A5085083689- Mitochondrial Function and Pathology
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Effects of Exercise
- RNA modifications and cancer
- Signaling Pathways in Disease
- Congenital heart defects research
- Listeria monocytogenes in Food Safety
- Genetics and Neurodevelopmental Disorders
- Cardiac Imaging and Diagnostics
- Cardiomyopathy and Myosin Studies
- Nitric Oxide and Endothelin Effects
- Cardiovascular Function and Risk Factors
- RNA Interference and Gene Delivery
- Advanced MRI Techniques and Applications
- Ion channel regulation and function
- Ubiquitin and proteasome pathways
- Electron Spin Resonance Studies
- Microbial Inactivation Methods
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Sports injuries and prevention
- Food Allergy and Anaphylaxis Research
- ATP Synthase and ATPases Research
- Peptidase Inhibition and Analysis
- Cardiac Valve Diseases and Treatments
Universitätsklinikum Würzburg
2015-2025
Comprehensive Cancer Center Mainfranken
2015-2023
Purdue University System
2022
Williams (United States)
2012-2018
University of Würzburg
2005-2016
University Hospital in Halle
2016
German Centre for Cardiovascular Research
2016
Klinikum Brandenburg
2015
Centre National de la Recherche Scientifique
2010
The University of Texas Health Science Center at Houston
1996
Elevated levels of inositol 1,4,5-trisphosphate (IP 3 ) in adult cardiac myocytes are typically associated with the development hypertrophy, arrhythmias, and heart failure. IP enhances intracellular Ca 2+ release via receptors Rs) located at sarcoplasmic reticulum (SR). We aimed to determine whether -induced affects mitochondrial function underlying mechanisms. compared effects Rs- ryanodine (RyRs)-mediated cytosolic elevation achieved by endothelin-1 (ET-1) isoproterenol (ISO) stimulation,...
Nuclear envelope proteins play an important role in the pathogenesis of hereditary cardiomyopathies. Recently, a new form arrhythmic cardiomyopathy caused by homozygous mutation (p.L13R) inner nuclear membrane protein LEMD2 was discovered. The aim to unravel molecular mechanisms mutant cardiomyopathy.We generated Lemd2 p.L13R knock-in mouse model and corresponding cell via CRISPR/Cas9 technology investigated cardiac phenotype as well cellular subcellular rupture repair.Knock-in mice...
Two-component systems are widely distributed in prokaryotes where they control gene expression response to diverse stimuli. To study the role of sixteen putative two-component Listeria monocytogenes systematically, frame deletions were introduced into 15 out 16 regulator genes and resulting mutants characterized. With one exception deletion individual has only minor effects on vitro vivo growth bacteria. The mutant carrying a ortholog Bacillus subtilis degU showed clearly reduced virulence...
Most members of the phylum Firmicutes harbour a two-component system (TCS), LiaSR, which is involved in response to cell envelope stress elicited most notably by inhibitors lipid II cycle. In all LiaSR systems studied detail, LiaSR-mediated signal transduction has been shown be negatively controlled membrane protein, LiaF, encoded upstream liaSR. this study we have analysed orthologue Listeria monocytogenes (LiaSR(Lm)). Whole-genome transcriptional profiling indicated that activation...
We previously demonstrated that conditional overexpression of neuronal nitric oxide synthase (nNOS) inhibited L-type Ca2+ channels and decreased myocardial contractility. However, nNOS has multiple targets within the cardiac myocyte. now hypothesize is cardioprotective after ischemia/reperfusion because inhibition mitochondrial function a reduction in reactive oxygen species generation.Ischemia/reperfusion injury wild-type mice resulted accumulation mitochondria. Similarly, transgenic caused...
Two sons of a consanguineous marriage developed biventricular cardiomyopathy. One boy died severe heart failure at the age 6 years, other was transplanted because 10 years. In addition, focal palmoplantar keratoderma and woolly hair were apparent in both boys. As similar phenotypes have been described Naxos disease Carvajal syndrome, respectively, genes for plakoglobin (JUP) desmoplakin (DSP) screened mutations using direct genomic sequencing. A novel homozygous 2 bp deletion identified an...
Arrhythmogenic cardiomyopathy (AC) is a familial heart disease partly caused by impaired desmosome turnover. Thus, stabilization of integrity may provide new treatment options. Desmosomes, apart from cellular cohesion, the structural framework signaling hub. Here, we investigated role epidermal growth factor receptor (EGFR) in cardiomyocyte cohesion. We inhibited EGFR under physiological and pathophysiological conditions using murine plakoglobin-KO AC model, which was upregulated. inhibition...
