Cardiogenetics ()

Background

Cardiomyopathies are disorders of the heart muscle, resulting in improper contraction and/or relaxation of the heart. This can lead to cardiac arrhythmias, heart failure and even sudden cardiac death, sometimes in young individuals. Often these cardiomyopathies are inherited and research already enabled identification of more than 60 genes associated with these disorders. But in more than half of the patients no mutations are detected in any of the known genes and the genetic cause remains elusive. Through study of these disease genes new insight has already been gained in the pathophysiological mechanisms causing cardiomyopathies, but the picture remains far from complete. At present, there are some therapeutic options to reduce disease symptoms, but therapies that are capable of completely stopping or even reversing the disease are not yet available.

Goal

We aim to further investigate the genetic causes and disease mechanisms underlying cardiomyopathies. This will lead to a significantly improved understanding of the disorders and provide the possibility to develop novel therapies. With our research team we aim to improve genetic diagnosis, risk prediction, optimize counseling and deliver true personalized management of patients to increase their quality of life.

Strategy

Using modern DNA sequencing techniques (including whole-exome and whole-genome sequencing) in patients without a genetic diagnosis, we will identify novel genes involved in cardiomyopathies. We are also focusing on the identification of genetic modifiers that play a role in the development of these disorders and can explain the phenotypic variability observed within families. The functional effect of mutations in these genes and modifiers are studied in patient samples, induced pluripotent stem cell (iPSC)-derived cardiac cells and transgenic zebrafish or mice. Hereto we are using state-of-the-art techniques such as CRISPR/Cas genome editing, transcriptomics, interactomics, proteomics, high-tech microscopy and micro-electrode arrays. Based on these novel insights, new therapeutic targets can be identified for which novel drugs can be tested in the pre-clinical disease models that we generated.

Disorders under investigation:

Hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, non-compaction cardiomyopathy.

Team members:

Bart Loeys, Maaike Alaerts, Ewa Sieliwonczyk, Hanne Boen, Laura Rabaut, Maaike Bastiaansen, Jarl Bastianen, Jolien Schippers, Sofie Daemen, Charlotte Claes