A5023831801- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- Cardiac electrophysiology and arrhythmias
- Pluripotent Stem Cells Research
- Ion channel regulation and function
- Tissue Engineering and Regenerative Medicine
- Receptor Mechanisms and Signaling
- Neural dynamics and brain function
- Molecular Communication and Nanonetworks
- Neuroscience and Neuropharmacology Research
- Connexins and lens biology
- CRISPR and Genetic Engineering
- Retinal Development and Disorders
- Congenital heart defects research
- Nicotinic Acetylcholine Receptors Study
- 3D Printing in Biomedical Research
- Photochromic and Fluorescence Chemistry
- S100 Proteins and Annexins
- Mitochondrial Function and Pathology
- Planarian Biology and Electrostimulation
- Cardiomyopathy and Myosin Studies
- Electrospun Nanofibers in Biomedical Applications
- Mesenchymal stem cell research
- Muscle Physiology and Disorders
- Advanced Fluorescence Microscopy Techniques
University of Bonn
2016-2025
Max Planck Institute for Medical Research
2024
Heidelberg University
2024
University Hospital Heidelberg
2024
Heinrich Heine University Düsseldorf
2024
Düsseldorf University Hospital
2024
Translational Therapeutics (United States)
2024
University of Pennsylvania
2024
Life & Brain (Germany)
2010-2023
University Hospital Bonn
2020
Cellular cardiomyoplasty is an attractive option for the treatment of severe heart failure. It is, however, still unclear and controversial which most promising cell source. Therefore, we investigated examined fate functional impact bone marrow (BM) cells embryonic stem (ES cell)–derived cardiomyocytes after transplantation into infarcted mouse heart. This proved particularly challenging ES cells, as their enrichment long-term engraftment tumorigenicity are poorly understood. We generated...
Ventricular arrhythmias are among the most severe complications of heart disease and can result in sudden cardiac death. Patients at risk currently receive implantable defibrillators that deliver electrical shocks to terminate on demand. However, strong damage cause pain. Therefore, we have tested optogenetic defibrillation using expression light-sensitive channel channelrhodopsin-2 (ChR2) tissue. Epicardial illumination effectively terminated ventricular hearts from transgenic mice WT after...
Oculodentodigital dysplasia (ODDD) is a dominant negatively inherited disorder with variable but characteristic anomalies of the fingers and toes, eyes, face teeth, which are caused by mutations in connexin 43 (Cx43) gene. All analyzed so far have negative influence on conductance through gap junctional channels hemichannels, as well trafficking Cx43 protein transfected cells. In this study, we inserted human Cx43G138R point mutation into mouse gene generated mice conditionally expressing...
Current approaches for the investigation of long-QT syndromes (LQTS) are mainly focused on identification mutation and its characterization in heterologous expression systems. However, it would be extremely helpful to able characterize pathophysiological effects mutations screen drugs cardiomyocytes.The aim this study was establish as a proof principle disease-specific cardiomyocytes from mouse model with LQTS 3 by use induced pluripotent stem (iPS) cells demonstrate that mutant display...
Abstract Optogenetic stimulation allows activation of cells with high spatial and temporal precision. Here we show direct optogenetic skeletal muscle from transgenic mice expressing the light-sensitive channel Channelrhodopsin-2 (ChR2). Largest tetanic contractions are observed 5-ms light pulses at 30 Hz, resulting in 84% maximal force induced by electrical stimulation. We demonstrate utility this approach selectively stimulating a guide individual intralaryngeal muscles explanted larynges...
Optogenetic pacing of the heart has been demonstrated in transgenic animals expressing channelrhodopsin-2 (ChR2). However, for clinical use optogenetics to treat cardiac arrhythmias, gene transfer non-transgenic hearts is required. The aim this study was describe a reliable method ChR2 into sufficient percentage cardiomyocytes overcome electrical sink all coupled non-expressing during optical whole vivo. Adeno-associated virus (AAV) with tropism expression fusion mCherry systemically...
Long QT syndrome is a potentially life-threatening disease characterized by delayed repolarization of cardiomyocytes, interval prolongation in the electrocardiogram, and high risk for sudden cardiac death caused ventricular arrhythmia. The genetic type 3 this (LQT3) gain-of-function mutations SCN5A sodium channel gene which mediates fast Nav1.5 current during action potential initiation. Here, we report analysis LQT3 human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)....