Background Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease, which presents with arrhythmias and sudden cardiac death, along progressive remodeling myocardial inflammation. This study aims to elucidate the patterns of [ 18 F]‐fluorodeoxyglucose ([ F]‐FDG) uptake in mouse model plakoglobin‐associated disease better understand its diagnostic potential. Methods Results Plakoglobin ( Jup ) knockout mice developed that presented an ACM‐like phenotype at 6 weeks age. Flow...
Background: Arrhythmogenic cardiomyopathy (ACM) is a genetically inherited desmosome heart disease leading to life-threatening arrhythmias and sudden cardiac death. Currently, ACM treatment paradigms are merely symptom targeting. Recently, apremilast was shown stabilize keratinocyte adhesion in the desmosomal pemphigus vulgaris. Therefore, this study investigated whether can be therapeutic option for ACM. Methods: Human induced pluripotent stem cells from healthy control (hiPSC) an index...
An isogenic mutant of Listeria monocytogenes EGD with a deletion the response regulator gene degU showed lack motility due to absence flagella. In present study, we used two-dimensional gel electrophoresis, mass-spectrometry and microarray analyses identify listerial genes that depend on DegU for expression. We found two L. operons encoding flagella-specific monocistronically transcribed flaA are positively regulated by at 24 degrees C, but not expressed 37 C.
Chronic thromboembolic pulmonary hypertension (CTEPH) is an entity of PH that not only limits patients quality life but also causes significant morbidity and mortality. The treatment choice endarterectomy. However numerous do qualify for endarterectomy or present with residual vasculopathy post require specific vasodilator treatment. Currently, there no available small animal model CTEPH could serve as tool to identify targetable molecular pathways test new options. Thus, we generated...
Abstract Picrosirius red staining constitutes an important and broadly used tool to visualize collagen fibrosis in various tissues. Although multiple qualitative quantitative analysis methods evaluate are available, many require specialized devices software or lack objectivity scalability. Here, we aimed develop a versatile powerful “QuantSeg” macro the FIJI image processing capable of automated, robust, quick quantification cardiac tissue from light micrographs. To examine different...
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....
We demonstrate that in Listeria monocytogenes, temperature-responsive transcriptional control of flagellar genes does not rely on the phosphorylation conserved site (D55) receiver domain response regulator DegU. Furthermore, proper DegU-regulated involved ethanol tolerance and virulence is independent phosphorylation.
E193, a heterozygous truncating mutation in the human transcription cofactor Eyes absent 4 (Eya4), causes hearing impairment followed by dilative cardiomyopathy.In this study, we first show Eya4 and E193 alter expression of p27(kip1) vitro, suggesting is negative regulator p27. Next, generated transgenic mice with cardiac-specific overexpression or E193. Luciferase chromatin immunoprecipitation assays confirmed bind regulate p27 contradictory manner. Activity phosphorylation status...
Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disease caused by heterozygous missense mutations within the gene encoding for nuclear envelope protein transmembrane 43 (TMEM43). The characterized myocyte loss and fibro-fatty replacement, leading to life-threatening ventricular arrhythmias sudden cardiac death. However, role of TMEM43 in pathogenesis ACM remains poorly understood. In this study, we generated cardiomyocyte-restricted transgenic zebrafish lines that...
Purpose A method for the quantification of perfusion in murine myocardium is demonstrated. The allows reconstruction maps on arbitrary time points heart cycle while addressing problems that arise due to irregular beat mice. Methods flow-sensitive alternating inversion recovery arterial spin labeling using an untriggered FLASH-read out with random sampling used. Look-Locker conditions are strictly maintained. No dummy pulses or mechanism reduce deviation from needed. Electrocardiogram and...
Abstract The objective of this study was to identify unknown modulators Calcineurin (Cn)-NFAT signaling. Measurement NFAT reporter driven luciferase activity therefore utilized screen a human cardiac cDNA-library (~10 7 primary clones) in C2C12 cells through serial dilutions until single clones could be identified. This extensive screening strategy culminated the identification SUMO2 as most efficient Cn-NFAT activator. SUMO2-mediated activation signaling cardiomyocytes translated into...
Recent evidence demonstrated that alterations in the QT interval duration on ECG are not only determined by mutations genes for ion channels, but also modulators of channels. Changes beyond certain thresholds pathological and can lead to sudden cardiac death. We here focus channel modulator nitric oxide synthase 1 adaptor protein (Nos1ap). Whole-cell patch-clamp measurements a conditional transgenic mouse model exhibiting cardiac-specific Nos1ap over-expression revealed Nos1ap-dependent...