Research
Our lab investigates intracellular signaling pathways that regulate cardiac hypertrophy and heart failure. We combine molecular biology, phosphoproteomics, and advanced cardiomyocyte models to understand disease mechanisms and identify novel therapeutic targets.
01 / 04
STRIPAK Signaling
Our group identified Myoscape (STRIP2) as a cardiac-specific component of the STRIPAK complex that regulates L-type calcium channel surface expression, thereby controlling cardiac calcium homeostasis and contractility (Eden et al., Nat Commun 2016). Recently, we demonstrated that the STRIPAK-associated kinase MST4 regulates cardiomyocyte growth and survival and is upregulated in human cardiomyopathy (Eden et al., J Biol Chem 2024). Additionally, we investigate protein interaction networks involving the BLOC-1 complex and Dysbindin that modulate STRIPAK signaling in the heart (Borlepawar et al., Cells 2020).
02 / 04
M-Band Signaling
We identified Myomasp/LRRC39 as a heart- and muscle-specific protein that constitutes a novel component of the sarcomeric M-band involved in mechanical stretch sensing (Will, Eden et al., Circ Res 2010). In parallel, we showed that cardiac overexpression of the intercalated disc protein Myozap causes a protein-aggregate-associated cardiomyopathy (Frank, Rangrez, Eden et al., J Mol Cell Cardiol 2014), while Myozap deficiency promotes adverse cardiac remodeling through differential regulation of MAPK/SRF and β-catenin/GSK-3β signaling (Rangrez, Eden et al., J Biol Chem 2016).
03 / 04
Stretch Sensing
Our research investigates how cardiomyocytes sense mechanical load and translate it into cellular responses. We characterized Myomasp/LRRC39 as a sarcomeric mechanosensor at the M-band that detects stretch stimuli (Will, Eden et al., Circ Res 2010). Through Myoscape/STRIP2, we elucidated a mechanism by which mechanical signals regulate L-type calcium channel surface expression and thereby excitation-contraction coupling (Eden et al., Nat Commun 2016). Furthermore, we explore the role of Filamin C in cardiac filaminopathies and its divergent significance for human cardiomyopathies (Eden & Frey, J Clin Med 2021).
04 / 04
Cardiac Hypertrophy
The Calcineurin-NFAT signaling axis is a central research focus of our group. With the discovery of Calsarcins as sarcomeric calcineurin-binding proteins (Frey et al., PNAS 2000) and the demonstration that Calsarcin-1 deficiency sensitizes calcineurin signaling and accelerates pathological hypertrophy (Frey et al., Nat Med 2004), we defined a novel regulatory mechanism. Calsarcin-2 deficiency, in contrast, increases exercise capacity via Calcineurin/NFAT activation (Frey et al., J Clin Invest 2008). We further showed that SUMO2 activates Calcineurin-NFAT signaling in a sumoylation-independent manner, thereby promoting cardiomyocyte hypertrophy (Bernt, Rangrez, Eden et al., Sci Rep 2016). Currently, we are investigating metabolic approaches: AAV-mediated CPT1B overexpression protects against hypertrophy and heart failure in a murine pressure overload model (Kliesow Remes et al., Basic Res Cardiol 2025).