Boosting CHIP to help clear mutant transthyretin from the heart
Official title: Chip phosphorylation stimulates the degradation of mutant transthyretin to attenuate cardiac amyloidosis
Funded at Johns Hopkins University · NIH-11082288 · Data updated 2026-11-12
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 start | September 1, 2024 |
| Project end | July 31, 2028 |
| Funding year | 2025 |
| Award (this year) | $685,249 |
| NIH project number | 5R01HL169273-02 |
| Project ID | NIH-11082288 on NIH RePORTER |
Who could benefit from this research
✓Could help
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.
✕Less likely to help
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.
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.
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 gone: 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
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Johns Hopkins University
Baltimore, United States Active
Researchers
- Principal investigator: Ranek, Mark John — Johns Hopkins University
- Study coordinator: Ranek, Mark John
Related research
Other NIH-funded projects on the same topics.
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Identifying Hidden Cardiac Amyloidosis in Black V122I TTR Carriers
This project looks for early signs of heart damage in Black individuals who carry the V122I TTR variant and may benefit from new treatments if caught early.
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Chip phosphorylation boosts breakdown of mutant TTR to help heart amyloidosis
A scientist-led project aims to help people with a heart disease caused by a mutant protein called transthyretin (TTR) by boosting the body’s protein-cleanup systems to remove the harmful TTR deposits.
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Finding transthyretin heart amyloid from lumbar spine surgery tissue
This project looks for transthyretin (TTR) amyloid in tissue removed during lumbar spine surgery to find people who may later develop TTR cardiac amyloidosis.
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Blood biomarker test for heart amyloidosis in Black and Hispanic people
A blood test called TAD1 is being checked to detect dangerous heart amyloidosis earlier in Black and Hispanic patients who have heart failure.
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PET tracer to image cardiac amyloidosis
A new PET tracer is being developed to help visualize amyloid buildup in the heart, potentially helping people with amyloidosis and related heart disease.
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Why losing parts of the Y chromosome may drive TTR heart amyloidosis in men
The team is looking at whether loss of the Y chromosome in blood cells helps explain why men develop transthyretin (TTR) heart amyloidosis.
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.