Arrhythmogenic Cardiomyopathy: Investigation of new mechanisms and therapeutic targets
(SNSF Starting Grant)
We address multiple stages of the pathological cascade associated with ACM:
- Integration of functional and molecular data:
By combining cardiac functional analyses with spatial and temporal gene expression patterns, we identify causative and predictive factors driving arrhythmias and cardiac fibrosis.
- Cell-type–specific mechanisms:
We investigate how distinct cardiac cell subtypes contribute to disease manifestation and progression, and how their interactions shape the cardiomyopathy phenotype.
- Therapeutic strategies:
A key focus lies on evaluating compounds that restore impaired cell–cell adhesion, building on our findings that disrupted intercellular adhesive function plays a central role in ACM pathogenesis (Schinner et al., Circulation, 2022).
Methodological Expertise
To explore ACM in vitro, ex vivo, and in vivo, we employ a range of methods:
- Molecular and omics-based analyses:
- Transcriptomics (spatial transcriptomics, single-cell and single-nucleus RNA sequencing)
- Proteomics (total and phospho-proteomes)
- Additional biomolecular analyses of disease-relevant pathways
- Structural analyses:
- Histological techniques and fluorescence-based imaging
- Electron microscopy for ultrastructural assessment
- Functional analyses:
- In vivo cardiac function assessment (echocardiography, ECG)
- Adhesion assays (low- and high-throughput) to quantify defects in cell–cell interactions
- Advanced disease modeling:
We establish novel ACM model systems, including stem cell-derived 3D heart tissue, to recapitulate disease features and enable preclinical testing of therapeutic approaches.
