A5045238444- Wnt/β-catenin signaling in development and cancer
- Kruppel-like factors research
- Liver physiology and pathology
- Hippo pathway signaling and YAP/TAZ
- Zebrafish Biomedical Research Applications
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Platelet Disorders and Treatments
- Protein Tyrosine Phosphatases
- Angiogenesis and VEGF in Cancer
- Ubiquitin and proteasome pathways
- Congenital heart defects research
- Moyamoya disease diagnosis and treatment
- Retinal Diseases and Treatments
- Acute Myeloid Leukemia Research
- Retinopathy of Prematurity Studies
- COVID-19 Clinical Research Studies
- Blood Coagulation and Thrombosis Mechanisms
- Long-Term Effects of COVID-19
- Lymphatic System and Diseases
- Connective tissue disorders research
- Hormonal Regulation and Hypertension
- Neuroinflammation and Neurodegeneration Mechanisms
- Birth, Development, and Health
- Cerebrovascular and genetic disorders
- Developmental Biology and Gene Regulation
Université de Bordeaux
2014-2024
Inserm
2014-2024
Biologie des maladies cardiovasculaires
2018-2024
Imperial College London
2016-2022
Lung Institute
2019-2021
National Institute for Health Research
2021
NIHR Imperial Biomedical Research Centre
2020
Centre Hospitalier Universitaire de Bordeaux
2016
Hammersmith Hospital
2016
Hôpital Cardiologique du Haut-Lévêque
2015
Thrombosis is the main cause of morbidity and mortality in patients with JAK2V617F myeloproliferative neoplasms. Recent studies have reported presence endothelial cells some We investigated role that express thrombus formation using an vitro model human overexpressing vivo mice endothelial-specific expression. Interestingly, these displayed a higher propensity for thrombus. When deciphering mechanisms by which JAK2V617F-expressing promote thrombosis, we observed they pro-adhesive phenotype...
Rationale: The ETS (E-26 transformation-specific) transcription factor ERG (ETS-related gene) is essential for endothelial homeostasis, driving expression of lineage genes and repressing proinflammatory genes. Loss associated with diseases including atherosclerosis. ERG’s homeostatic function lineage-specific, because aberrant in cancer oncogenic. molecular basis lineage-specific activity unknown. Transcriptional regulation specificity linked to enhancer clusters (super-enhancers)....
The role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how endothelial transcription factor ETS-related gene (ERG) promotes homoeostasis by controlling canonical TGFβ-SMAD signalling, driving SMAD1 pathway while repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3, restricting its access DNA. Ablation expression results endothelial-to-mesenchymal transition (EndMT) spontaneous fibrogenesis...
Abstract Notch and Angiopoietin-1 (Ang1)/Tie2 pathways are crucial for vascular maturation stability. Here we identify the transcription factor ERG as a key regulator of endothelial signalling. We show that controls balance between ligands by driving Delta-like ligand 4 (Dll4) while repressing Jagged1 (Jag1) expression. In vivo , this regulation occurs selectively in maturing plexus mouse developing retina, where Ang1/Tie2 signalling is active. find mediates Ang1-dependent required...
Angiogenesis involves the coordinated growth and migration of endothelial cells (ECs) toward a proangiogenic signal. The Wnt planar cell polarity (PCP) pathway, through recruitment Dishevelled (Dvl) Dvl-associated activator morphogenesis (Daam1), has been proposed to regulate actin cytoskeleton microtubule (MT) reorganization for oriented migration. Here we report that Kif26b--a kinesin--and Daam1 cooperatively initiation EC sprouting directional via MT reorganization. First, find Kif26b is...
Vascular permeability is essential for the health of normal tissues and an important characteristic many disease states. The role Wnt/frizzled pathway in vascular biology has recently been reported. objectives this study are to analyse Frizzled7 (Fzd7) receptor control integrity. Fzd7 expressed endothelial cells accumulates at points cell–cell contact association with VE-cadherin β-catenin, two major adherens junction molecules. To selectively delete fzd7 vasculature, we developed gene...
Abstract Endothelial cells actively maintain an anti-thrombotic environment; loss of this protective function may lead to thrombosis and systemic coagulopathy. The transcription factor ERG is essential endothelial homeostasis. Here, we show that inducible deletion ( Erg iEC-KO ) in mice associated with spontaneous thrombosis, hemorrhages We find drives the anticoagulant thrombomodulin (TM), as shown by reporter assays chromatin immunoprecipitation. TM expression regulated shear stress (SS)...
Objective— Vessel formation requires precise orchestration of a series morphometric and molecular events controlled by multitude angiogenic factors morphogens. Wnt/frizzled signaling is required for proper vascular formation. In this study, we investigated the role Fzd7 (frizzled-7) receptor in retinal development its relationship with Wnt/β-catenin canonical pathway Notch signaling. Approach Results— Using transgenic mice, demonstrated that postnatal Endothelial cell (EC) deletion fzd7 (...
Transcription factor networks are crucial for the regulation of endothelial cell gene expression during vascular development and homeostasis. A recent analysis 269 rare diseases in 77,539 individuals revealed an association between loss-of-function variants ERG, encoding ETS transcription factor, with primary lymphoedema. However, pathogenicity such possible mechanisms ERG-associated lymphatic vessel dysfunction remains to be established. Here, we have further identified characterised...
Background Hypertension is a leading cause of microvascular injury, yet the genetic determinants organ-specific vulnerability remain poorly understood. Yest, we need good mouse models to investigate complication hypertension. This study investigates role background in shaping hypertensive complications by comparing two strains with divergent inflammatory responses. Methods Three-month-old 129S1/SvlmJ and C57BL/6J mice received 600 ng/kg/min angiotensin II (AngII) or saline. We compared...
<title>Abstract</title> Cerebral small vessel disease (cSVD) is a leading cause of stroke, cognitive decline and dementia, for which no specific mechanism-based treatments are currently available. Previous genomic studies identified associations common variants at chr17q25 with cSVD features, converging evidence causal involvement TRIM47, an ubiquitin ligase enriched in brain endothelial cells (ECs). In the present study, we devised multilayered experimental plan to decipher biological...
Abstract Retinopathies remain major causes of visual impairment in diabetic patients and premature infants. Introduction anti‐angiogenic drugs targeting vascular endothelial growth factor (VEGF) has transformed therapy for these proliferative retinopathies. However, limitations associated with anti‐VEGF medications require to unravel new pathways vessel identify potential drug targets. Here, we investigated the role Wnt/Frizzled‐7 (Fzd7) pathway a mouse model oxygen‐induced retinopathy...
Abstract Cerebral small vessel disease (cSVD) is a leading cause of stroke, cognitive decline and dementia, for which no specific mechanism-based treatments are available to date. Genome-wide whole-exome association studies previously identified robust associations common variants at chr17q25 with cSVD features on magnetic resonance imaging, converging bioinformatic experimental data causal involvement TRIM47 . Preliminary functional evaluation TRIM47, an ubiquitin ligase enriched in brain...
Abstract A striking feature of severe COVID-19 is thrombosis in large as well small vessels multiple organs. This has led to the assumption that SARS-CoV-2 virus directly infects and damages vascular endothelium. However, endothelial expression ACE2, cellular receptor for SARS-CoV-2, not been convincingly demonstrated. Interrogating human bulk single-cell transcriptomic data, we found ACE2 cells be extremely low or absent vivo upregulated by exposure inflammatory agents vitro . Also,...