A5044019383- Nuclear Structure and Function
- RNA Research and Splicing
- Genetic and Kidney Cyst Diseases
- Cellular Mechanics and Interactions
- Hippo pathway signaling and YAP/TAZ
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- Cardiovascular Effects of Exercise
- Skin and Cellular Biology Research
- Heat shock proteins research
- RNA modifications and cancer
- Protist diversity and phylogeny
- Cystic Fibrosis Research Advances
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- Micro and Nano Robotics
- Melanoma and MAPK Pathways
- Polyamine Metabolism and Applications
- Biotin and Related Studies
- Lymphatic System and Diseases
- Cardiac Fibrosis and Remodeling
- Connective Tissue Growth Factor Research
- Biomedical Research and Pathophysiology
- Nanocluster Synthesis and Applications
- Muscle Physiology and Disorders
University of Cyprus
2022-2025
University of Oxford
2018-2025
Inserm
2014-2022
Centre de Recherche en Myologie
2014-2022
Institut de Myologie
2014-2021
Sorbonne Université
2014-2021
Université Paris Cité
2018
Pitié-Salpêtrière Hospital
2016
Hull York Medical School
2016
University of York
2016
Article27 May 2019Open Access Source Data RASSF1A controls tissue stiffness and cancer stem-like cells in lung adenocarcinoma Daniela Pankova Department of Oncology, University Oxford, UK Search for more papers by this author Yanyan Jiang Oxford Institute Radiation Maria Chatzifrangkeskou orcid.org/0000-0003-3703-491X Iolanda Vendrell TDI Mass Spectrometry Laboratory, Nuffield Medicine, Target Discovery Jon Buzzelli Anderson Ryan Cameron Brown School Chemistry, Physics Mechanical...
Cardiomyopathy caused by lamin A/C gene mutations ( LMNA cardiomyopathy) is characterized increased myocardial fibrosis, which impairs left ventricular relaxation and predisposes to heart failure, cardiac conduction abnormalities. While we previously discovered abnormally elevated extracellular signal-regulated kinase 1/2 (ERK1/2) activities in cardiomyopathy, its role on the development of fibrosis remains unclear. We now showed that transforming growth factor (TGF)-β/Smad signaling...
Abstract Mutations in the lamin A/C gene ( LMNA ) cause dilated cardiomyopathy associated with increased activity of ERK1/2 heart. We recently showed that phosphorylates cofilin-1 on threonine 25 (phospho(T25)-cofilin-1) turn disassembles actin cytoskeleton. Here, we show muscle cells carrying a cardiomyopathy-causing mutation, phospho(T25)-cofilin-1 binds to myocardin-related transcription factor A (MRTF-A) cytoplasm, thus preventing stimulation serum response (SRF) nucleus. Inhibiting...
Hyper-activation of extracellular signal-regulated kinase (ERK) 1/2 contributes to heart dysfunction in cardiomyopathy caused by mutations the lamin A/C gene (LMNA cardiomyopathy). The mechanism how this affects cardiac function is unknown. We show that active phosphorylated ERK1/2 directly binds and catalyzes phosphorylation actin depolymerizing factor cofilin-1 on Thr25. Cofilin-1 becomes disassembles filaments a large array cellular animal models LMNA cardiomyopathy. In vivo expression...
Cardiomyopathy caused by lamin A/C gene (LMNA) mutations (hereafter referred as LMNA cardiomyopathy) is an anatomic and pathologic condition associated with muscle electrical dysfunction of the heart, often leading to heart failure-related disability. There currently no specific therapy available for patients that target molecular pathophysiology cardiomyopathy. Recent studies suggested nicotinamide adenine dinucleotide (NAD+) cellular content could be a critical determinant function....
Article7 June 2019Open Access Source DataTransparent process RASSF1A is required for the maintenance of nuclear actin levels Maria Chatzifrangkeskou orcid.org/0000-0003-3703-491X Department Oncology, University Oxford, UK Search more papers by this author Dafni-Eleftheria Pefani orcid.org/0000-0002-1956-5111 Laboratory Biology, Medical School, National and Kapodistrian Athens, Greece Biomedical Research Foundation Academy Michael Eyres Iolanda Vendrell Nuffield Medicine, Target Discovery...
Mutations in the lamin A/C gene (LMNA) cause an autosomal dominant inherited form of dilated cardiomyopathy associated with cardiac conduction disease (hereafter referred to as LMNA cardiomyopathy). Compared other forms cardiomyopathy, mutations are responsible for a more aggressive clinical course owing high rate malignant ventricular arrhythmias. Gap junctions intercellular channels that allow direct communication between neighboring cells, which involved electrical impulse propagation and...
