A5044157623- Cardiomyopathy and Myosin Studies
- RNA Interference and Gene Delivery
- Congenital heart defects research
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Cardiovascular Effects of Exercise
- Viral Infections and Immunology Research
- Neonatal Respiratory Health Research
- Extracellular vesicles in disease
- Cardiovascular Function and Risk Factors
- Immune Response and Inflammation
- Cardiac electrophysiology and arrhythmias
- Cancer-related molecular mechanisms research
- Protein Degradation and Inhibitors
- Atrial Fibrillation Management and Outcomes
- Congenital Heart Disease Studies
- Circadian rhythm and melatonin
- Proteoglycans and glycosaminoglycans research
- Cardiac Arrhythmias and Treatments
- Cardiac Fibrosis and Remodeling
- CRISPR and Genetic Engineering
- Histone Deacetylase Inhibitors Research
- Animal Genetics and Reproduction
- Respiratory viral infections research
Charité - Universitätsmedizin Berlin
2017-2025
German Center for Lung Research
2024-2025
Thomas Jefferson University
2021-2024
German Centre for Cardiovascular Research
2019-2024
Czech Academy of Sciences, Institute of Physiology
2024
Max Delbrück Center
2017-2021
Deutsches Herzzentrum München
2019-2021
Deutsches Herzzentrum der Charité
2019-2021
Humboldt-Universität zu Berlin
2019
Freie Universität Berlin
2019
Myocarditis is one of the most common causes leading to heart failure in children and a possible genetic background has been postulated. We sought characterize clinical characteristics patients with myocarditis ≤18 years age predict outcome.A cohort 42 (Genetics Pediatric Myocarditis) biopsy-proven underwent testing targeted panel sequencing cardiomyopathy-associated genes. Genetics were divided into subgroups according phenotype dilated cardiomyopathy (DCM) at presentation, resulting 22...
Significance Circadian (24-h) rhythms influence the behavior and physiology of many organisms. These are generated at gene expression level, causing waxing waning protein abundances. Metabolic enzymes affected, but principles for propagation enzyme rhythmicity to cellular metabolism as quantified by fluxes through metabolic pathways metabolite concentrations not understood. We used mathematics chemical kinetics systematically investigate how in activity propagated pathway concentrations. It...
Nucleoside modified mRNA combined with Acuitas Therapeutics’ lipid nanoparticles (LNPs) has been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later humans the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due LNPs’ ionizable component. The property key development of potent responses. However, mechanism by which drives T follicular helper (Tfh) cells remains unknown. Here we show lack Langerhans or...
Hundreds of millions SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding the immune effects this platform. The mRNA-LNP-based is highly inflammatory, and its synthetic ionizable lipid component responsible for induction inflammation has long in vivo half-life. Since chronic can lead exhaustion non-responsiveness, sought determine pre-exposure on adaptive responses innate fitness. We found that mRNA-LNPs or LNP alone led...
Glycosylated RNA (glycoRNA) has recently emerged as a novel constituent of the glycocalyx on cell surfaces, yet its biological functions remain largely unexplored. In this report, we present first analysis glycoRNA expression and functionality in alveolar epithelial cells. To end, optimized new techniques for detection living surfaces membrane-associated samples through in-gel imaging after labeling with fluorescent dye conjugates. Specifically, used conjugation Cy5-hydrazide following mild...
Abstract The underlying genetic mechanisms and early pathological events of children with primary cardiomyopathy (CMP) are insufficiently characterized. In this study, we aimed to characterize the mutational spectrum CMP in a large cohort patients ≤18 years referred tertiary center. Eighty unrelated index pediatric underwent testing panel‐based next‐generation sequencing approach 89 genes. At least one pathogenic or probably variant was identified 30/80 (38%) patients. all subgroups, carried...
Background Cardiomyopathies are heterogeneous diseases with clinical presentations varying from asymptomatic to life‐threatening events, including severe heart failure and sudden cardiac death. The role of underlying genetic disease‐modulating factors in children adolescents is relatively unknown. In this prospective study, in‐depth phenotypic characterization pediatric patients primary cardiomyopathy their first‐degree family members (FMs) was performed. Outcome assessed identify risk...
Bromodomain protein 4 (BRD4), a member of the bromodomain and extra-terminal (BET) family, acts as central element in transcriptional elongation plays essential roles cell proliferation. Inhibition BRD4 binding to acetylated histone tails via its two bromodomains, BD1 BD2, with small-molecule inhibitors has been shown be valid strategy prevent cancer growth. We have evaluated established novel assays that quantify interaction transfected chemical inside cultured cells. Both methods are based...
