A5001429864- Cardiovascular Effects of Exercise
- Cardiac electrophysiology and arrhythmias
- Skin and Cellular Biology Research
- Sports injuries and prevention
- Receptor Mechanisms and Signaling
- Cardiomyopathy and Myosin Studies
- Cellular Mechanics and Interactions
- Wnt/β-catenin signaling in development and cancer
- Neuroscience and Neural Engineering
- Autoimmune Bullous Skin Diseases
- Plant Reproductive Biology
- Glycosylation and Glycoproteins Research
- Ion channel regulation and function
- Cell Adhesion Molecules Research
- Cardiac Arrest and Resuscitation
- Hair Growth and Disorders
- Integrated Circuits and Semiconductor Failure Analysis
- Food Allergy and Anaphylaxis Research
- Cancer, Stress, Anesthesia, and Immune Response
- Eosinophilic Disorders and Syndromes
- Marine Biology and Environmental Chemistry
- Vascular Tumors and Angiosarcomas
- Heart Rate Variability and Autonomic Control
- Genetics and Physical Performance
- Cardiac Fibrosis and Remodeling
University Cancer Center Hamburg
2025
University Medical Center Hamburg-Eppendorf
2025
Universität Hamburg
2025
University Hospital of Bern
2025
University of Bern
2025
University of Basel
2018-2024
Medizinische Hochschule Hannover
2022-2024
Ludwig-Maximilians-Universität München
2014-2020
LMU Klinikum
2018
Institute of Pathology Celle
2017
In vitro models incorporating the complexity and function of adult human tissues are highly desired for translational research. Whilst vital slices myocardium approach these demands, their rapid degeneration in tissue culture precludes long-term experimentation. Here, we report preservation structure performance under conditions physiological preload, compliance, continuous excitation. biomimetic culture, prepared from explanted failing hearts attain a stable state contractility that can be...
We determined the contribution of desmosomal cadherin desmoglein-2 to cell-cell cohesion in cardiomyocytes. In intercalated disc, providing mechanical strength and electrical communication between adjacent cardiomyocytes, is closely associated with N-cadherin gap junctions.We studied discs HL-1 cardiomyocytes by immunostaining N-cadherin. Cohesion was measured using a liberase-based dissociation-assay compared cell-free single-molecule atomic force microscopy measurements. L-tryptophan...
The sympathetic nervous system is a major mediator of heart function. Intercalated discs composed desmosomes, adherens junctions, and gap junctions provide the structural backbone for coordinated contraction cardiac myocytes.Gap dynamically remodel to adapt signaling. However, it unknown whether such rapid adaption also occurs adhesive function provided by desmosomes junctions.Atomic force microscopy revealed that β-adrenergic signaling enhances both number desmoglein 2-specific interactions...
Arrhythmogenic cardiomyopathy (ACM) is characterized by progressive loss of cardiomyocytes with fibrofatty tissue replacement, systolic dysfunction, and life-threatening arrhythmias. A substantial proportion ACM caused mutations in genes the desmosomal cell-cell adhesion complex, but underlying mechanisms are not well understood. In current study, we investigated relevance defective for development progression.We mutated binding site DSG2 (desmoglein-2), a crucial molecule cardiomyocytes....
Glycosylation is essential to facilitate cell–cell adhesion and differentiation. We determined the role of dolichol phosphate mannosyltransferase (DPM) complex, a central regulator for glycosylation, desmosomal adhesive function epidermal Deletion key molecule DPM DPM1, in human keratinocytes resulted weakened adhesion, impaired localization components desmoplakin desmoglein-2, led cytoskeletal organization defects keratinocytes. In 3D organotypic epidermis model, loss DPM1 caused...
Desmosomes are adhesive cell contacts abundant in tissues exposed to mechanical strain, such as the stratified and simple epithelia of epidermis mucous membranes, well myocardium. Besides their role cohesion, desmosomes also modulate pathways important for tissue differentiation, wound healing immune responses. Dysfunctional desmosomes, resulting from pathogenic variants genes encoding desmosomal components, autoantibodies targeting adhesion molecules or inflammation, cause life-threatening...