The mechanical environment is sensed through cell-matrix contacts with the cytoskeleton, but how signals transit nuclear envelope to affect cell fate decisions remains unknown. Nuclear actin coordinates chromatin motility during differentiation and genome maintenance, yet it unclear responds force. DNA-damage kinase ataxia telangiectasia Rad3-related protein (ATR) translocates protect nucleus or compression. Here, we show that ATR drives assembly via recruitment of Filamin-A inner membrane...
Motile cilia play essential roles in various physiological processes including fluid flow generation and sperm motility. In this study, we identified 1,3-diphenyl-6-(4-phenylpiperazin-1-yl)benzo[e][1,2,4]triazin-7(1H)-one as a potent reversible modulator of ciliary function using the Xenopus laevis model. This benzotriazinone derivative inhibits ciliary-driven by inducing detachment without causing toxicity developing embryos. Unlike traditional deciliation agents that rely on calcium...
MicroRNAs (miRNAs) are short non-coding RNAs that silence mRNAs. They generated following transcription and cleavage by the DROSHA/DGCR8 DICER/TRBP/PACT complexes. Although it is known components of miRNA biogenesis machinery can be phosphorylated, remains poorly understood how these events become engaged during physiological cellular activation. We demonstrate S6 kinases phosphorylate extended C-terminal domain TRBP interact with in situ primary cells. serines 283/286 essential for...
The c-Jun N-terminal kinase (JNK) regulates various important physiological processes. Although the JNK pathway has been under intense investigation for over 20 yr, its complexity is still perplexing, with multiple protein partners underlying diversity of activity. We show that associated basal bodies in both primary and motile cilia. Loss disrupts body migration docking leads to severe ciliogenesis defects. JNK’s involvement stems from a dual role regulation actin networks multiciliated...
Cofilins are important for the regulation of actin cytoskeleton, sarcomere organization, and force production. The role cofilin-1, non-muscle-specific isoform, in muscle function remains unclear. Mutations LMNA encoding A-type lamins, intermediate filament proteins nuclear envelope, cause autosomal Emery-Dreifuss muscular dystrophy (EDMD). Here, we report increased cofilin-1 expression mutant cells caused by inability proteasome degradation, suggesting a protective ERK1/2. It is known that...
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Abstract The Ciliary Adhesion (CA) complex forms in close association with the basal bodies of cilia during early stages ciliogenesis and is responsible for mediating interactions actin networks multiciliated cells (MCCs). However, its precise localization respect to body accessory structures that lead establishment MCCs are not well understood. Here, we studied distribution CA proteins using super-resolution imaging possible microtubule network. results this study reveal apical at distal...
Nuclear actin is exported from the nucleus via Exportin-6 (XPO6)/RAN GTPase complex. We recently identified that RASSF1A and hippo pathway kinase Mammalian STE20-like protein 2 (MST2) play a pivotal role in nucleocytoplasmic shuttling of by regulating association XPO6 with RAN GTPase. Importantly, loss Ras domain family 1A (RASSF1A) signaling cancer cells highlights key mechanism which nuclear promotes tumorigenesis.
Mitogen-activated protein (MAP) kinases are members of a well-studied family serine/threonine involved in signal transduction pathways, which control multiple cellular processes.The extracellular signal-regulated kinase (ERK1/2) cascade is MAP pathway that transmits signals from the cell surface to substrates either nucleus or cytoplasm.The transmission through ERK1/2 mediated by serial phosphorylations and activations kinases.Abnormal regulation has been linked diseases recent work clearly...
Summary Nuclear actin participates in many essential cellular processes including gene transcription, chromatic remodelling and mRNA processing. Actin shuttles into out the nucleus through action of dedicated transport receptors importin-9 exportin-6, but how this is regulated remains unclear. Here we show that RASSF1A a novel regulator nucleocytoplasmic trafficking required for active maintenance nuclear levels supporting binding exportin-6 (XPO6) to RAN GTPase. (Ras association domain...
Abstract Motile cilia are organelles lining the surfaces of major organs human body and generate directional fluid flow. Ciliary dysfunction has been linked to an emerging class multisystem disorders, collectively known as motile ciliopathies. Drug screening for ciliopathies is challenging due unavailability high-throughput assays that can evaluate ciliary flow generation. Here, we describe development a unique assay enables direct rapid evaluation mucociliary flow, which simultaneously...
<b>Background:</b> Motile cilia dysfunction leads to Primary Ciliary Dyskinesia (PCD), a disease characterised by abnormal mucociliary flow. Drug screening for PCD is challenging due the unavailability of high-throughput assays that can evaluate ciliary flow generation. Here, we describe development unique assay enables direct evaluation as well potential therapeutic agents. <b>Methods:</b> The relies on ability Xenopus tadpoles promote mixing two-phase differential density aqueous mixture,...