Thesis defense Sebastiaan van Kampen: Uncovering the molecular mechanisms underlying arrhythmogenic cardiomyopathy using the CRISPR-toolbox

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Sebastiaan van Kampen successfully defended his thesis “Uncovering the molecular mechanisms underlying arrhythmogenic cardiomyopathy using the CRISPR-toolbox” on May 9. During his PhD in the lab of Eva van Rooij, he managed to unravel some secrets about the heart disease arrhythmogenic cardiomyopathy. He used a combination of cells, mouse models and heart muscle tissue and identified new mechanisms that underlie the disease. The results of this research may contribute to the development of effective medicines for patients.

Arrhythmogenic cardiomyopathy (ACM) is a progressive and often hereditary disease which is characterized by electrical and structural changes in the ventricles of the heart. Since the underlying mechanisms of the disease remain largely unknown, treatments are currently focused on controlling and fighting the symptoms of patients. A better understanding is thus crucial for the development of therapies that can cure the disease.

Burning bridges

To gain more insight into the disease, Van Kampen conducted a thorough investigation of complex protein structures in the heart called desmosomes. One could say that desmosomes form bridges between individual heart muscle cells. Without desmosomes the heart is unable to build enough force to exert its pumping function in the body: this is exactly what happens in ACM patients. Van Kampen used several model systems to find out how desmosomes are lowered in ACM patients. “Thanks to CRISPR technology, we were able to study the effect of frequently observed and newly identified mutations in ACM. In this way, we discovered that crucial components are actively broken down, resulting in a deteriorated pumping function,” explains Van Kampen.

A step forward

The results from this thesis co-occur with several other independent studies that have reached similar conclusions. The findings are thus robust. “It’s good to see that our findings are confirmed by others. This implies that breakdown of desmosomes could be an interesting target for future therapies and that those therapies could help many people,” says Van Kampen. Research in the coming years will have to show whether this is indeed the case.

Part of an exciting community

Van Kampen looks back fondly on his PhD at the Hubrecht Institute, although it was sometimes challenging to keep up-to-date with all literature and conduct research himself simultaneously. He enjoyed being part of the scientific community where innovations follow each other quickly. He concludes: “I had the freedom and time to develop myself as a scientist and as a person. I look forward to use all experiences in a new challenge!”.

Sebastiaan celebrated his defense with a beer. In the meantime, he has found his new challenge and started working as a postdoc in the lab of Valeria Orlova (LUMC). Here, he uses vessel-on-a-chip models to study the mechanisms that underlie vascular diseases.