Background: Arrhythmogenic Cardiomyopathy (ACM) is one of the major causes sudden cardiac death in young adults. With underlying patho-mechanisms not well understood, current therapeutic approaches for this genetic disease are solely symptomatic. A recent study demonstrates that loss cell-cell adhesion an important initial step leading to ACM. Because considered a key step, we aim identify new compounds from drug library, which can restore intercellular and potentially serve as therapeutics...
The adhesion G protein–coupled receptor (aGPCR) GPR126/ADGRG6 plays an important role in several physiological functions, such as myelination or peripheral nerve repair. This renders the attractive pharmacological target. GPR126 is a mechano-sensor that translates binding of extracellular matrix (ECM) molecules to its N terminus into metabotropic intracellular signal. To date, structural requirements and character forces needed for this ECM-mediated activation are largely unknown. In study,...
Arrhythmogenic cardiomyopathy (AC) is a genetic disease causing arrhythmia and sudden cardiac death with only symptomatic therapy available at present. Mutations of desmosomal proteins, including desmoglein-2 (Dsg2) plakoglobin (Pg), are the major cause AC have been shown to lead impaired gap junction function. Recent data indicated involvement anti-Dsg2 autoantibodies in pathogenesis. We applied peptide stabilize Dsg2 binding similar translational approach pemphigus, which caused by...
Arrhythmogenic cardiomyopathy (AC) is a heart disease often caused by mutations in genes coding for desmosomal proteins, including desmoglein-2 (DSG2), plakoglobin (PG), and desmoplakin (DP). Therapy based on symptoms limiting arrhythmia, because the mechanisms which components control cardiomyocyte function are largely unknown. A new paradigm could be to stabilize adhesion hyperadhesion, renders independent from Ca2+. Here, we further characterized behind enhanced hyperadhesion....
Abstract Desmosomal proteins are components of the intercalated disc and mediate cardiac myocyte adhesion. Enhancement cohesion, referred to as “positive adhesiotropy”, was demonstrated be a function sympathetic signaling relevant for sufficient inotropic response. We used agent digitoxin investigate link between inotropy adhesiotropy. In contrast wild-type hearts, failed enhance pulse pressure in perfused mice hearts lacking desmosomal protein plakoglobin which paralleled with abrogation...
Desmoplakin (Dp) is a crucial component of the desmosome, supramolecular cell junction complex anchoring intermediate filaments. The mechanisms how Dp modulates cell-cell adhesion are only partially understood. Here, we studied impact on function desmosomal molecules, desmosome turnover and intercellular adhesion.CRISPR/Cas9 was used for gene editing human keratinocytes which were characterized by Western blot immunostaining. Desmosomal ultrastructure assessed electron microscopy assays....
Pemphigus vulgaris (PV) is a potentially lethal autoimmune disease characterized by blister formation of the skin and mucous membranes caused autoantibodies against desmoglein (Dsg) 1 Dsg3. Dsg1 Dsg3 are linked to keratin filaments in desmosomes, adhering junctions abundant tissues exposed high levels mechanical stress. The binding leads internalization collapse cytoskeleton – yet, relevance interdependence these changes for loss cell-cell adhesion blistering poorly understood. In live-cell...
Abstract Aims Mutations in desmosomal proteins can induce arrhythmogenic cardiomyopathy with life‐threatening arrhythmia. Previous data demonstrated adrenergic signalling to be important regulate cohesion cardiac myocytes. Here, we investigated how pathways including signalling, PKC and SERCA adhesion this controls gap junctions (GJs) Methods Immunostaining, Western blot, dissociation assay multi‐electrode array were applied HL‐1 myocytes evaluate localization, expression function of GJ...
