2024
Monoclonal antibodies that block Roundabout 1 and 2 signaling target pathological ocular neovascularization through myeloid cells
Geraldo L, Xu Y, Mouthon G, Furtado J, Leser F, Blazer L, Adams J, Zhang S, Zheng L, Song E, Robinson M, Thomas J, Sidhu S, Eichmann A. Monoclonal antibodies that block Roundabout 1 and 2 signaling target pathological ocular neovascularization through myeloid cells. Science Translational Medicine 2024, 16: eadn8388. PMID: 39565875, DOI: 10.1126/scitranslmed.adn8388.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalCorneal NeovascularizationDisease Models, AnimalHumansIntercellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLMyeloid CellsNeovascularization, PathologicNerve Tissue ProteinsReceptors, ImmunologicRetinaRetinal NeovascularizationSignal TransductionConceptsOxygen-induced retinopathyPathological ocular neovascularizationCorneal neovascularizationMyeloid cellsOcular neovascularizationHeterogeneous population of myeloid cellsBlood-retina barrier integrityPopulation of myeloid cellsActivation of myeloid cellsMonoclonal antibodiesOcular neovascular diseasesBlinding eye diseaseHuman monoclonal antibodyExtracellular domainMouse model in vivoModel in vivoMAb treatmentMyeloid populationsOIR retinasNeovascular diseasesVision lossEye diseaseSlit-RoboSlit-Robo signalingBlocking antibodies
2021
SLIT2/ROBO signaling in tumor-associated microglia/macrophages drives glioblastoma immunosuppression and vascular dysmorphia
Geraldo LH, Xu Y, Jacob L, Pibouin-Fragner L, Rao R, Maïssa N, Verreault M, Lemaire N, Knosp C, Lesaffre C, Daubon T, Dejaegher J, Solie L, Rudewicz J, Viel T, Tavitian B, De Vleeschouwer S, Sanson M, Bikfalvi A, Idbaih A, Lu QR, Lima F, Thomas. JL, Eichmann A, Mathivet T. SLIT2/ROBO signaling in tumor-associated microglia/macrophages drives glioblastoma immunosuppression and vascular dysmorphia. Journal Of Clinical Investigation 2021, 131 PMID: 34181595, PMCID: PMC8363292, DOI: 10.1172/jci141083.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsDisease ProgressionGene Expression Regulation, NeoplasticGene Knockdown TechniquesGlioblastomaHeterograftsHumansImmune ToleranceIntercellular Signaling Peptides and ProteinsMacrophagesMiceMice, Inbred C57BLMicrogliaNerve Tissue ProteinsPrognosisReceptors, ImmunologicSignal TransductionTumor MicroenvironmentConceptsSLIT2/ROBOTumor growthPatient-derived GBM xenograftsTumor microenvironmentKnockdown of SLIT2Tumor vessel functionMouse glioma cellsImmunotherapeutic targetPoor survivalGBM xenograftsBrain tumorsGBM microenvironmentMacrophage invasionSLIT2 expressionMalignant progressionVessel functionMacrophage chemotaxisGlioma cellsEnhanced efficacySLIT2Migration of cellsImmunosuppressionImmunotherapyGene expression profilesRoundabout 1
2019
Endophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis
Genet G, Boyé K, Mathivet T, Ola R, Zhang F, Dubrac A, Li J, Genet N, Henrique Geraldo L, Benedetti L, Künzel S, Pibouin-Fragner L, Thomas JL, Eichmann A. Endophilin-A2 dependent VEGFR2 endocytosis promotes sprouting angiogenesis. Nature Communications 2019, 10: 2350. PMID: 31138815, PMCID: PMC6538628, DOI: 10.1038/s41467-019-10359-x.Peer-Reviewed Original ResearchMeSH KeywordsAcyltransferasesAnimalsCell MovementCell PolarityCell ProliferationCell SurvivalEndocytosisEndothelial CellsIntercellular Signaling Peptides and ProteinsMAP Kinase Signaling SystemMiceMice, KnockoutNeovascularization, PhysiologicNerve Tissue ProteinsP21-Activated KinasesReceptors, ImmunologicRetinal VesselsVascular Endothelial Growth Factor Receptor-2ConceptsEndophilin A2Endothelial cell migrationSprouting angiogenesisCell migrationFront-rear polarityBAR domain proteinsFront-rear polarizationClathrin-independent internalizationSpecific endocytic pathwaysVEGFR2 endocytosisEndocytic pathwayAngiogenesis defectsEffector PAKTip cellsSlit-RoboActivation of VEGFR2Downstream activationVEGFR2 internalizationCell behaviorPathological angiogenesisCritical mediatorEndocytosisPathological conditions