Deciphering molecular circuits of cardiac remodeling and dysfunction via an integrative reverse approach
Project B10 is a canonical data integration project aiming to identify key molecular circuits for cardiac remodeling and dysfunction. B10 will develop and apply novel and state of the art computational methods to integrate bulk and single-cell OMICs data from several dedicated mouse models as well as public data from patients. From these analyses we […]
Unraveling molecular circuits leading to catecholamine driven ventricular arrhythmias
We identified OCaR2 as a regulator of lysosomal two-pore channels, and its deletion resulted in Ca2+ oscillations in cardiomyocytes causing fatal catecholaminergic arrhythmias. We combine Ca2+ imaging, ECG telemetry, transcriptome and metabolome approaches with computational methods to elucidate pathways and patterns of gene regulation. By comparative analysis of circuits in arrhythmogenic cardiomyopathy models, we aim […]
Role of ETV transcription factors in atrial cardiomyopathy
Atrial cardiomyopathy is a complex and heterogenous disease and efficient therapies are lacking. ETV transcription factors driven gene regulation was shown for various genes as KCNK3 that are involved in atrial remodeling processes. We will dissect how ETV1-7 transcription factors are involved in the regulation of the atrial KCNK3 potassium ion channel as well as […]
Control of cardiac homeostasis and cardiocrine signaling by protein arginine methyltransferases
Protein arginine methyltransferases are strongly down-regulated in failing human hearts. Our preliminary work unmasked that PRMT5 and PRMT7 exert strong cardiomyocyte-intrinsic effects on splicing and histone methylation along with essential functions for mitochondrial function, cardiac contractility and microenvironmental integrity. Together with other CRC 1550 projects, B07 will undertake an integrative approach to decode Prmt5-/Prmt7-dependent cardiomyocyte-intrinsic […]
Cardiocrine signaling as a regulator of cardiac homeostasis and fibrosis
Cardiomyocytes communicate with their surrounding cells through mechanical and chemical interactions. A novel mass spectrometry based approach enabled us to characterize the secretome of primary cardiomyocytes. For this proposal, we will investigate down-stream paracrine and autocrine effects of the identified, most strongly regulated signal proteins under hypoxia. In addition, we will determine their up-stream regulation […]
The role of the AP-1 transcriptional complex during cardiac remodeling
Cardiovascular disease accounts for a large proportion of morbidity and mortality worldwide. We, and others, have shown that AP-1 transcription factors (TFs) play a role in remodeling the cardiomyocyte chromatin landscape in response to injury. Here, we aim to gain detailed insight into the molecular networks regulated by the AP-1 family of TFs during myocardial […]
The role of unconventional RNA-Binding proteins in the failing heart
In addition to the established role of RNA-binding proteins (RBPs) affecting post-transcriptional steps in gene expression, RNA-binding also regulate the function, activity, structure, or location of so called “unconventional” RBPs. This phenomenon has been termed “riboregulation”. We identified cardiomyocyte specific proteins surprisingly as RBPs, such as the sarcoplasmic reticulum calcium ATPase 2 (SERCA2a) and the […]
Impact of the translation elongation factor 1a on cardiac growth and function
Heart growth after birth or during disease involves increased protein synthesis and reduced protein degradation. The cardiac function of one putative regulator of both processes, the eukaryotic elongation factor 1 (EEF1A) was so far not studied, but recently a gene-mutation in this protein was associated with human cardiomyopathy. We therefore hypothesize that EEF1A, expressed in […]