https://gepris.dfg.de/gepris/projekt/318243743
Title: Wnt/beta-catenin/TCF-dependent transcriptional regulation in heart failure (Wnt/beta-catenin/TCF-abhängige Transkriptionsregulation in der Herzinsuffizienz)
Wnt/ß-catenin activation results in the development of cardiac dysfunction. In this project, the hypothesis will be tested that enhanced Wnt/ß-catenin activity triggers a cell-specific gene expression programs in cardiomyocytes (CM) and cardiac fibroblasts (FB), which contribute to disease progression. We will define both (I) the consequences of Wnt/ß-catenin activation and (II) the effect of ß-catenin loss of function at different stages of disease progression upon pressure overload in CM und FB in the mouse. Wnt components will be analysed in myocardium patient samples with aortic stenosis. (III) We will also test the suitability of a specific inhibition of the Wnt/ß-catenin /TCF7L2-dependent transcriptional activity to prevent heart failure progression.
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Created: 2nd Feb 2022 at 13:56
Last updated: 23rd Aug 2023 at 15:13
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Projects: CRC1002: Modulatory Units in Heart Failure, Cardiomyocyte tissues, TRR 274: Checkpoints of Central Nervous System Recovery, SFB 1190: Compartmental Gates and Contact Sites in Cells, MBExC: Multiscale Bioimaging, CRC 1565: Molecular mechanisms and interplay of gene expression processes
Institutions: University Medical Center Göttingen
https://orcid.org/0000-0003-1236-0815Projects: Default Project - for test purposes, CRC1002: Modulatory Units in Heart Failure, Cardiomyocyte tissues, TRR 274: Checkpoints of Central Nervous System Recovery, SFB 1190: Compartmental Gates and Contact Sites in Cells, MBExC: Multiscale Bioimaging, CRC 1565: Molecular mechanisms and interplay of gene expression processes
Institutions: Default Institution, University Medical Center Göttingen, Georg-August-Universität Göttingen
https://orcid.org/0000-0002-9895-2469Expertise: Data Management, Bioinformatics, Molecular Biology, Microbiology
Tools: Proteomics, sequencing, RNA-seq, Genomics
Projects: CRC1002: Modulatory Units in Heart Failure
Institutions: University Medical Center Göttingen
https://orcid.org/0000-0002-9001-0346Expertise: Cardiology, Molecular Biology, Bioinformatics
Tools: sequencing
Projects: CRC1002: Modulatory Units in Heart Failure, TRR 274: Checkpoints of Central Nervous System Recovery, SFB 1190: Compartmental Gates and Contact Sites in Cells
Web page: Not specified
https://sfb1002.med.uni-goettingen.de/ (Research Data Platform) https://gepris.dfg.de/gepris/projekt/193793266?language=en (DFG Gepris entry) With a prevalence of between two and four percent, heart failure remains one of the most common diseases in Europe. Although tremendous progress has been made in its treatment, the morbidity and mortality of affected patients remains high. Advanced heart failure can still only be treated palliatively.We define modulatory units as cell-based and/or genetic ...
Programme: Sonderforschungsbereiche/Collaborative Research Centers
Public web page: https://herzzentrum.umg.eu/forschung/forschungsverbuende/sfb-1002/
Start date: 1st Jul 2012
End date: 30th Jun 2024
Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing Corresponding publication:
https://sfb1002.med.uni-goettingen.de/production/literature/publications/201
(https://doi.org/10.1093/nar/gky049)
Submitter: Harald Kusch
Investigation: CRC1002 Project C07 (2016-2024)
Assays: ChIP Seq, RNA Seq, echocardiographic analysis, immunocytochemistry
Snapshots: No snapshots
Activation of the evolutionarily conserved, developmental Wnt pathway has been reported during maladaptive cardiac remodeling. Although the function of Wnt-transcriptional activation in development is well described, the consequences of Wnt pathway activation, as well as its cardiac-specific regulatory role in the adult heart, is largely unknown. We show that β-catenin and Transcription factor 7-like 2 (TCF7L2), the main nuclear components of the Wnt-transcriptional cascade, and their transcriptional ...
Submitter: Harald Kusch
Assay type: Gene Expression Profiling
Technology type: Chip-seq
Investigation: CRC1002 Project C07 (2016-2024)
Organisms: No organisms
SOPs: No SOPs
Data files: 1 hidden item
Snapshots: No snapshots
Summary: Activation of the evolutionarily conserved, developmental Wnt pathway has been reported during maladaptive cardiac remodeling. Although the function of Wnt-transcriptional activation in development is well described, the consequences of Wnt pathway activation, as well as its cardiac-specific regulatory role in the adult heart, is largely unknown. We show that β-catenin and Transcription factor 7-like 2 (TCF7L2), the main nuclear components of the Wnt-transcriptional cascade, and their ...
Submitter: Harald Kusch
Assay type: Gene Expression Profiling
Technology type: Rna-seq
Investigation: CRC1002 Project C07 (2016-2024)
Organisms: No organisms
SOPs: No SOPs
Data files: 3 hidden items
Snapshots: No snapshots
Transaortic constriction (TAC) was done in 12-weeks-old mice. Pre-anesthetic and anesthetic agents are listed in Supplemental Table S2. The intervention was performed by tying a braided 5–0 polyviolene suture (Hugo Sachs Electronik) ligature around the aorta and a blunted 26-gauge needle and subsequent removal of the needle. For sham controls, the suture was not tied. To determine the level of pressure overload by aortic ligation, a high frequency Doppler probe was used to measure the ratio between ...
Submitter: Harald Kusch
Assay type: Echocardiographic analysis
Technology type: micro-ultrasound imaging
Investigation: CRC1002 Project C07 (2016-2024)
Organisms: No organisms
SOPs: No SOPs
Data files: 1 hidden item
Snapshots: No snapshots
Submitter: Harald Kusch
Assay type: Experimental Assay Type
Technology type: Technology Type
Investigation: CRC1002 Project C07 (2016-2024)
Organisms: No organisms
SOPs: No SOPs
Data files: 1 hidden item
Snapshots: No snapshots
Abstract (Expand)
Authors: L. M. Iyer, S. Nagarajan, M. Woelfer, E. Schoger, S. Khadjeh, M. P. Zafiriou, V. Kari, J. Herting, S. T. Pang, T. Weber, F. S. Rathjens, T. H. Fischer, K. Toischer, G. Hasenfuss, C. Noack, S. A. Johnsen, L. C. Zelarayan
Date Published: 6th Apr 2018
Publication Type: Journal
PubMed ID: 29394407
Citation: Nucleic Acids Res. 2018 Apr 6;46(6):2850-2867. doi: 10.1093/nar/gky049.