A5020115503- Systemic Lupus Erythematosus Research
- Cytokine Signaling Pathways and Interactions
- Genomics and Chromatin Dynamics
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Circular RNAs in diseases
- MicroRNA in disease regulation
- RNA Research and Splicing
- Rheumatoid Arthritis Research and Therapies
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Extracellular vesicles in disease
- Prion Diseases and Protein Misfolding
- Cholinesterase and Neurodegenerative Diseases
- Cell Adhesion Molecules Research
- Chronic Myeloid Leukemia Treatments
- Cancer-related molecular mechanisms research
- Immunotherapy and Immune Responses
- Genetics and Neurodevelopmental Disorders
- Alzheimer's disease research and treatments
- Immune Cell Function and Interaction
- Chromosomal and Genetic Variations
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
Alexander Fleming Biomedical Sciences Research Center
2015-2024
National and Kapodistrian University of Athens
2015-2019
Synovial fibroblasts (SFs) are specialized cells of the synovium that provide nutrients and lubricants for proper function diarthrodial joints. Recent evidence appreciates contribution SF heterogeneity in arthritic pathologies. However, normal profiles molecular networks govern transition from homeostatic to remain poorly defined.
Complex molecular responses preserve gene expression accuracy and genome integrity in the face of environmental perturbations. Here we report that, response to UV irradiation, RNA polymerase II (RNAPII) molecules are dynamically synchronously released from promoter-proximal regions into elongation promote uniform accelerated surveillance whole transcribed genome. The maximised influx de novo RNAPII correlates with increased damage-sensing, as confirmed by progressive accumulation at...
Abstract Inhibition of transcription caused by DNA damage-impaired RNA polymerase II (Pol II) elongation conceals a local increase in de novo transcription, slowly progressing from Transcription Start Sites (TSSs) to gene ends. Although associated with accelerated repair Pol II-encountered lesions and limited mutagenesis, it is still unclear how this mechanism maintained during genotoxic stress-recovery. Here we uncover widespread gain chromatin accessibility preservation the active H3K27ac...
miRNAs constitute fine-tuners of gene expression and are implicated in a variety diseases spanning from inflammation to cancer. miRNA is deregulated rheumatoid arthritis (RA); however, their specific role key arthritogenic cells such as the synovial fibroblast (SF) remains elusive. Previous studies have shown that Mir221/222 upregulated RA SFs. Here, we demonstrate TNF IL-1β but not IFN-γ activated Mir221 /222 murine SF-specific overexpression huTNFtg mice led further expansion SFs disease...
Abstract In addition to being essential for gene expression, transcription is crucial the maintenance of genome integrity. Here, we undertook a systematic approach, monitor assembly kinetics pre-initiating RNA Polymerase (Pol) II at promoters steady state and different stages during recovery from UV irradiation-stress, when pre-initiation initiation steps have been suggested be transiently shut down. Taking advantage reversible dissociation Pol after high salt treatment, found that de novo...
Amyloid-β protein precursor (AβPP) metabolism and the accumulation of its derivative amyloid-β (Aβ) peptide in senile plaques have been considered key players development Alzheimer's disease (AD). However, mechanisms underlying gene
Abstract The integrity of the actively transcribed genome against helix‐distorting DNA lesions relies on a multilayered cellular response that enhances Transcription‐Coupled Nucleotide Excision Repair (TC‐NER). When defective, TC‐NER is causatively associated with Cockayne‐Syndrome (CS), rare severe human progeroid disorder. Although presence unresolved transcription‐blocking considered driver aging process, molecular features transcription‐driven to genotoxic stress in CS‐B cells remain...
Abstract Synovial fibroblasts (SFs) are specialized cells of the synovium that provide nutrients and lubricants for maintenance proper function diarthrodial joints. Chronic TNF signals known to trigger activation SFs orchestration arthritic pathology via proinflammatory effector functions, secretion cartilage degrading proteases promotion osteolysis. We performed single-cell (sc) profiling SF’s transcriptome by RNA-sequencing (scRNA-seq) chromatin accessibility scATAC-seq in normal mouse...
Abstract MicroRNAs (miRNAs) constitute fine tuners of gene expression and are implicated in a variety diseases spanning from inflammation to cancer. miRNA is deregulated rheumatoid arthritis (RA), however, their specific role key arthritogenic cells such as the synovial fibroblast (SF) remains elusive. We have shown past that miR-221/222 cluster upregulated RA SFs. Here, we demonstrate activation downstream major inflammatory cytokines, TNF IL-1β, which promote independently. SFs huTNFtg...
ABSTRACT Inhibition of RNA synthesis caused by DNA damage-impaired polymerase II (Pol II) elongation is found to conceal a local increase in de novo transcription, slowly progressing from Transcription Start Sites (TSSs) gene ends. Although associated with accelerated repair Pol II-encountered lesions and limited mutagenesis, it still unclear how this mechanism maintained during recovery genotoxic stress. Here we uncover surprising widespread gain chromatin accessibility preservation the...
Background: Our previous studies highlighted the fundamental in vivo role of synovial fibroblasts (SFs) TNF-mediated murine chronic arthritis 1,2 and recent findings identified different SF identities based on their transcriptomic profiles with distinct contributions acute, autoimmunity-based, 3 . Objectives: In this study, we focus delineating map subpopulations healthy joint course arthritic disease underlying regulatory networks functioning towards pathogenicity. Methods: Sorted single...