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 antibodiesMeningeal lymphatic vessel dysfunction driven by CGRP signaling causes migraine-like pain in mice
Thomas J, Schindler E, Gottschalk C. Meningeal lymphatic vessel dysfunction driven by CGRP signaling causes migraine-like pain in mice. Journal Of Clinical Investigation 2024, 134: e182556. PMID: 39087472, PMCID: PMC11290958, DOI: 10.1172/jci182556.Peer-Reviewed Original ResearchConceptsBlocking CGRP signalingCGRP receptor componentsMigraine-like painCervical lymph nodesGap junction proteinPrimary headache disordersLymphatic vessel dysfunctionAcute migrainePharmacological blockadeLymph nodesHeadache disordersNeurological symptomsJunction proteinsCGRPLymphatic vesselsMeningeal lymphatic vesselsInducible knockoutVessel dysfunctionMigraineReceptor componentsHeadachePainPathophysiologyDysfunctionMice
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
2017
Development and plasticity of meningeal lymphatic vessels
Antila S, Karaman S, Nurmi H, Airavaara M, Voutilainen MH, Mathivet T, Chilov D, Li Z, Koppinen T, Park JH, Fang S, Aspelund A, Saarma M, Eichmann A, Thomas JL, Alitalo K. Development and plasticity of meningeal lymphatic vessels. Journal Of Experimental Medicine 2017, 214: 3645-3667. PMID: 29141865, PMCID: PMC5716035, DOI: 10.1084/jem.20170391.Peer-Reviewed Original ResearchAnimalsAnimals, NewbornBiological TransportCerebrospinal FluidDependovirusGene DeletionHumansIndolesInjections, IntraventricularLymph NodesLymphangiogenesisLymphatic VesselsMaleMeningesMice, Inbred C57BLMicrospheresMyocytes, Smooth MuscleProtein Kinase InhibitorsPyrrolesSignal TransductionSpinal CordSunitinibVascular Endothelial Growth Factor CVascular Endothelial Growth Factor DVascular Endothelial Growth Factor Receptor-3
2015
Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans
Han J, Calvo CF, Kang TH, Baker KL, Park JH, Parras C, Levittas M, Birba U, Pibouin-Fragner L, Fragner P, Bilguvar K, Duman RS, Nurmi H, Alitalo K, Eichmann AC, Thomas JL. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans. Cell Reports 2015, 10: 1158-1172. PMID: 25704818, PMCID: PMC4685253, DOI: 10.1016/j.celrep.2015.01.049.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationCells, CulturedEmbryonic Stem CellsExtracellular Signal-Regulated MAP KinasesHippocampusHumansMiceMice, Inbred C57BLNeural Stem CellsNeurogenesisProto-Oncogene Proteins c-aktRecombinant ProteinsSignal TransductionVascular Endothelial Growth Factor CVascular Endothelial Growth Factor Receptor-3ConceptsHuman embryonic stem cellsNeural stem cellsVascular endothelial growth factor receptor 3Growth factor receptor 3NSC activationStem cellsProgenitor cellsAdult hippocampal neural stem cellsEmbryonic stem cellsNeural stem cell activationStem cell activationQuiescent neural stem cellsNeural progenitor cellsCell fateReceptor 3Specific regulatorsAdult mammalian hippocampusMolecular mechanismsCell cycleHippocampal neural stem cellsLigand VEGFERK pathwayConditional deletionNew neuronsVEGFR3
2014
Neural-Specific Deletion of Htra2 Causes Cerebellar Neurodegeneration and Defective Processing of Mitochondrial OPA1
Patterson VL, Zullo AJ, Koenig C, Stoessel S, Jo H, Liu X, Han J, Choi M, DeWan AT, Thomas JL, Kuan CY, Hoh J. Neural-Specific Deletion of Htra2 Causes Cerebellar Neurodegeneration and Defective Processing of Mitochondrial OPA1. PLOS ONE 2014, 9: e115789. PMID: 25531304, PMCID: PMC4274161, DOI: 10.1371/journal.pone.0115789.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBehavior, AnimalBlotting, WesternCell ProliferationCerebellumFemaleGTP PhosphohydrolasesHigh-Temperature Requirement A Serine Peptidase 2MaleMiceMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial ProteinsNerve DegenerationNeuronsParkinson DiseaseReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSequence DeletionSerine EndopeptidasesSignal TransductionConceptsNeural-specific deletionStriatal neuronal lossPostnatal day 18Days of ageNeuronal lossNeurological symptomsParkinson's diseaseMouse modelParkinsonian phenotypeSystemic effectsMitochondrial Opa1Day 18Premature deathMutant miceNeural contributionsMiceCerebellar neurodegenerationKey moleculesStructural anomaliesAbnormal activityAbnormal morphologyCerebellumDiseaseComplete penetranceDeath
