Selected work & patents

Anthracyclines such as doxorubicin remain a cornerstone of cancer therapy, but their cardiotoxic side effects are still incompletely understood and no broadly effective preventive strategy exists. This study identifies a new mechanistic link between doxorubicin-induced topoisomerase IIb activity and MEF2-driven pathological gene expression in cardiomyocytes, showing that doxorubicin preferentially recruits topoisomerase IIb to MEF2-associated cardiac gene promoters and thereby boosts MEF2 activity.

The pan-HDAC inhibitor SAHA counteracts this response, but only when HDAC4 is present: SAHA promotes acetylation of the chaperone 14-3-3, which disrupts its binding to HDAC4/5, keeps these class IIa HDACs in the nucleus, and represses MEF2-driven transcription. In mice, SAHA co-treatment reduced doxorubicin-induced cardiac dysfunction and fibrosis, while cardiomyocyte-specific loss of HDAC4 abolished this protection. The findings position HDAC inhibition as a potential cardioprotective repurposing strategy alongside anthracycline chemotherapy.

MCL-1 is a key anti-apoptotic protein and an attractive oncology drug target, but early clinical trials of MCL-1 inhibitors showed unexpected troponin elevations, raising cardiotoxicity concerns that conventional mouse models capture only incompletely due to species differences in MCL-1 pharmacology. Using a humanised MCL-1 mouse model, we treated animals weekly with the selective inhibitor MIK665 and assessed cardiac biomarkers, echocardiographic function, and myocardial transcriptomics at peak treatment (day 14) and after treatment cessation (day 21).

Troponin T rose over the treatment course without measurable loss of left ventricular systolic function. RNA sequencing showed coordinated downregulation of mitochondrial and contractile gene programmes together with activation of stress- and immune-related pathways during treatment; after cessation, troponin fell and the transcriptome shifted to a distinct recovery signature. No overt systolic dysfunction, strain abnormalities or increased fibrosis were detected, pointing to a largely reversible cardiac stress response rather than structural cardiotoxicity – supporting humanised models for improved translational cardiac safety testing.

This study investigates circulating musclin as a biomarker connecting skeletal muscle function and subclinical cardiac dysfunction in patients with cancer, pointing to a shared pathway between cancer-associated muscle wasting and early cardiac impairment.

This study examines how acute coronary syndrome impacts long-term survival in cancer patients, providing important prognostic data for this vulnerable patient population.

This paper investigates the prevalence of coronary artery disease in patients with an underlying oncological disease and elevated troponin. A key finding is that around 10% of asymptomatic patients with elevated troponin-T had coronary artery disease requiring intervention; classic risk factors such as smoking, elevated BMI and pre-existing coronary artery disease emerged as predictive markers.

This prospective cohort study followed 137 patients treated with CAR T-cell constructs at Heidelberg University Hospital, with cardiac biomarkers, ECG, and echocardiography assessed from before lymphodepletion through six months after infusion. The aim was to test whether classical cardiovascular risk factors and cardiac biomarkers can predict all-cause mortality and cardiotoxicity in this population.

A thickened septal wall before treatment was associated with a higher risk of death, with a similar trend for a reduced pre-treatment ejection fraction. Most strikingly, a rise in high-sensitivity troponin T of 50% or more within the first two weeks after infusion predicted all-cause mortality, whereas no single baseline parameter reliably predicted cardiac events. The findings suggest that pre-existing cardiac impairment and early biomarker kinetics could help identify patients who would benefit from closer cardio-oncological surveillance during CAR T-cell therapy.

Anthracyclines such as doxorubicin remain a cornerstone of cancer therapy, but their cardiotoxic side effects are still incompletely understood and no broadly effective preventive strategy exists. This study identifies a new mechanistic link between doxorubicin-induced topoisomerase IIb activity and MEF2-driven pathological gene expression in cardiomyocytes, showing that doxorubicin preferentially recruits topoisomerase IIb to MEF2-associated cardiac gene promoters and thereby boosts MEF2 activity.

The pan-HDAC inhibitor SAHA counteracts this response, but only when HDAC4 is present: SAHA promotes acetylation of the chaperone 14-3-3, which disrupts its binding to HDAC4/5, keeps these class IIa HDACs in the nucleus, and represses MEF2-driven transcription. In mice, SAHA co-treatment reduced doxorubicin-induced cardiac dysfunction and fibrosis, while cardiomyocyte-specific loss of HDAC4 abolished this protection. The findings position HDAC inhibition as a potential cardioprotective repurposing strategy alongside anthracycline chemotherapy.

This publication represents a pivotal step in advancing cardio-oncology by identifying and validating cardio-muscular biomarkers that allow the diagnosis and risk stratification of Immune Checkpoint Inhibitor (ICI)-associated myocarditis. Through integration of large-scale registry analysis, the study moves beyond conventional cardiac markers, introducing cut-offs for clinical decision making. It establishes a benchmark for biomarker-driven management of ICI myocarditis and sets a visionary precedent for personalized, immune-toxicology-guided cardiology.

This publication presents the first transcriptomic analysis of myocardial biopsies from patients with immune checkpoint inhibitor (ICI)-associated myocarditis. The study identifies Guanylate Binding Protein 5 (GBP5) as significantly dysregulated, suggesting its involvement in cardiac inflammatory responses. The integration of human biopsy data into cardio-immunology research underscores the potential of tissue-level transcriptomics to refine biomarker discovery and pathophysiological understanding.

This study uncovers a previously unrecognized epigenetic-metabolic signaling axis in the heart, linking a proteolytic fragment of HDAC4 to regulation of the hexosamine biosynthetic pathway. The findings demonstrate how neurohumoral stress can induce lasting metabolic reprogramming via chromatin-linked mechanisms. This work has opened new avenues for targeting metabolic remodeling in heart failure and has influenced subsequent research on cardiac epigenetics.