Desmosomes are intercellular adhesion complexes providing mechanical coupling and tissue integrity. Previously, a correlation of desmosomal molecule expression with invasion metastasis formation in several tumor entities was described together relevance for circulating cell cluster formation. Here, we investigated the contribution core desmoglein-2 (DSG2) to initial steps liver by pancreatic cancer cells using novel ex vivo perfusion mouse model. We applied ductal adenocarcinoma line AsPC-1...
Intercellular adhesion is essential for tissue integrity and homeostasis. Desmosomes are especially abundant in the epidermis myocardium, tissues, which under constantly changing mechanical stresses. Yet, it largely unclear whether desmosomal can be rapidly adapted to demands mechanisms underlying desmosome turnover only partially understood. We here show that loss of actin-binding protein α-adducin prevented ability cultured keratinocytes or murine withstand stress paralleled with reduced...
Abstract The adhesion G protein-coupled receptor (aGPCR) GPR126/ADGRG6 plays an important role in several physiological functions, such as myelination or peripheral nerve repair. This renders the attractive pharmacological target. GPR126 is a mechano-sensor that translates binding of extracellular matrix (ECM) molecules to its N terminus into metabotropic intracellular signal. To date, structural requirements and character forces needed for this ECM-mediated activation are largely unknown....
ABSTRACT Desmoplakin (Dp) localizes to desmosomes, linking clusters of desmosomal adhesion molecules the intermediate filament cytoskeleton. Here, we generated Dp knockout (ko) cell lines human keratinocytes study impact on and desmosome turnover using atomic force microscopy superresolution imaging. In comparison ko another component, plakoglobin (Pg), loss resulted in absence desmosomes drastically impaired cohesion. ko, desmoglein 2 (Dsg2) desmocollin 3 (Dsc3) were redistributed into...
ABSTRACT Glycosylation is essential to facilitate cell-cell adhesion and differentiation. We determined the role of dolichol phosphate mannosyltransferase (DPM) complex, a central regulator for glycosylation, desmosomal adhesive function epidermal Deletion key molecule DPM DPM1, in human keratinocytes resulted weakened adhesion, impaired localization components desmoplakin desmoglein-2, led cytoskeletal organization defects keratinocytes. In 3D organotypic epidermis model, loss DPM1 caused...
Cardiomyocytes are electrically and mechanically coupled via intercalated discs (ICDs) composed of desmosomes, adherens junctions gap junctions. The desmosomal cadherins desmoglein 2 (Dsg2) desmocollin the classical cadherin N‐cadherin transmembrane adhesion molecules ICD provide intercellular adhesive strength. Gap dynamically remodel to adapt cyclic adenosine 5′‐monophosphate (cAMP) signaling. It is unknown whether such rapid adaption also evident for function ICD. Atomic force microscopy...
The intercalated disc (ICD), composed of desmosomes, adherens junctions and gap junctions, provides the structural backbone for coordinated contraction integrity heart. Recently we have reported sympathetic signaling to regulate cell cohesion cardiomyocytes. Increased cAMP levels strengthened desmoglein 2 (Dsg2)‐mediated adhesion paralleled with a reorganization ICD. Here demonstrate this adrenergic effect be strictly dependent on plaque protein plakoglobin (Pg). Similar Dsg2, Pg staining...
Defective cell-cell adhesion contributes to the patho-mechanism of various diseases. In line with this, a mouse model recently developed by our group demonstrate that loss is an important initial step leading Arrhythmogenic Cardiomyopathy (ACM), disease which presents severe arrhythmia, ventricular fibrosis and impaired cardiac function. Derived from central role defective for patho-mechanism, we here aim identify new compounds, restore intercellular could serve as potential therapeutics. To...
Arrhythmogenic Cardiomyopathy (ACM) is characterized by progressive loss of cardiomyocytes with fibrosis, systolic dysfunction and life-threatening arrhythmias. Mutations in genes the desmosomal adhesion complex such as desmoglein-2 (Dsg2) are major cause, but underlying mechanisms leading to disease not well understood. Accordingly, only symptomatic treatment available. Here, we establish an inducible Dsg2-W2A knock-in mouse model temporal control onset new approach analyse early processes...