2013
Interactions between VEGFR and Notch signaling pathways in endothelial and neural cells
Thomas JL, Baker K, Han J, Calvo C, Nurmi H, Eichmann AC, Alitalo K. Interactions between VEGFR and Notch signaling pathways in endothelial and neural cells. Cellular And Molecular Life Sciences 2013, 70: 1779-1792. PMID: 23479133, PMCID: PMC3648205, DOI: 10.1007/s00018-013-1312-6.Peer-Reviewed Original ResearchConceptsCell fate decisionsDifferent cell contextsTyrosine kinase VEGF receptorsExtracellular matrix moleculesCell interaction mechanismsMetazoan speciesFate decisionsGrowth factorCanonical NotchVascular endothelial growth factorNotch receptorsCell contextEnvironmental cuesDynamic regulationMolecular relationshipsKey regulatorNotch pathwayMatrix moleculesNeural cellsCell contactAdjacent cellsPathwayVEGF receptorsCellsNeurovascular interactions
2012
Molecular Parallels between Neural and Vascular Development
Eichmann A, Thomas JL. Molecular Parallels between Neural and Vascular Development. Cold Spring Harbor Perspectives In Medicine 2012, 3: a006551. PMID: 23024177, PMCID: PMC3530036, DOI: 10.1101/cshperspect.a006551.Peer-Reviewed Original ResearchConceptsCentral nervous systemAdult neurogenic nichesMolecular parallelsNeural stem cellsCardiac outputMolecular mechanismsBlood vesselsNeurovascular interactionsVascular developmentHuman diseasesStem cellsCNS blood vesselsHuman central nervous systemBlood-brain barrierVascular endothelial growth factorNeurogenic nicheCell populationsEndothelial growth factorGrowth factorEndothelial cellsBlood glucoseNervous systemImportant roleCellsUnique population
2011
Robo4 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
2007
Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis?
Williams A, Piaton G, Aigrot MS, Belhadi A, Théaudin M, Petermann F, Thomas JL, Zalc B, Lubetzki C. Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis? Brain 2007, 130: 2554-2565. PMID: 17855378, DOI: 10.1093/brain/awm202.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsApoptosisCerebral CortexDisease Models, AnimalFemaleHumansIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsMiddle AgedMotor CortexMultiple SclerosisMyelin SheathNerve RegenerationNerve Tissue ProteinsNeurogliaNeuronsRatsRats, WistarRNA, MessengerSemaphorin-3ASignal TransductionUp-RegulationConceptsMultiple sclerosisSemaphorin 3AAbility of plaqueActive demyelinating lesionsNeuronal cell bodiesFailure of repairCentral nervous systemOligodendrocyte precursor cellsOligodendrocyte precursor cell migrationPrecursor cell migrationChronic plaquesDemyelinating lesionsDemyelinated plaquesMyelin repairDemyelinated axonsMS tissueNervous systemCell bodiesExperimental modelPlaquesLesionsPrecursor cellsSclerosisOligodendroglial migrationCell migration
2001
Sonic hedgehog-dependent emergence of oligodendrocytes in the telencephalon: evidence for a source of oligodendrocytes in the olfactory bulb that is independent of PDGFRalpha signaling.
Spassky N, Heydon K, Mangatal A, Jankovski A, Olivier C, Queraud-Lesaux F, Goujet-Zalc C, Thomas J, Zalc B. Sonic hedgehog-dependent emergence of oligodendrocytes in the telencephalon: evidence for a source of oligodendrocytes in the olfactory bulb that is independent of PDGFRalpha signaling. Development 2001, 128: 4993-5004. PMID: 11748136, DOI: 10.1242/dev.128.24.4993.Peer-Reviewed Original ResearchConceptsSpinal cordPlatelet-derived growth factor receptorOlfactory bulbOligodendrocyte progenitorsInduction of oligodendrocytesSource of oligodendrocytesAnterior entopeduncular areaMedial ganglionic eminenceExpression of PLPGrowth factor receptorRostral palliumTelencephalic oligodendrocytesGanglionic eminenceVentricular focusOligodendroglial lineageCordRostral telencephalonOligodendrocytesOligodendrocyte lineageFactor receptorVentricular progenitorsTelencephalonMouse telencephalonSonic hedgehogMolecular mechanisms