Abstract Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how activity such connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting endogenous G-protein-coupled receptor pathways, can be used modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral...
Directed cardiac differentiation of human pluripotent stem cells (hPSCs) enables disease modeling, investigation cardiogenesis, as well large-scale production cardiomyocytes (CMs) for translational purposes. Multiple CM protocols have been developed to individually address specific requirements these diverse applications, such enhanced purity at a small scale or mass larger scale. However, there is no universal high-efficiency procedure generating CMs both in two-dimensional (2D) and...
The primary goal in the treatment of symptomatic atrial fibrillation/flutter (AF) is to restore sinus rhythm by cardioversion. Electrical shocks are highly effective, but have be applied under analgo-sedation and can further harm heart. In order develop a novel pain-free less harmful approach, we explored herein optogenetic cardioversion light-induced depolarization.Hearts from mice expressing Channelrhodopsin-2 (ChR2) AF-promoting loss-of-function Connexin 40 Ala96Ser mutation were...
Carvedilol is among the most effective β-blockers for improving survival after myocardial infarction. Yet mechanisms by which carvedilol achieves this superior clinical profile are still unclear. Beyond blockade of β1-adrenoceptors, arrestin-biased signalling via β2-adrenoceptors a molecular mechanism proposed to explain benefits. Here, we offer an alternative rationalize carvedilol's cellular signalling. Using primary and immortalized cells genome-edited CRISPR/Cas9 lack either G proteins...
Abstract G q proteins are universally important for signal transduction in mammalian cells. The underlying kinetics and transformation from extracellular stimuli into intracellular signaling, however could not be investigated detail so far. Here we present the human Neuropsin (hOPN5) specific repetitive manipulation of signaling vitro vivo with high spatio-temporal resolution. Properties protein specificity hOPN5 characterized by UV light induced IP 3 generation, Ca 2+ transients inhibition...
Early (E9.5–E11.5) embryonic heart cells beat spontaneously, even though the adult pacemaking mechanisms are not yet fully established. Here we show that in isolated murine early cardiomyocytes periodic oscillations of cytosolic Ca2+ occur and these induce contractions. The originate from sarcoplasmic reticulum dependent on IP3 ryanodine receptor. activate Na+-Ca2+ exchanger, giving rise to subthreshold depolarizations membrane potential and/or action potentials. Although voltage-independent...
Various strategies have been published enabling cardiomyocyte differentiation of human induced pluripotent stem (iPS) cells. However the complex nature signaling pathways involved as well line-to-line variability compromises application a particular protocol to robustly obtain cardiomyocytes from multiple iPS lines. Hence it is necessary identify optimized protocols with alternative combinations specific growth factors and small molecules enhance robustness cardiac differentiation. Here we...
Investigation of Gq signalling with pharmacological agonists Gq-coupled receptors lacks spatio-temporal precision. The aim this study was to establish melanopsin, a light-sensitive receptor, as new tool for the investigation spatial and temporal effects stimulation on pacemaking in cardiomyocytes at an early developmental stage. A vector ubiquitous expression melanopsin tested HEK293FT cells, which showed light-induced production inositol-1,4,5-trisphosphate elevation intracellular Ca2+...
Side effects on cardiac ion channels are one major reason for new drugs to fail during preclinical evaluation. Herein we propose a simple optogenetic screening tool measuring extracellular field potentials (FP) from paced cardiomyocytes identify drug over the whole physiological heart range, which is essential given rate-dependency of channel function and action. Human induced pluripotent stem cell-derived were transduced with an adeno-associated virus express Channelrhodopsin2 plated...
Perlecan is a heparansulfate proteoglycan found in basement membranes, cartilage, and several mesenchymal tissues that form during development, tumour growth, tissue repair. Loss-of-function mutations the perlecan gene mice are associated with embryonic lethality caused primarily by cardiac abnormalities probably due to hemopericards. The aim of present study was investigate mechanism underlying early pathophysiological relevance for heart function. Perlecan-deficient murine stem cells were...