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 antibodiesIncidence de la circulation lymphatique méningée sur la réponse à un accident vasculaire cérébral
Thomas J, Boisserand L, Kamouh M. Incidence de la circulation lymphatique méningée sur la réponse à un accident vasculaire cérébral. Médecine/sciences 2024, 40: 604-608. PMID: 39303108, DOI: 10.1051/medsci/2024086.Peer-Reviewed Original ResearchMeningeal 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 componentsHeadachePainPathophysiologyDysfunctionMiceElucidating a new path of CSF transport in the CNS
Benveniste H, Thomas J. Elucidating a new path of CSF transport in the CNS. The Lancet Neurology 2024, 23: 553-554. PMID: 38760087, DOI: 10.1016/s1474-4422(24)00164-9.Peer-Reviewed Original Research
2023
Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma
Khang M, Lee J, Lee T, Suh H, Lee S, Cavaliere A, Rushing A, Geraldo L, Belitzky E, Rossano S, de Feyter H, Shin K, Huttner A, Roussel M, Thomas J, Carson R, Marquez-Nostra B, Bindra R, Saltzman W. Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma. Science Translational Medicine 2023, 15: eadi1617. PMID: 37910601, PMCID: PMC11078331, DOI: 10.1126/scitranslmed.adi1617.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidDelivery of drugsEffective therapyTherapeutic indexPARP inhibitorsBlood-brain barrierSite of tumorRapid systemic clearanceXenograft mouse modelSolvent evaporation processAdministration of substancesLeptomeningeal spreadIntrathecal deliveryLeptomeningeal metastasesBrain penetrationSystemic clearanceTumor regressionPolymer nanoparticlesMetastatic medulloblastomaMouse modelPediatric medulloblastomaDrug accumulationCSF turnoverEncapsulated drugsPET imagingCCL21-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 21
2022
CSF-to-dura gateways
Thomas J, Benveniste H. CSF-to-dura gateways. Journal Of Experimental Medicine 2022, 220: e20221719. PMID: 36472584, PMCID: PMC9729850, DOI: 10.1084/jem.20221719.Peer-Reviewed Original ResearchIdentification of growth hormone receptor as a relevant target for precision medicine in low‐EGFR expressing glioblastoma
Verreault M, Vilchis I, Rosenberg S, Lemaire N, Schmitt C, Guehennec J, Royer‐Perron L, Thomas J, Lam TT, Dingli F, Loew D, Ducray F, Paris S, Carpentier C, Marie Y, Laigle‐Donadey F, Rousseau A, Pigat N, Boutillon F, Bielle F, Mokhtari K, Frank SJ, de Reyniès A, Hoang‐Xuan K, Sanson M, Goffin V, Idbaih A. Identification of growth hormone receptor as a relevant target for precision medicine in low‐EGFR expressing glioblastoma. Clinical And Translational Medicine 2022, 12: e939. PMID: 35808822, PMCID: PMC9270581, DOI: 10.1002/ctm2.939.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorGrowth hormone receptorPatient-derived cell linesOncogenic mechanismsGene expression profilesCell linesGain of functionHormone receptorsExpression of proteinsCellular movementGrowth factor receptorHuman GBM samplesExpression profilesCell migrationCommon oncogenic mechanismThird of patientsDistinct molecular subsetsGBM samplesPromoter hypermethylationNew therapeutic approachesFactor receptorCell proliferationPharmacological inhibitionRelevant targetsOverexpressionConserved meningeal lymphatic drainage circuits in mice and humans
Jacob L, de Brito Neto J, Lenck S, Corcy C, Benbelkacem F, Geraldo LH, Xu Y, Thomas JM, Kamouh M, Spajer M, Potier MC, Haik S, Kalamarides M, Stankoff B, Lehericy S, Eichmann A, Thomas JL. Conserved meningeal lymphatic drainage circuits in mice and humans. Journal Of Experimental Medicine 2022, 219: e20220035. PMID: 35776089, PMCID: PMC9253621, DOI: 10.1084/jem.20220035.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidVessel wall magnetic resonance imagingDural venous sinusesMagnetic resonance imagingCavernous sinusSystemic injectionImmune surveillanceVenous sinusesGlymphatic systemNeurological diseasesDura materVW-MRIResonance imagingBrain tissueEmissary veinsNeurological pathologiesAnterior partCSF outflowTracer injectionDrainage circuitThree-dimensional anatomyLymphatic vesselsPatientsDiagnostic toolSinus
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 1Neuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2020
Les vaisseaux lymphatiques méningés, une cible potentielle pour le traitement des tumeurs cérébrales
Thomas JL, Song E, Boisserand L, Iwasaki A. Les vaisseaux lymphatiques méningés, une cible potentielle pour le traitement des tumeurs cérébrales. Médecine/sciences 2020, 36: 709-713. PMID: 32821046, PMCID: PMC8158397, DOI: 10.1051/medsci/2020141.Peer-Reviewed Original ResearchThree-Dimensional Imaging of the Vertebral Lymphatic Vasculature and Drainage using iDISCO+ and Light Sheet Fluorescence Microscopy.
