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 antibodiesVEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model
Boisserand L, Geraldo L, Bouchart J, Kamouh M, Lee S, Sanganahalli B, Spajer M, Zhang S, Lee S, Parent M, Xue Y, Skarica M, Yin X, Guegan J, Boyé K, Leser F, Jacob L, Poulet M, Li M, Liu X, Velazquez S, Singhabahu R, Robinson M, Askenase M, Osherov A, Sestan N, Zhou J, Alitalo K, Song E, Eichmann A, Sansing L, Benveniste H, Hyder F, Thomas J. VEGF-C prophylaxis favors lymphatic drainage and modulates neuroinflammation in a stroke model. Journal Of Experimental Medicine 2024, 221: e20221983. PMID: 38442272, PMCID: PMC10913814, DOI: 10.1084/jem.20221983.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factor-CDeep cervical lymph nodesCentral nervous systemEffect of vascular endothelial growth factor-CMeningeal lymphatic vesselsAmeliorated motor performanceCervical lymph nodesIschemic strokeVEGF-C overexpressionIncreased BDNF signalingAcute ischemic strokeBrain cellsIncreased CSF drainageIschemic stroke outcomesModel of ischemic strokeMouse model of ischemic strokeImmune surveillanceCSF drainageLymph nodesFluid drainageNucleus RNA sequencingLymphatic growthLymphatic drainageMouse modelBDNF signalingComplementary and Inducible creERT2 Mouse Models for Functional Evaluation of Endothelial Cell Subtypes in the Bone Marrow
Poulos M, Ramalingam P, Winiarski A, Gutkin M, Katsnelson L, Carter C, Pibouin-Fragner L, Eichmann A, Thomas J, Miquerol L, Butler J. Complementary and Inducible creERT2 Mouse Models for Functional Evaluation of Endothelial Cell Subtypes in the Bone Marrow. Stem Cell Reviews And Reports 2024, 20: 1135-1149. PMID: 38438768, PMCID: PMC11087254, DOI: 10.1007/s12015-024-10703-9.Peer-Reviewed Original ResearchBone marrowEndothelial cellsMouse modelAdult bone marrowArteriole endothelial cellsAdult BMOff-target activityHematopoietic dysfunctionAdult marrowHematopoietic homeostasisEndothelial cell subtypesVascular subtypeCre-expressing lineEndothelial subtypesEndothelial-specificMouse linesHSC activationCell subtypesEC subtypesParacrine signalingPerivascular cellsModulate HSC activationMarrowSubtypesAdult endotheliumCompartmentalized ocular lymphatic system mediates eye–brain immunity
Yin X, Zhang S, Lee J, Dong H, Mourgkos G, Terwilliger G, Kraus A, Geraldo L, Poulet M, Fischer S, Zhou T, Mohammed F, Zhou J, Wang Y, Malloy S, Rohner N, Sharma L, Salinas I, Eichmann A, Thomas J, Saltzman W, Huttner A, Zeiss C, Ring A, Iwasaki A, Song E. Compartmentalized ocular lymphatic system mediates eye–brain immunity. Nature 2024, 628: 204-211. PMID: 38418880, PMCID: PMC10990932, DOI: 10.1038/s41586-024-07130-8.Peer-Reviewed Original ResearchResponse to herpes simplex virusCentral nervous systemImmune response to herpes simplex virusPosterior eyeImmune responseTherapeutic immune responsesOptic nerve sheathCervical lymph nodesAdeno-associated virusCNS diseaseDeep cervical lymph nodesHerpes simplex virusImmune protected miceCentral nervous system tissueLymphatic drainage systemImmunological featuresAnatomical extensionNerve sheathOptic nerveGene therapyLymph nodesMultiple dosesSimplex virusLymphatic circuitLymphatic signal
2023
Editorial Expression of Concern: The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system
Lu X, le Noble F, Yuan L, Jiang Q, de Lafarge B, Sugiyama D, Bréant C, Claes F, De Smet F, Thomas J, Autiero M, Carmeliet P, Tessier-Lavigne M, Eichmann A. Editorial Expression of Concern: The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 2023, 625: e12-e12. PMID: 38110575, DOI: 10.1038/s41586-023-06944-2.Peer-Reviewed Original ResearchCCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma
Geraldo L, Garcia C, Xu Y, Leser F, Grimaldi I, de Camargo Magalhães E, Dejaegher J, Solie L, Pereira C, Correia A, De Vleeschouwer S, Tavitian B, Canedo N, Mathivet T, Thomas J, Eichmann A, Lima F. CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma. Cellular And Molecular Life Sciences 2023, 80: 179. PMID: 37314567, PMCID: PMC10267017, DOI: 10.1007/s00018-023-04788-7.Peer-Reviewed Original ResearchConceptsMicroglia/macrophage recruitmentC chemokine receptor type 7CCL21-CCR7Central nervous systemMacrophage recruitmentTumor microenvironmentChemokine receptor type 7Fatal primary tumorMouse GBM modelsChemokine ligand 21Potential therapeutic targetVEGF-A productionTumor cell deathCCR7 expressionTherapeutic optionsPrimary tumorPoor survivalCurrent treatmentGBM patientsTumor cell migrationTherapeutic targetBrain cancerNervous systemChemotherapy resistanceLigand 21Connexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone
