Chip phosphorylation boosts breakdown of mutant TTR to help heart amyloidosis
Official title: Chip phosphorylation stimulates the degradation of mutant transthyretin to attenuate cardiac amyloidosis
Funded at Johns Hopkins University · NIH-11386483 · Data updated 2026-11-12
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.
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 | 2026 |
| Award (this year) | $674,753 |
| NIH project number | 5R01HL169273-03 |
| Project ID | NIH-11386483 on NIH RePORTER |
Who could benefit from this research
✓Could help
Patients with transthyretin-related cardiomyopathy (ATTR-CM) or those contributing tissue samples for biorepository studies and iPSC-derived heart models.
✕Less likely to help
Individuals without ATTR-CM or without access to related tissue samples/biorepository studies may not benefit directly.
What this research studies
Researchers are studying how activating a molecule called protein kinase G (PKG) can promote the breakdown of misfolded transthyretin in the heart using the proteasome and lysosome pathways. They have developed new lab models, including engineered heart tissue and cardiac organoids from patient-derived cells, to better mimic ATTR-CM in the lab. The work also includes creating a biorepository of patient heart tissue to understand disease mechanisms and test potential therapies. The goal is to identify strategies that could reduce TTR deposits and improve heart function in people with ATTR-CM.
Why it matters
Potential benefit: If successful, the findings could lead to therapies that reduce heart damage in ATTR-CM by enhancing the body’s protein-cleanup systems.
How similar studies have gone: Preclinical models and patient-derived systems have shown that modulating protein degradation can affect cardiac disease in vitro, with ongoing work translating to animal and human studies.
Where this research is happening
-
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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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.
-
Improving outcomes in cardiac amyloidosis using innovative imaging techniques
This study is looking at new ways to use advanced imaging to improve how we diagnose and treat cardiac amyloidosis, helping doctors create personalized care plans for patients while also training future researchers in this important area.
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.