Jacob L, Brito J, Thomas JL. Three-Dimensional Imaging of the Vertebral Lymphatic Vasculature and Drainage using iDISCO+ and Light Sheet Fluorescence Microscopy. Journal Of Visualized Experiments 2020 PMID: 32510513, DOI: 10.3791/61099.Peer-Reviewed Original ResearchConceptsLight sheet fluorescence microscopySheet fluorescence microscopyLymphatic vasculatureFluorescence microscopyCentral nervous systemLymphatic vesselsBiologyLymphatic systemLymphatic networkJoint biologyWhole-mount preparationsUnprecedented opportunityImmune surveillanceNervous systemImmune cellsTissueMount preparationsVertebral columnCNS tissueCellsMagnaMacromoleculesWhole-Genome and RNA Sequencing Reveal Variation and Transcriptomic Coordination in the Developing Human Prefrontal Cortex
Werling DM, Pochareddy S, Choi J, An JY, Sheppard B, Peng M, Li Z, Dastmalchi C, Santpere G, Sousa AMM, Tebbenkamp ATN, Kaur N, Gulden FO, Breen MS, Liang L, Gilson MC, Zhao X, Dong S, Klei L, Cicek AE, Buxbaum JD, Adle-Biassette H, Thomas JL, Aldinger KA, O’Day D, Glass IA, Zaitlen NA, Talkowski ME, Roeder K, State MW, Devlin B, Sanders SJ, Sestan N. Whole-Genome and RNA Sequencing Reveal Variation and Transcriptomic Coordination in the Developing Human Prefrontal Cortex. Cell Reports 2020, 31: 107489. PMID: 32268104, PMCID: PMC7295160, DOI: 10.1016/j.celrep.2020.03.053.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBrainComputational BiologyDatabases, GeneticExome SequencingGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyGenomicsHumansPhenotypePolymorphism, Single NucleotidePrefrontal CortexQuantitative Trait LociSequence Analysis, RNATranscriptomeWhole Genome SequencingConceptsExpression levelsGene expression levelsTranscriptomic coordinationDisorder lociNeuropsychiatric traitsSpecific genesRisk lociGene expressionGenomic variantsDevelopmental stagesCell typesGenesLociTissue RNACommon variantsPostnatal stagesUnique resourceSpecific variantsExpressionEQTLsVariantsGenomeHuman prefrontal cortexRNATraitsVEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours
Song E, Mao T, Dong H, Boisserand LSB, Antila S, Bosenberg M, Alitalo K, Thomas JL, Iwasaki A. VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours. Nature 2020, 577: 689-694. PMID: 31942068, PMCID: PMC7100608, DOI: 10.1038/s41586-019-1912-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain NeoplasmsCD8-Positive T-LymphocytesCell Cycle CheckpointsCell Line, TumorCell MovementCentral Nervous SystemCross-PrimingFemaleGlioblastomaHEK293 CellsHumansImmunologic MemoryImmunologic SurveillanceLymph NodesLymphangiogenesisLymphatic VesselsMaleMelanomaMeningesMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorVascular Endothelial Growth Factor CConceptsCD8 T cellsCentral nervous systemT cellsImmune responseBrain tumorsImmune surveillanceLymphatic drainageNervous systemAntigen-specific immune responsesDeep cervical lymph nodesCapacity of VEGFCervical lymph nodesCheckpoint blockade therapyMeningeal lymphatic systemVascular endothelial growth factor CNew therapeutic approachesUncontrolled tumor growthMeningeal lymphatic vasculatureBlockade therapyLymph nodesTherapeutic approachesMouse modelTumor growthMemory responsesTumors
2019
