Kliniken & Institute … Kliniken Zentrum für Innere… Internal Medicine III:… Research Molecular… Basic Research

Basic Research

Molecular Mechanism of anthracycline-induced cardiotoxicityOur basic resarch has a focus on cardiac metabolism, epigenetics and cardio-oncology. Based on our previous work on histone deacetylases (HDAC), we study epigenetic consequences of cancer and cancer therapies on the heart. In particular, we are interested in the cardiac epigenetic alterations by anthracyclines and investigate cardiac consequences in different preclinical cancer models. This project is currently funded by the German Research Foundation (DFG).

Midkine, a metabolic signaling transmitter – In this project, we found the heparin-binding growth factor as a potential signaling protein between the heart and cancer. We currently investigate the role of cardiac midkine in the progression of certain oncological disease in preclinical models. This project is funded by the German Centre for Cardiovascular Research (DZHK)

Epigenetic memory of metabolic stress – In our previous work, we have found that epigenetic changes do not directly lead to transcirptional changes. More importantly, epigenetic alterations seem to predict further transcriptional response on cardiac stress. We have identified a large genomic region that is highly regulated upon metabolic stress. Currently we investigate conditional genetic deletion of these regions to understand the biological effects of these epigenetic changes.

Role of the cardiac Inflammasome in checkpoint-inhibitor-associated myocarditis – By systematic analysis of the human cardiac transcriptome, we identified genes of the cardiac inflammasome as highly dysregulated in patients with myocarditis. We currently generate conditional preclinical models to investigate potential protective strategies for the treatment of cardiac inflammation.

Metabolic signaling of cardiac nuclear receptors – Based on our previous work, we have identified nuclear receptors to be important for the regulation of cardiac metabolic response. Currently we investigate the molecular pathways (binding partner and transcriptional regulation) of these receptors to understand and to manipulate ther physiological function.

In unseren laufenden Projekten untersuchen wir die vor- und nachgelagerten Signalwege von nukleären Rezeptoren sowie die metabolische Signalübertragung auf das kardiale Epigenom. Grundlage hierfür sind mechanistische Arbeiten zur adrenergen Beta-Signalübertragung. Abbildung modifiziert aus Lehmann et al.