Selected work & patents

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 observational study characterizes the cardiotoxic effects of BRAF/MEK inhibitor therapy in melanoma patients, contributing real-world safety data for this widely used targeted-therapy combination.

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 study sheds new light on the epigenetic control of cardiac gene expression by demonstrating how loss of HDAC4 disrupts global transcriptional repression through H3K9 methylation. Using a cardiomyocyte-specific knockout model, we show that HDAC4 deletion leads to heightened transcriptional responsiveness, revealing a critical buffering role for HDACs in maintaining genomic stability. It shows how epigenetic changes precede transcriptional changes and opens a route for early identification of disease phenotypes.

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.

This landmark study uncovered a previously unrecognized neurohumoral feedback loop in heart failure by showing that endothelin A receptors on sympathetic neurons impair norepinephrine reuptake, thereby exacerbating cardiac stress. By bridging neurobiology and cardiology, it proposes the peripheral nervous system as a therapeutic target in heart failure and initiated novel strategies to modulate sympathetic outflow in chronic cardiac disease.