Intercellular communication dynamics of macrophages and cardiomyocytes across dilated cardiomyopathy (DCM) phenogroups

• Applicant: Dr. Tobias Lerchner
• Subject Area: Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 569395831

The primary objective is to address the yet unmet need to advance the pathophysiological understanding of DCM. Thus, enabling a holistic understanding of this heterogenous disease, and to achieve personalized treatment options of this vulnerable patient cohort often presenting with severe, end stage heart failure requiring transplantation. In this project, the key objective is to enhance the understanding of autoimmunity and global inflammation associated with DCM, focusing on the macrophage-cardiomyocyte crosstalk. While understanding this crosstalk in different DCM phenogroups, a holistic understanding will lead the way to novel anti-inflammatory treatment options in the future. The applicant will pursue an integrative approach, enabled by several unique breakthrough technologies (e.g., integrative single-cell resolution imaging and metabolomics) and expert knowledge on cardiac fibrosis and macrophage biology, as well as strategic collaborations. The applicant aims to unravel a yet underrepresented part in DCM research, the epigenetic signature, especially focussing on lysine demethylase 8. He aims to identify key epigenetic mechanisms underlying DCM. Further, the applicant aims to elucidate a deepened understanding of the impact of epigenetic signaling in different DCM patient cohorts to unravel potential new therapeutic targets and the immune-epigenetic crosstalk. Additionally, he would like to give an outlook to a project after his time at CARIM. Here, in a collaboration between the West German Heart and Vascular Center Essen and CARIM, the applicant aims to unravel the impact of clonal hematopoiesis on peripheral immune cells driving inflammation and cardiac dysfunction, to be able to pinpoint the systemic distribution and to underly the hypothesis that DCM progression leads to immune-mediated changes affecting various organ systems. This whole project is not only expected to lead to unprecedented insights into aberrant cardiomyocyte-macrophage crosstalk and epigenetics, but also, guided by this knowledge, to new crosstalk-based targets for intervention in this highly heterogenous and vulnerable patients.

• DFG Programme: WBP Fellowship
• International Connection: Netherlands
• Host: Professor Dr. Stephane Heymans