Alexandre Dubrac

ORCID: 0000-0002-3829-2577
Publications
Citations
Views
---
Saved
---
About
Contact & Profiles
Research Areas
  • Chemokine receptors and signaling
  • Angiogenesis and VEGF in Cancer
  • Cancer Mechanisms and Therapy
  • Retinal Diseases and Treatments
  • Axon Guidance and Neuronal Signaling
  • Retinal Imaging and Analysis
  • Vascular Malformations and Hemangiomas
  • Retinal Development and Disorders
  • Cell Adhesion Molecules Research
  • Vascular Anomalies and Treatments
  • Vascular Malformations Diagnosis and Treatment
  • Immunotherapy and Immune Responses
  • Lymphatic System and Diseases
  • Hippo pathway signaling and YAP/TAZ
  • RNA Research and Splicing
  • Endoplasmic Reticulum Stress and Disease
  • Phagocytosis and Immune Regulation
  • Moyamoya disease diagnosis and treatment
  • Platelet Disorders and Treatments
  • Barrier Structure and Function Studies
  • Multiple Myeloma Research and Treatments
  • Fibroblast Growth Factor Research
  • Monoclonal and Polyclonal Antibodies Research
  • Zebrafish Biomedical Research Applications
  • Glycosylation and Glycoproteins Research

Yale University
2013-2024

Centre Hospitalier Universitaire Sainte-Justine
2020-2024

Université de Montréal
2020-2024

Inserm
2010-2016

Université de Bordeaux
2010-2016

Centre de Recherche en Cancérologie de Toulouse
2012-2016

Université Toulouse III - Paul Sabatier
2010-2016

Centre Interdisciplinaire de Recherche en Biologie
2015-2016

Collège de France
2015-2016

Paris Cardiovascular Research Center
2016

Zipping up obesity Chylomicrons are specialized particles that carry dietary fats from the intestine to bloodstream for absorption into body. Lacteals lymphatic vessels act as highway chylomicron transport, but it is unclear how passage occurs. Zhang et al. report two endothelial cell receptors, neuropilin-1 (NRP1) and vascular growth factor receptor 1 (VEGFR1, also known FLT1), required convert entry spaces between lacteals open junctions closed, zipped structures (see Perspective by...

10.1126/science.aap9331 article EN Science 2018-08-10

Morphogenesis of the vascular system is strongly modulated by mechanical forces from blood flow. Hereditary hemorrhagic telangiectasia (HHT) an inherited autosomal-dominant disease in which arteriovenous malformations and telangiectasias accumulate with age. Most cases are linked to heterozygous mutations Alk1 or Endoglin, receptors for bone morphogenetic proteins (BMPs) 9 10. Evidence suggests that a second hit results clonal expansion endothelial cells form lesions poor mural cell coverage...

10.1083/jcb.201603106 article EN cc-by-nc-sa The Journal of Cell Biology 2016-09-19

Sprouting angiogenesis drives blood vessel growth in healthy and diseased tissues. Vegf Dll4/Notch signalling cooperate a negative feedback loop that specifies endothelial tip stalk cells to ensure adequate branching function. Current concepts posit default the tip-cell phenotype when Notch is inactive. Here we identify instead stalk-cell needs be actively repressed allow formation. We show this key function of neuropilin-1 (Nrp1), which suppresses by limiting Smad2/3 activation through Alk1...

10.1038/ncomms8264 article EN cc-by Nature Communications 2015-06-17

Activin receptor-like kinase 1 (ALK1) is an endothelial serine-threonine receptor for bone morphogenetic proteins (BMPs) 9 and 10. Inactivating mutations in the ALK1 gene cause hereditary haemorrhagic telangiectasia type 2 (HHT2), a disabling disease characterized by excessive angiogenesis with arteriovenous malformations (AVMs). Here we show that inducible, endothelial-specific homozygous Alk1 inactivation BMP9/10 ligand blockade both lead to AVM formation postnatal retinal vessels internal...