RNA Profiling of the Human and Mouse Spinal Cord Stem Cell Niches Reveals an Embryonic-like Regionalization with MSX1+ Roof-Plate-Derived Cells
Ghazale H, Ripoll C, Leventoux N, Jacob L, Azar S, Mamaeva D, Glasson Y, Calvo CF, Thomas JL, Meneceur S, Lallemand Y, Rigau V, Perrin FE, Noristani HN, Rocamonde B, Huillard E, Bauchet L, Hugnot JP. RNA Profiling of the Human and Mouse Spinal Cord Stem Cell Niches Reveals an Embryonic-like Regionalization with MSX1+ Roof-Plate-Derived Cells. Stem Cell Reports 2019, 12: 1159-1177. PMID: 31031189, PMCID: PMC6524006, DOI: 10.1016/j.stemcr.2019.04.001.Peer-Reviewed Original ResearchConceptsTranscription factorsRNA profilingDevelopmental transcription factorsDorsal-ventral patternStem cell nicheEpendymal zoneMolecular resourcesMammalian lesionsConserved expressionCell nicheNeural stem cellsCell diversityPossible endogenous sourceQuiescent cellsGenesFloor plateStem cellsMsx1Endogenous sourcesTransgenic miceCellsProfilingSpinal cordCentral canalExpressionLymphatic system in central nervous system
Thomas JL, Jacob L, Boisserand L. Lymphatic system in central nervous system. Médecine/sciences 2019, 35: 55-61. PMID: 30672459, DOI: 10.1051/medsci/2018309.Peer-Reviewed Original ResearchConceptsCentral nervous systemCerebrospinal fluidImmune surveyNervous systemLymphatic vesselsLymphatic systemBrain interstitial fluidHuman CNS diseasesNew therapeutic targetsPeripheral lymphatic systemInterstitial fluid drainageCerebral drainageMeningeal lymphatic vasculatureInterstitial fluidCNS diseaseFluid drainageTherapeutic targetPerivascular spacesTissue drainageConsiderable metabolic activityVasculatureDrainageVesselsMetabolic activityLymphatic vasculature
2018
Adult Human Hippocampus: No New Neurons in Sight
Arellano JI, Harding B, Thomas JL. Adult Human Hippocampus: No New Neurons in Sight. Cerebral Cortex 2018, 28: 2479-2481. PMID: 29746611, DOI: 10.1093/cercor/bhy106.Peer-Reviewed Original Research
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-3Modulation of Endothelial Bone Morphogenetic Protein Receptor Type 2 Activity by Vascular Endothelial Growth Factor Receptor 3 in Pulmonary Arterial Hypertension
Hwangbo C, Lee HW, Kang H, Ju H, Wiley DS, Papangeli I, Han J, Kim JD, Dunworth WP, Hu X, Lee S, El-Hely O, Sofer A, Pak B, Peterson L, Comhair S, Hwang EM, Park JY, Thomas J, Bautch VL, Erzurum SC, Chun HJ, Jin SW. Modulation of Endothelial Bone Morphogenetic Protein Receptor Type 2 Activity by Vascular Endothelial Growth Factor Receptor 3 in Pulmonary Arterial Hypertension. Circulation 2017, 135: 2288-2298. PMID: 28356442, PMCID: PMC5523010, DOI: 10.1161/circulationaha.116.025390.Peer-Reviewed Original ResearchConceptsBMP receptor type 2Vascular endothelial growth factor receptor 3Growth factor receptor 3Zebrafish embryosPulmonary arterial endothelial cellsArterial endothelial cellsVEGFR3 expressionBone morphogenetic protein (BMP) signalingPulmonary arterial hypertensionMorphogenetic protein signalingEndothelial cellsFamilial pulmonary arterial hypertensionBMPR2 functionsPrimary lung endothelial cellsImpaired BMPBMP signalingBMP stimulationProtein signalingReceptor 3Endothelial-specific deletionEctopic angiogenesisKey regulatorHuman endothelial cellsArterial hypertensionLung endothelial cells