In vitro lung research requires appropriate cell culture models that adequately mimic in vivo structure and function. Previously, researchers have extensively utilized commercially available easily expandable A549 NCI-H441 cells which replicate some yet not all features of alveolar epithelial cells. Specifically, these are often restricted by terminally altered expression while lacking important characteristics. Of late, human primary (hPAEpC) become available, but so far poorly specified....
Background: Left ventricular noncompaction cardiomyopathy (LVNC CMP) is a genetic cardiomyopathy. Genotype-phenotype correlation and clinical outcome of variants in pediatric adult LVNC CMP patients are still unclear. Methods: The retrospective multicenter study was conducted unrelated index with CMP, diagnosed between the years 1987 2017, all available family members. All underwent next-generation sequencing for 174 target genes using Illumina TruSight Cardio Sequencing Panel. Major adverse...
Abstract Glycosylated RNA (glycoRNA) has recently emerged as a novel constituent of the glycocalyx on cell surfaces, yet its biological functions remain largely unexplored. In this report, we present first analysis glycoRNA expression and functionality in alveolar epithelial cells. To end, optimized new techniques for detection living surfaces membrane-associated samples through in-gel imaging after labeling with fluorescent dye conjugates. Specifically, used conjugation Cy5-hydrazide...
Hundreds of millions SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding the immune effects this platform. The mRNA-LNP-based is highly inflammatory, and its synthetic ionizable lipid component responsible for induction inflammation has long in vivo half-life. Since chronic can lead exhaustion non-responsiveness, sought determine pre-exposure on adaptive responses innate fitness. We found that mRNA-LNPs or LNP alone led...
Dendritic cells (DCs) are required for the initiation of adaptive immune response. Their ability to acquire antigens in periphery is a critical step this process. DCs express wide variety adhesion molecules and possess an extremely fluid plasma membrane that facilitates scavenging extracellular environment capturing material like exosomes, apoptotic bodies, pathogens. Besides these standard routes, acquisition by can be further facilitated tunneling nanotubes, trogocytosis, gap junctions....
Sialylated glycans such as sialoglycoproteins, sialoglycolipids and sialoglycoRNA are ubiquitous in the glycocalyx of cells where they play a key role barrier function, mechanosensation, infection, immune cell traffcking, inflammation. These functions particularly relevant at blood-gas lung. The alveolar epithelial is furthermore unique that it constantly exposed to cyclic stretch because normal breathing. Yet, abundance, regulation function sialylated remains unknown. Here, we focused on...
Nucleoside modified mRNA combined with Acuitas Therapeutics' lipid nanoparticles (LNP) have been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later humans the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due LNPs' ionizable component. The property key development of potent responses. However, mechanism by which drives T follicular helper cells (Tfh) remains unknown. Here we show lack Langerhans or...
Abstract During the ongoing SARS-CoV-2 pandemic, hundreds of millions people have been exposed to experimental mRNA-LNP-based COVID vaccines, which long-term immune effects are unknown. We previously showed that this vaccine platform is highly inflammatory. Its synthetic ionizable lipid component, has a long in vivohalf-life, responsible for induction inflammation and adaptive responses. The inflammatory component’s vivohalf-life could be reminiscence chronic infection, known lead exhaustion...
Objectives: Pediatric heart failure is a severe, life-threatening condition that may result from genetically determined cardiomyopathy. Although the mechanisms leading to cardiomyopathy are well-established in adults, underlying genetic mechanisms, early pathological events and further disease promoting factors poorly characterized children. To overcome this limitation RIKADA study explores clinical presentation, biochemical environment, status of index-patients their first-degree relatives in-depth.
Background: Idiopathic ventricular fibrillation (VF) is a rare disease often leading to sudden cardiac death (SCD). Therapeutic options are limited although successful ablation procedures which target VF triggering premature complexes (PVC) have been reported. Here we present case where combined ablative strategy was in preventing further VF.
Cardiomyopathy in pediatric patients is life-threatening and may result from genetic defects. While well established adults, mechanisms, early pathological events, other disease promoting factors are poorly characterized children. Recently, we identified pathogenic variants the gene PR/SET domain 16 (PRDM16) underlying isolated cardiomyopathy with nonsyndromic left ventricular noncompaction (LVNC).
Objectives: Cardiomyopathies (CMPs) are heterogeneous diseases with clinical presentation varying from asymptomatic to severe heart failure. The role of underlying genetic and disease modulating factors in children adolescents is relatively unknown. This study sought perform in-depth characterization pediatric CMP patients first-degree family members (FMs) as well assess outcome aiming contribute risk stratification.