10.1038/ncomms13650 article EN cc-by Nature Communications 2016-11-29

Background: Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular disorder that causes arteriovenous malformations (AVMs). Mutations in the genes encoding Endoglin ( ENG ) and activin-receptor-like kinase 1 AVCRL1 ALK1) cause HHT type 2, respectively. SMAD4 gene are present families with juvenile polyposis-HHT syndrome involves AVMs. a downstream effector of transforming growth factor-β (TGFβ)/bone morphogenetic protein (BMP) family ligands signal via activin-like receptors...

10.1161/circulationaha.118.033842 article EN Circulation 2018-07-05

Regulation of vascular endothelial growth factor receptor-2 (VEGFR2) signaling is a control point that determines the extent tree formation. Recent studies demonstrated an important role played by VEGFR2 trafficking in its activity and suggested involvement phosphotyrosine phosphatase 1b (PTP1b) this process. This study was designed to define PTP1b regulation angiogenesis arteriogenesis.We generated mice carrying endothelial-specific deletion examined effect knockout on VEGF signaling,...

10.1161/circulationaha.114.009683 article EN Circulation 2014-07-01

Abstract Endothelial cell migration, proliferation and survival are triggered by VEGF-A activation of VEGFR2. However, how these behaviors regulated individually is still unknown. Here we identify Endophilin-A2 (ENDOA2), a BAR-domain protein that orchestrates CLATHRIN-independent internalization, as critical mediator endothelial migration sprouting angiogenesis. We show EndoA2 knockout mice exhibit postnatal angiogenesis defects impaired front-rear polarization tip cells. ENDOA2 deficiency...

10.1038/s41467-019-10359-x article EN cc-by Nature Communications 2019-05-28

Endothelial tip cells guiding tissue vascularization are primary targets for angiogenic therapies. Whether require differential signals to develop their complex branching patterns remained unknown. Here, we show that diving invading the mouse neuroretina (D-tip cells) distinct from superficial retinal vascular plexus (S-tip cells). D-tip have a unique transcriptional signature, including high TGF-β signaling, and they begin acquire blood-retina barrier properties. deletion of receptor I...

10.1016/j.devcel.2021.06.021 article EN cc-by-nc-nd Developmental Cell 2021-07-16

Sprouting angiogenesis is a key process driving blood vessel growth in ischemic tissues and an important drug target number of diseases, including wet macular degeneration wound healing. Endothelial cells forming the sprout must develop front-rear polarity to allow extension. The adaptor proteins Nck1 2 are known regulators cytoskeletal dynamics polarity, but their function poorly understood. Here, we show that Nck adaptors required for endothelial cell migration downstream angiogenic...

10.1161/circulationaha.115.017537 article EN Circulation 2015-12-10

Abstract Pericytes are mural cells that surround capillaries and control angiogenesis capillary barrier function. During sprouting angiogenesis, endothelial cell-derived platelet-derived growth factor-B (PDGF-B) regulates pericyte proliferation migration via the factor receptor-β (PDGFRβ). PDGF-B overexpression has been associated with proliferative retinopathy, but underlying mechanisms remain poorly understood. Here we show abnormal, α-SMA-expressing pericytes cover angiogenic sprouts...

10.1038/s41467-018-05926-7 article EN cc-by Nature Communications 2018-08-21

Aberrant blood vessel formation contributes to a wide variety of pathologies, and factors that regulate angiogenesis are attractive therapeutic targets. Endothelial smooth muscle cell-derived neuropilin-like protein (ESDN) is neuropilin-related transmembrane expressed in ECs; however, its potential effect on VEGF responses remains undefined. Here, we generated global EC-specific Esdn knockout mice demonstrated ESDN promotes VEGF-induced human murine EC proliferation migration. Deletion the...

10.1172/jci67752 article EN Journal of Clinical Investigation 2013-10-31

The activation of translation contributes to malignant transformation and is an emerging target for cancer therapies. RNA G-quadruplex structures are general inhibitors cap-dependent mRNA were recently shown be targeted oncoprotein translational activation. In contrast however, the within 5'UTR human vascular endothelial growth factor A (VEGF) has been essential IRES-mediated translation. Since VEGF a pivotal role in tumor angiogenesis major anti-tumoral therapies, we investigated...

