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 antibodiesThe glymphatic system as a nexus between obesity and neurological diseases
Chen B, Lenck S, Thomas J, Schneeberger M. The glymphatic system as a nexus between obesity and neurological diseases. Nature Reviews Endocrinology 2024, 1-2. PMID: 39304738, DOI: 10.1038/s41574-024-01042-3.Peer-Reviewed Original ResearchIncidence 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 function promotes oligodendrocyte survival and brain myelination
das Neves S, Delivanoglou N, Ren Y, Cucuzza C, Makuch M, Almeida F, Sanchez G, Barber M, Rego S, Schrader R, Faroqi A, Thomas J, McLean P, Oliveira T, Irani S, Piehl F, Da Mesquita S. Meningeal lymphatic function promotes oligodendrocyte survival and brain myelination. Immunity 2024, 57: 2328-2343.e8. PMID: 39217987, PMCID: PMC11464205, DOI: 10.1016/j.immuni.2024.08.004.Peer-Reviewed Original ResearchLymphatic functionMeningeal lymphatic dysfunctionLymphatic dysfunctionVascular endothelial growth factor-CState of immunosuppressionMyeloid cell activationHuman demyelinating diseasesBrain myelinMature oligodendrocyte numbersClinical relapseImmunocompetent miceAdult miceMeningeal lymphatic functionAxonal lossOligodendrocyte survivalDemyelinating diseaseOligodendrocyte numbersVessel ablationAdaptive immunityCell activationCerebrospinal fluidGene expression changesMature oligodendrocytesOligodendrocyte functionGlial cellsMeningeal 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 ResearchVEGF-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 ResearchEXTH-59. IDENTIFICATION 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 T, 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 S, de Reynies A, Hoang-Xuan K, Sanson M, Goffin V, Idbaih A. EXTH-59. IDENTIFICATION OF GROWTH HORMONE RECEPTOR AS A RELEVANT TARGET FOR PRECISION MEDICINE IN LOW-EGFR EXPRESSING GLIOBLASTOMA. Neuro-Oncology 2023, 25: v237-v237. PMCID: PMC10639947, DOI: 10.1093/neuonc/noad179.0912.Peer-Reviewed Original ResearchGrowth hormone receptorOncogenic mechanismsCommon oncogenic mechanismThird of patientsDistinct molecular subsetsNew therapeutic approachesPromising therapeutic targetHuman GBM samplesPatient-derived cell linesLower eGFRMolecular subsetsExpression of proteinsGBM patientsTherapeutic approachesGlioblastoma patientsTherapeutic targetTumor growthGrowth hormoneEGFR overexpressionPharmacological inhibitionSOCS2 expressionTumor invasionPatientsHormone receptorsGBM samplesIntrathecal 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 21Three-dimensional imaging of vascular development in the mouse epididymis.
Damon-Soubeyrand C, Bongiovanni A, Chorfa A, Goubely C, Pirot N, Pardanaud L, Piboin-Fragner L, Vachias C, Bravard S, Guiton R, Thomas J, Saez F, Kocer A, Tardivel M, Drevet J, Henry-Berger J. Three-dimensional imaging of vascular development in the mouse epididymis. ELife 2023, 12 PMID: 37310207, PMCID: PMC10264076, DOI: 10.7554/elife.82748.Peer-Reviewed Original ResearchConceptsProtection of spermatozoaComplex immune functionsAccessory tubulesVascular developmentMouse epididymisCellular levelSecretory roleImportant playersMale fertilityMale reproductive systemOrgan clearingMature adult miceReproductive systemTransgenic mouse modelFunctional maturationPeripheral toleranceBlood markersImmune responseLymphatic networkImmune functionKey determinantMouse modelSurvival of spermatozoaAdult miceImmune systemConnexin 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
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 ResearchTribute to Klaus Eichmann, Editor-in-Chief of Cellular and Molecular Life Sciences
Thomas J, Bruzzone R, El-Osta A, Claessens F, Ruysschaert J, Wilson D. Tribute to Klaus Eichmann, Editor-in-Chief of Cellular and Molecular Life Sciences. Cellular And Molecular Life Sciences 2022, 79: 529. PMID: 36166158, DOI: 10.1007/s00018-022-04532-7.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 1