The human heart does not function in isolation. Increasing evidence suggests that the intestinal microbial ecosystems play a crucial role in cardiovascular health.
Our laboratory investigates how gut microbial dysbiosis influences cardiac physiology and disease progression, particularly in heart failure.
Rather than focusing solely on correlations, we aim to uncover causal molecular mechanisms linking the gut microbiome to cardiac pathology.

We combine:

• Metagenomics

• Metabolomics

• Proteomics

• Host transcriptomics

• Single-bacterial RNA sequencing

to identify microbial species, pathways, and metabolites that actively influence cardiac signaling and inflammation.

A unique strength of our laboratory is the implementation of single-bacterial RNA sequencing, a cutting-edge technology recently established in our lab with support from the Heidelberger-Herz-Stiftung. This approach allows us to explore microbial activity at an unprecedented resolution and understand how individual bacterial cells contribute to host-disease signaling networks. By integrating data from human patient biospecimens and mechanistic animal models, we aim to reveal how the gut microbiome becomes a functional regulator of cardiac health.

Cardiomyocytes rely on tightly regulated protein quality control systems to maintain cellular integrity under stress. Central to this system is the Ubiquitin Proteasome System (UPS), which governs selective protein degradation and signaling. Our laboratory investigates how E3 ubiquitin ligases regulate cardiac proteostasis and signaling pathways during physiological adaptation and pathological remodeling. We are particularly interested in understanding the cardiac roles of E3 ligases such as:

• HectD3

• TRIM24

• TRIM32

These enzymes determine substrate specificity in ubiquitination, thereby controlling diverse processes including:

• cardiac hypertrophy

• inflammatory signaling

• metabolic remodeling

• ion channel regulation

• cardiomyocyte survival

Using genetic animal models, multi-omics approaches, and advanced metabolic phenotyping, we aim to identify novel substrates and signaling pathways regulated by these E3 ligases. Deciphering these pathways may open new therapeutic opportunities to restore proteostasis and prevent heart failure progression.

Cardiovascular diseases arise from complex molecular alterations that disrupt both the structural integrity and metabolic capacity of the heart. Mitochondria play a central role in cardiac energy production, calcium signaling, and metabolic adaptation.

Our research focuses on understanding how cardiac structural proteins communicate with mitochondrial regulators to maintain cardiomyocyte function. We identified SH3BGR, a cardiac protein essential for sarcomere stability and cell survival, and found that its dysregulation destabilizes the contractile apparatus and activates stress-responsive pathways such as RhoA–SRF and Hippo signaling, ultimately promoting cardiomyocyte dysfunction and cell death. Importantly, we discovered that SH3BGR interacts with LETM1, an inner mitochondrial membrane protein involved in mitochondrial ion transport, revealing an unexpected molecular link between the cardiac cytoskeleton and mitochondrial function.

Our lab has recently initiated research into LETM1, an inner mitochondrial membrane protein proposed to function as a Ca²⁺/K⁺ uniporter.

Although LETM1 has been implicated in mitochondrial ion balance, its role in cardiac physiology and disease remains largely unexplored.

We aim to determine:

• how LETM1 regulates mitochondrial ion homeostasis

• how mitochondrial Ca²⁺ handling affects cardiomyocyte metabolism and contractility

• whether dysregulation contributes to cardiac remodeling and heart failure

By combining metabolic assays, mitochondrial physiology, and systems-level omics analyses, we seek to uncover new links between mitochondrial signaling and cardiac disease mechanisms.