10.1080/15476286.2015.1017236 article EN RNA Biology 2015-03-04

Abstract Vascular permeability and neovascularization are implicated in many diseases including retinopathies diabetic wound healing. Robo4 is an endothelial-specific transmembrane receptor that stabilizes the vasculature, as shown −/− mice develop hyperpermeability, but how signals remained unclear. Here we show deletion enhances revascularization oxygen-induced retinopathy (OIR) accelerates cutaneous To determine signalling pathways, generated transgenic expressing a truncated lacking...

10.1038/ncomms13517 article EN cc-by Nature Communications 2016-11-24

BACKGROUND: Heterogeneity in the severity of cerebral cavernous malformations (CCMs) disease, including brain bleedings and thrombosis that cause neurological disabilities patients, suggests environmental, genetic, or biological factors act as disease modifiers. Still, underlying mechanisms are not entirely understood. Here, we report mild hypoxia accelerates CCM by promoting angiogenesis, neuroinflammation, vascular brains mouse models. METHODS: We used genetic studies, RNA sequencing,...

10.1161/atvbaha.123.320367 article EN Arteriosclerosis Thrombosis and Vascular Biology 2024-04-25

Abstract Zonula occludens-1 (ZO-1) is involved in the regulation of cell-cell junctions between endothelial cells (ECs). Here we identify ZO-1 protein interactome and uncover interactions with RNA-binding proteins that are part stress granules (SGs). Downregulation increased SG formation response to protected ECs from cellular insults. The uncovered an association Y-box binding 1 (YB-1), a constituent SGs. Arsenite treatment decreased interaction YB-1, drove assembly. YB-1 expression...

10.1038/s41467-024-48852-7 article EN cc-by Nature Communications 2024-05-23

// Arnaud Jabouille 1, 2 , Maylis Delugin Raphaël Pineau Alexandre Dubrac 3 Fabienne Soulet Stéphanie Lhomond 2, 4 Nestor Pallares-Lupon Hervé Prats Andreas Bikfalvi Eric Chevet 4, 5, 6 Christian Touriol Michel Moenner 7 1 Inserm, U1029, 33400 Talence, France Univ. Bordeaux, 33000 U1037, CHU de Rangueil, 31432 Toulouse, U1053, 5 Centre Régional Lutte Contre le Cancer Eugène Marquis, 35000 Rennes, ER440, « Oncogenesis, stress, signaling » Rennes...

10.18632/oncotarget.4679 article EN Oncotarget 2015-07-23

Glycosphingolipids, which are abundant at the surface of melanoma cells, play crucial roles in tumor progression. We investigated whether a newly described glycosphingolipid hydrolase, encoded by GBA2 gene, can modulate human cell growth and death. expression was quantified on cells RT-qPCR. The antiproliferative effects were assessed expressing inducible established xenografts. As control an catalytically inactive mutant generated. Sphingolipid levels monitored mass spectrometry; unfolded...

10.1096/fj.12-215152 article EN The FASEB Journal 2012-10-16

The CXCL4 paralog CXCL4L1 is a less studied chemokine that has been suggested to exert an antiangiogenic function. However, also expressed in patient tumors, tumor cell lines, and murine xenografts, prompting more detailed analysis of its role cancer pathogenesis. We used genetic antibody-based approaches attenuate models pancreatic ductal adenocarcinoma (PDAC). Mechanisms expression were assessed coculture experiments, murine, avian xenotransplants, including through evaluation CpG...

10.1158/0008-5472.can-15-2864 article EN Cancer Research 2016-09-10

Cardiac tissue cohesion relying on highly ordered cardiomyocytes (CM) interactions is critical because most cardiomyopathies are associated with remodeling and architecture alterations.Eph/ephrin system constitutes a ubiquitous coordinating cellular communications which recently emerged as major regulator in adult organs. We examined if eph/ephrin could participate cardiac cyto-organization.We reported the expression of ephrin-B1 both endothelial cells for first time CMs where localized...

10.1161/circresaha.111.262451 article EN Circulation Research 2012-02-04
Coming Soon ...