A5060399408- Autoimmune Bullous Skin Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cardiovascular Effects of Exercise
- Urticaria and Related Conditions
- Wnt/β-catenin signaling in development and cancer
- Ocular Surface and Contact Lens
- Skin and Cellular Biology Research
- Cellular Mechanics and Interactions
- Cardiomyopathy and Myosin Studies
- Polysaccharides and Plant Cell Walls
- Cardiac electrophysiology and arrhythmias
- Sports injuries and prevention
- Wound Healing and Treatments
- melanin and skin pigmentation
- Ion channel regulation and function
- HER2/EGFR in Cancer Research
- Nasolacrimal Duct Obstruction Treatments
- Toxin Mechanisms and Immunotoxins
- Cell Adhesion Molecules Research
- Mast cells and histamine
- Hemoglobin structure and function
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Corneal Surgery and Treatments
- Receptor Mechanisms and Signaling
Ludwig-Maximilians-Universität München
2013-2022
LMU Klinikum
2019
Center for Integrated Protein Science Munich
2017
Matrix Research (United States)
2014
In pemphigus vulgaris, a life-threatening autoimmune skin disease, epidermal blisters are caused by autoantibodies primarily targeting desmosomal cadherins desmoglein 3 (DSG3) and DSG1, leading to loss of keratinocyte cohesion. Due limited insights into disease pathogenesis, current therapy relies on nonspecific long-term immunosuppression. Both direct inhibition DSG transinteraction altered intracellular signaling p38 MAPK likely contribute the cell adhesion. Here, we applied tandem peptide...
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...
Adducin is a protein organizing the cortical actin cytoskeleton and target of RhoA PKC signaling. However, role for intercellular cohesion unknown. We found that adducin silencing induced disruption cytoskeleton, reduced adhesion human keratinocytes, decreased levels desmosomal molecule desmoglein (Dsg)3 by reducing its membrane incorporation. Because loss cell Dsg3 depletion observed in autoantibody-mediated blistering skin disease pemphigus vulgaris (PV), we applied antibody fractions PV...
Autoantibodies against desmoglein (Dsg) 1 and Dsg3 primarily cause blister formation in the autoimmune disease pemphigus vulgaris (PV). Src was proposed to contribute loss of keratinocyte cohesion. However, role underlying mechanisms are unclear were studied here. In keratinocytes, cell cohesion response autoantibodies reduced Src-dependent manner by two patient-derived PV-IgG fractions as well AK23 but not a third fraction, although activated all autoantibodies. Loss progredient timeframe...
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...
Meibomian glands within the eyelid are important for maintenance of integrity and health ocular surface. Patients with blistering skin disease pemphigus vulgaris (PV), which is caused by autoantibodies against desmosomal cadherins, often have dry eye disease. Therefore, we studied regulation cell cohesion in human meibomian gland epithelial cells (HMGECs). During serum-induced differentiation 1 to 6 days, HMGECs drastically enhanced intercellular cohesion, whereas lipid production did not...
The autoimmune blistering skin disease pemphigus vulgaris (PV) is caused by autoantibodies against desmosomal adhesion molecules. Patients may suffer conjunctival involvement, yet the underlying mechanisms are largely unclear. We characterized human and murine conjunctiva with respect to PV autoantigens, evaluated effects of applied ex vivo.We obtained specimens from surgical explants established a short-term culture model study alterations induced antibody fractions patients (PV-IgG)....
The meibomian glands (MGs) within the eyelids produce a lipid-rich secretion that forms superficial layer of tear film. Meibomian gland dysfunction (MGD) results in excessive evaporation film, which is leading cause dry eye disease (DED). To develop research model similar to physiological situation MGs, we established new 3D organotypic slice culture (OSC) mouse MGs (mMGs) and investigated effects melanocortins on exocrine secretion. Tissue viability, lipid production morphological changes...
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...
The desmosomal transmembrane adhesion molecule desmoglein 3 (Dsg3) is required for strong keratinocyte cohesion. Recently, we have shown that Dsg3 loss of function, either by siRNA silencing or peptides interfering with binding, increases the activity p38MAPK. In this study, aim to investigate physiological role Dsg3‐dependent p38MAPK suppression. Dsg3‐deficient mice display repetitive skin erosions most which rapidly heal spontaneously. lysates from wound biopsies but also perilesional...
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...
Autoantibodies against desmoglein (Dsg) 1 and Dsg3 primarily cause blister formation in the autoimmune disease pemphigus vulgaris (PV). Src was proposed to contribute loss of keratinocyte cohesion. However, role underlying mechanisms are unclear. In keratinocytes, cell cohesion response autoantibodies reduced a Src‐dependent manner by two patient‐derived PV‐IgG fractions as well AK23, but not third fraction, although activated all autoantibodies. Loss progredient AK23 similar interfered with...