Alternative molecular disease pathways in the presence of troponin complex mutations in cardiomyopathy (A12)

• Subject Area: Anatomy and Physiology
• Term: from 2016 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 193793266

In A12, we will analyze the consequences of disrupted sarcomere-microfilament interactions using iPSC-cardiomyocytes with cardiomyopathy mutations (MUT iPSC-CMs) and heart tissue samples. Resulting alternative disease pathways include defective interactions in plasma membrane microdomains in MUT iPSC-CMs, which lead to impaired clathrin-dependent endocytosis. This may cause dysfunctional trafficking of endosomal cargo such as transferrin-bound iron, which may contribute to dysregulated mitochondrial metabolism and enhanced disease phenotypes in MUT iPSC-CMs. Our future results will add to the understanding of molecular dysfunctions in cardiomyopathy due to troponin complex mutations and will contribute to the characterization of future druggable targets in heart failure.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1002: Modulatory Units in Heart Failure
• Applicant Institution: Georg-August-Universität Göttingen
• Project Head: Privatdozentin Dr. Antje Dagmar Ebert