Inside our heart cells are tiny, tube-like structures called microtubules that act as scaffolds, helping the cells maintain their shape and function. When microtubules become too stiff due to a chemical change called detyrosination, the heart muscle struggles to contract and relax. Such changes contribute to heart disease, including heart failure, one of the leading causes of death worldwide, for which effective targeted treatments are still lacking.
Impact
Our research uses stem cell-derived heart cells to model patient-specific disease processes in vitro. By investigating microtubule detyrosination in these “hearts in a dish,” we will uncover how stiffened microtubules impair cardiac function and identify new therapeutic targets, advancing our understanding and contributing to the urgent need for effective treatments against heart failure.
reNEW research
We have successfully generated patient-specific heart cells from human stem cell lines carrying mutations that cause inherited cardiomyopathies and heart failure. Using this model, we are currently investigating how microtubule stiffening through detyrosination drives disease progression and we are currently testing small molecules to counteract this process as potential new therapies.
Image description
Detyrosinated microtubules (green) and nuclei (blue) of stem cell-derived heart cells carrying a mutation leading to dilated cardiomyopathy, one of the most common causes of heart failure.
Credits
Viviana Meraviglia, Senior researcher, Bellin & Mummery lab, reNEW Leiden.
