A5004454019- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Autophagy in Disease and Therapy
- Pluripotent Stem Cells Research
- Neonatal Respiratory Health Research
- Cancer Immunotherapy and Biomarkers
- Acute Myeloid Leukemia Research
- Kruppel-like factors research
- Cardiovascular Function and Risk Factors
- Mitochondrial Function and Pathology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Congenital Diaphragmatic Hernia Studies
- Immune cells in cancer
- Adipose Tissue and Metabolism
- Genetics and Neurodevelopmental Disorders
- Cell Adhesion Molecules Research
- Genomics and Rare Diseases
- FOXO transcription factor regulation
- Fibroblast Growth Factor Research
- Histone Deacetylase Inhibitors Research
- Invertebrate Immune Response Mechanisms
- Lysosomal Storage Disorders Research
- Inflammasome and immune disorders
- Telomeres, Telomerase, and Senescence
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2024-2025
University of Cologne
2018-2025
University Hospital Cologne
2020-2025
National Centre of Scientific Research "Demokritos"
2009
Innate immunity triggers responsible for viral control or hyperinflammation in COVID-19 are largely unknown. Here we show that the SARS-CoV-2 spike protein (S-protein) primes inflammasome formation and release of mature interleukin-1β (IL-1β) macrophages derived from patients but not healthy naïve individuals. Furthermore, longitudinal analyses reveal robust S-protein-driven activation isolated convalescent patients, which correlates with distinct epigenetic gene expression signatures...
Abstract Dysfunctions in autophagy, a cellular mechanism for breaking down components within lysosomes, often lead to neurodegeneration. The specific mechanisms underlying neuronal vulnerability due autophagy dysfunction remain elusive. Here we show that contributes cerebellar Purkinje cell (PC) survival by safeguarding their glycolytic activity. Outside the conventional housekeeping role, is also involved ATG5-mediated regulation of glucose transporter 2 (GLUT2) levels during maturation....
Abstract Culture expansion of primary cells evokes highly reproducible DNA methylation (DNAm) changes. We have identified CG dinucleotides (CpGs) that become continuously hyper- or hypomethylated during long-term culture mesenchymal stem (MSCs) and other cell types. Bisulfite barcoded amplicon sequencing (BBA-seq) demonstrated DNAm patterns neighboring CpGs more complex without evidence continuous pattern development association to oligoclonal subpopulations. Circularized chromatin...
Obesity is a pre-disposing condition for chronic obstructive pulmonary disease, asthma, and arterial hypertension. Accumulating evidence suggests that metabolic influences during development can determine lung diseases (CLD). We demonstrate maternal obesity causes early disorder in the offspring. Here, interleukin-6 induced bronchial microvascular smooth muscle cell (SMC) hyperproliferation increased airway vascular resistance. The key anti-proliferative transcription factor FoxO1 was...
Objective: Nonalcoholic fatty liver disease (NAFLD) ranges from steatosis to nonalcoholic steatohepatitis (NASH), which often progresses hepatocellular carcinoma (HCC) through a largely undefined mechanism.NASH and HCC depend on inflammatory signaling, whose master regulator is the NFkB transcription factor family, activated by canonical non-canonical pathways.Methods: Here, we investigated NFkB-inducing kinase (NIK/MAP3K14) in metabolic NASH, NASH transition, DENinduced HCC.To this end,...
Myeloperoxidase (MPO) is an enzyme that functions in host defense. MPO released into the vascular lumen by neutrophils during inflammation and may adhere subsequently penetrate endothelial cells (ECs) coating walls. We show enters nucleus of ECs binds chromatin independently its enzymatic activity. drives decondensation at binding sites enhances condensation neighboring regions. It loci relevant for endothelial-to-mesenchymal transition (EndMT) affects migratory potential ECs. Finally,...
Abstract Dysfunctions in autophagy, a highly conserved cellular mechanism responsible for the degradation of intracellular components within lysosomes, often result neurodegeneration. The neuroprotective effect autophagy varies across neuronal subtypes, and mechanisms selective vulnerability neurons to dysfunction are currently unknown. Utilizing mouse model ATG5 deficiency inhibitory comprehensive approach, including PET imaging, metabolomics, stable-isotope labeling studies, live cell we...
Abstract Culture expansion of primary cells evokes highly reproducible DNA methylation (DNAm) changes at specific sites in the genome. These might be due to an directly regulated epigenetic process, or gradual deregulation state, which is often referred as “epigenetic drift”. We have identified CG dinucleotides (CpGs) that become continuously hyper- hypomethylated course culture mesenchymal stem (MSCs) and other cell types. During reprogramming into induced pluripotent (iPSCs) particularly...
Replicative senescence of cells is associated with reproducible DNA methylation (DNAm) changes at specific sites in the genome. We have identified CG dinucleotides (CpGs) that become continuously hyper- or hypomethylated upon culture expansion mesenchymal stem and other cell types. During reprogramming into induced pluripotent cells, senescence-associated DNAm reversed simultaneously pluripotency-associated changes. Bisulfite barcoded amplicon sequencing (BBA-seq) demonstrated passaging...
Abstract Dysfunctions in autophagy, a cellular mechanism for breaking down components within lysosomes, often lead to neurodegeneration. The specific mechanisms underlying neuronal vulnerability autophagy dysfunction remain elusive. Here, we show that contributes the survival of cerebellar Purkinje cells (PCs) by safeguarding their glycolytic activity. This function is independent its conventional housekeeping role and involves ATG5-mediated regulation glucose transporter 2 (GLUT2) levels...
Neurodevelopmental disorders exhibit clinical and genetic heterogeneity, ergo manifest dysfunction in components of diverse cellular pathways; the precise pathomechanism for majority remains elusive.
Abstract As a subterranean eusocial mammal, the naked mole-rat faces particularly challenging environment characterised by patchily available food, low O 2 and high CO levels. In response, mole-rats have evolved suite of molecular physiological adaptations to survive extreme hypoxia. Yet, how rewire their metabolism protect heart has not been comprehensively addressed. Here, we performed comparative analyses mouse organs exposed ischaemic conditions. We show that retained features foetal...
<b>Rationale:</b> Supplementary oxygen leads to bronchopulmonary dysplasia (BPD) in preterm infants, a disease characterized by lung growth arrest and matrix remodeling. We demonstrated that hyperoxia reduces Krüppel-like factor 4 (Klf4), key transcription cell biology. Since myofibroblasts are crucial injury remodeling, we investigated the functional role of Klf4 pathogenesis BPD homeostasis fibroblasts. <b>Methods:</b> (1) Newborn C57BL/6N mice were exposed 85% O2 (HYX) or 21% (NOX) until...
<b>Background:</b> Obesity contributes to lung diseases and regeneration. Prior studies from our group showed that perinatal maternal obesity induces bronchial vascular remodeling in later life. However, the impact of on alveolarization alveolar regenerative niche remains uncertain. <b>Aims:</b> (1) To investigate formation epithelial type II cells (ATII) as progenitor cells; (2) study effect white adipose tissue (WAT) its adipocytokines ATII. <b>Methods:</b> 1) Female mice were fed with...
ABSTRACT Myeloperoxidase (MPO) is an enzyme that functions in host defence by catalysing the formation of reactive oxygen intermediates. Synthesized majorly myeloid progenitor cell types and neutrophils, MPO released into vascular lumen during inflammation, where it may adhere subsequently enter endothelial cells coating walls. Here, we show actually enters nucleus these binds chromatin independently its enzymatic activity to cause changes structure. At binding sites, drives decondensation,...