Kliniken &… Kliniken Zentrum für Innere… Innere Medizin III:… Forschung Arbeitsgruppen Grundlagenforschung … Experimental Cardiology… Research Focus

Experimental Cardiology and Gut-Heart Axis

Research Focus

Heart disease is the leading cause of deaths worldwide. Disturbed cardiac protein homeostasis and chronic inflammation due to various factors, including altered gut microbiome (and its metabolic products) are emerging as major contributor to the deteriorating cardiac function.

Ubiquitin Proteasome System plays crucial role in cardiac protein homeostasis. E3 ubiquitin ligases, which mediate the final step in protein ubiquitination (Figure 1) and also provide the substrate recognition specificity, have recently been implicated in various cardiac processes and pathologies like heart development, signaling cascades, ion channel regulation, autophagy regulation, protein degradation, congenital heart diseases and cardiomyopathies. We are interested in deep understanding of how and through which substrates E3 ligases impact cardiac function in order to use this knowledge for future therapeutic approaches.

Figure 1: Ubiquitination process. Ubiquitination is accomplished by the concerted action of three enzymatic steps involving E1 activating enzymes, E2 conjugating enzymes, and E3 ligases.

Similarly, altered gut microbiome also termed as “gut-dysbiosis” is increasingly being associated with heart failure. We and others have found strong correlation between changes in gut microbial content with the extent of failing heart. Deciphering the underlying mechanisms and specific molecules derived from these studies are necessary to understand if this correlation can be therapeutically targeted. Using state-of-the-art Multi-OMICs technologies, we aim to unearth these associations.

Research Techniques

  • Classic Molecular Biology techniques
  • Reporter- and Seahorse-assays
  • Transgenic animals
  • Metagenomics
  • metabolomics and proteomics