Genet N, Genet G, Chavkin N, Paila U, Fang J, Vasavada H, Goldberg J, Acharya B, Bhatt N, Baker K, McDonnell S, Huba M, Sankaranarayanan D, Ma G, Eichmann A, Thomas J, Ffrench-Constant C, Hirschi K. Connexin 43-mediated neurovascular interactions regulate neurogenesis in the adult brain subventricular zone. Cell Reports 2023, 42: 112371. PMID: 37043357, PMCID: PMC10564973, DOI: 10.1016/j.celrep.2023.112371.Peer-Reviewed Original ResearchConceptsSubventricular zoneEndothelial cellsNSC proliferationNSC quiescenceAdult brain subventricular zoneBlood-brain barrierBrain subventricular zoneStem cell therapyNeural stem cell nicheNeurovascular interactionsNeuroblast generationAdult brainSingle-cell RNA sequencingNeurodegenerative disordersChannel-independent mannerCell therapySVZ-NSCsConnexin 43Expression of genesERK activationNSC regulationNSC behaviorRNA sequencingCx43Proliferation
2011
Vascular endothelial growth factor receptor 3 directly regulates murine neurogenesis
Calvo CF, Fontaine RH, Soueid J, Tammela T, Makinen T, Alfaro-Cervello C, Bonnaud F, Miguez A, Benhaim L, Xu Y, Barallobre MJ, Moutkine I, Lyytikkä J, Tatlisumak T, Pytowski B, Zalc B, Richardson W, Kessaris N, Garcia-Verdugo JM, Alitalo K, Eichmann A, Thomas JL. Vascular endothelial growth factor receptor 3 directly regulates murine neurogenesis. Genes & Development 2011, 25: 831-844. PMID: 21498572, PMCID: PMC3078708, DOI: 10.1101/gad.615311.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedEnzyme-Linked Immunosorbent AssayImmunohistochemistryLymphangiogenesisMiceMice, Mutant StrainsMicroscopy, Electron, TransmissionNeovascularization, PhysiologicNeural Stem CellsNeurogenesisOligonucleotide Array Sequence AnalysisReverse Transcriptase Polymerase Chain ReactionVascular Endothelial Growth Factor Receptor-3ConceptsNeural stem cellsSubventricular zoneVEGF receptorsNeural cellsVEGFR-3Vascular endothelial growth factor (VEGF) familyEndothelial growth factor familyVascular endothelial growth factor receptor 3VEGFR-3 expressionMultipotent neural stem cellsCapillary endothelial cellsGrowth factor receptor 3Overexpression of VEGFGrowth factor familyAdult neurogenesisSVZ neurogenesisReporter miceReceptor 3NeurogenesisNeurodegenerative diseasesConditional deletionEndothelial cellsGrowth factorLigand VEGFInducible deletionRobo4 Maintains Vessel Integrity and Inhibits Angiogenesis by Interacting with UNC5B
Koch AW, Mathivet T, Larrivée B, Tong RK, Kowalski J, Pibouin-Fragner L, Bouvrée K, Stawicki S, Nicholes K, Rathore N, Scales SJ, Luis E, del Toro R, Freitas C, Bréant C, Michaud A, Corvol P, Thomas JL, Wu Y, Peale F, Watts RJ, Tessier-Lavigne M, Bagri A, Eichmann A. Robo4 Maintains Vessel Integrity and Inhibits Angiogenesis by Interacting with UNC5B. Developmental Cell 2011, 20: 33-46. PMID: 21238923, DOI: 10.1016/j.devcel.2010.12.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BlockingBlood VesselsCapillary PermeabilityEnzyme ActivationHumansLigandsMiceModels, BiologicalNeovascularization, PathologicNerve Tissue ProteinsNetrin ReceptorsProtein BindingReceptors, Cell SurfaceReceptors, ImmunologicRetinal VesselsSignal Transductionsrc-Family KinasesSus scrofaVascular Endothelial Growth Factor AConceptsProtein-protein interaction screenVascular endothelial growth factorFunction-blocking monoclonal antibodiesInteraction screenNovel functionGuidance receptorsExtracellular domainNetrin receptorsReceptor familyVessel integrityReceptor interactionInhibits angiogenesisRobo4Unexpected interactionsGrowth factorEndothelial cellsUNC5BVascular integrityEndothelial growth factorAngiogenesisIncreases angiogenesisReceptorsMonoclonal antibodiesIntegrityProtein
2010
Neuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3
Xu Y, Yuan L, Mak J, Pardanaud L, Caunt M, Kasman I, Larrivée B, del Toro R, Suchting S, Medvinsky A, Silva J, Yang J, Thomas J, Koch A, Alitalo K, Eichmann A, Bagri A. Neuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3. Journal Of Experimental Medicine 2010, 207: i1-i1. DOI: 10.1084/jem2071oia1.Peer-Reviewed Original Research
2004
The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system
Lu X, le Noble F, Yuan L, Jiang Q, de Lafarge B, Sugiyama D, Bréant C, Claes F, De Smet F, Thomas JL, Autiero M, Carmeliet P, Tessier-Lavigne M, Eichmann A. The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 2004, 432: 179-186. PMID: 15510105, DOI: 10.1038/nature03080.Peer-Reviewed Original ResearchConceptsNetrin receptor UNC5BEndothelial tip cell filopodiaTip cell filopodiaReceptor UNC5BEndothelial tip cellsVascular systemNetrin-1aTip cellsEndothelial cellsProper wiringAxon guidanceCell filopodiaNetrin receptorsGuidance eventsFilopodial retractionMorphogenesisUNC5BVessel branchingAberrant extensionAnatomical similaritiesNetrin-1CellsZebrafishGenesGuidance function