A5059199729- Pluripotent Stem Cells Research
- Congenital heart defects research
- Cardiac electrophysiology and arrhythmias
- CRISPR and Genetic Engineering
- Neuroscience and Neural Engineering
- Tissue Engineering and Regenerative Medicine
- Liver Disease Diagnosis and Treatment
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Cardiac Fibrosis and Remodeling
- Hepatitis C virus research
- Liver Disease and Transplantation
- Congenital Heart Disease Studies
- Muscle Physiology and Disorders
- Virus-based gene therapy research
- Cardiovascular Effects of Exercise
- Diverticular Disease and Complications
- Inflammatory Bowel Disease
- Neuroendocrine Tumor Research Advances
- Microscopic Colitis
- Liver Diseases and Immunity
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Neuroblastoma Research and Treatments
- Viral Infections and Immunology Research
German Centre for Cardiovascular Research
2016-2025
Klinikum rechts der Isar
2016-2025
Technical University of Munich
2016-2025
München Klinik
2005-2024
Ospedale San Filippo Neri
2007-2024
Yale University
2023
Bavarian Research Alliance
2019-2021
University of Applied Sciences and Arts of Southern Switzerland
2015
Università della Svizzera italiana
2015
University of Modena and Reggio Emilia
2014
Long-QT syndromes are heritable diseases associated with prolongation of the QT interval on an electrocardiogram and a high risk sudden cardiac death due to ventricular tachyarrhythmia. In long-QT syndrome type 1, mutations occur in KCNQ1 gene, which encodes repolarizing potassium channel mediating delayed rectifier IKs current.
Analyzing contractile force, the most important and best understood function of cardiomyocytes in vivo is not established human induced pluripotent stem cell-derived (hiPSC-CM). This study describes generation 3D, strip-format, force-generating engineered heart tissues (EHT) from hiPSC-CM their physiological pharmacological properties. CM were differentiated hiPSC by a growth factor-based three-stage protocol. EHTs generated analyzed histologically functionally. HiPSC-CM showed...
Abstract Coordinated release of calcium (Ca 2+ ) from the sarcoplasmic reticulum (SR) through cardiac ryanodine receptor (RYR2) channels is essential for cardiomyocyte function. In catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited disease characterized by stress‐induced arrhythmias in young patients with structurally normal hearts, autosomal dominant mutations RYR2 or recessive calsequestrin lead to aberrant diastolic Ca SR causing arrhythmogenic delayed after...
Abstract The epicardium, the mesothelial envelope of vertebrate heart, is source multiple cardiac cell lineages during embryonic development and provides signals that are essential to myocardial growth repair. Here we generate self-organizing human pluripotent stem cell-derived epicardioids display retinoic acid-dependent morphological, molecular functional patterning epicardium myocardium typical left ventricular wall. By combining lineage tracing, single-cell transcriptomics chromatin...
Abstract Frameshift mutations in the TTN gene encoding titin are a major cause for inherited forms of dilated cardiomyopathy ( DCM ), heart disease characterized by ventricular dilatation, systolic dysfunction, and progressive failure. To date, there no specific treatment options patients but transplantation. Here, we show beneficial potential reframing transcripts antisense oligonucleotide AON )‐mediated exon skipping human murine models carrying previously identified autosomal‐dominant...
Calmodulin (CaM) is a small protein, encoded by three genes (CALM1-3), exerting multiple Ca2+-dependent modulatory roles. A mutation (F142L) affecting only one of the six CALM alleles associated with long QT syndrome (LQTS) characterized recurrent cardiac arrests. This phenotypic severity unexpected from predicted allelic balance. In this work, effects heterozygous CALM1-F142L have been investigated in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) obtained LQTS...
Heterozygous truncating variants in TTN (TTNtv), the gene coding for titin, cause dilated cardiomyopathy (DCM), but underlying pathomechanisms are unclear and disease management remains uncertain. Truncated titin proteins have not yet been considered as a contributor to development. Here, we studied myocardial tissues from nonfailing donor hearts 113 patients with end-stage DCM expression identified TTNtv 22 (19.5%). We directly demonstrate haploinsufficiency TTNtv-DCM absence of...
Pathological cardiac hypertrophy is a result of afterload-increasing pathologies including untreated hypertension and aortic stenosis. It features progressive adverse remodeling, myocardial dysfunction, capillary rarefaction, interstitial fibrosis often leading to heart failure. This study aimed establish novel porcine model pressure-overload–induced failure determine the effect inhibition microribonucleic acid 132 (miR-132) on development in this model. developed percutaneous constriction...
By combining single-channel and whole-cell patch-clamp recordings, we have established the sensitivity to ω-agatoxin IVA ω-conotoxin MVIIC (SNX-230) of G1, G2, G3, three novel non-L-, non-N-type Ca 2+ channels characterized previously in rat cerebellar granule cells. G1 were blocked irreversibly by both low doses (saturation at 50 n m ). Thus, according pharmacological criteria, must be classified as P-type channels. Being slowly inactivating during depolarizing pulses completely inactivated...
Ectopic expression of defined sets genetic factors can reprogram somatic cells to create induced pluripotent stem (iPS) cells. The capacity direct human iPS specific differentiated lineages and their progenitor populations be used for disease modeling, drug discovery, eventually autologous cell replacement therapies. During mouse cardiogenesis, the major mature heart, cardiomyocytes, smooth muscle cells, endothelial arise from a common, multipotent cardiovascular expressing transcription...
During cardiogenesis, most myocytes arise from cardiac progenitors expressing the transcription factors Isl1 and Nkx2-5. Here, we show that a direct repression of by Nkx2-5 is necessary for proper development ventricular myocardial lineage. Overexpression in mouse embryonic stem cells (ESCs) delayed specification inhibited expression its downstream targets Isl1(+) precursors. Embryos deficient lineage failed to downregulate protein cardiomyocytes heart tube. We demonstrated directly binds an...