyloidosis), other unrelated heart diseases, or those unwilling to provide samples are unlikely to receive direct benefit from this work.
Why it matters
Potential benefit: If successful, this could lead to treatments that help the heart remove harmful mutant transthyretin and reduce heart damage from ATTR-CM.
How similar studies have performed: Related lab research has shown PKG can boost protein degradation and the investigators have pilot data showing reduced PKG/CHIP activity in ATTR-CM patients, but translating these findings into clinical treatments remains experimental.
Where this research is happening
Baltimore, United States
- Johns Hopkins University — Baltimore, United States (Active)
Researchers
- Principal investigator: Ranek, Mark John — Johns Hopkins University
- Study coordinator: Ranek, Mark John
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.