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 antibodiesNotch signaling regulates UNC5B to suppress endothelial proliferation, migration, junction activity, and retinal plexus branching
Raza Q, Nadeem T, Youn S, Swaminathan B, Gupta A, Sargis T, Du J, Cuervo H, Eichmann A, Ackerman S, Naiche L, Kitajewski J. Notch signaling regulates UNC5B to suppress endothelial proliferation, migration, junction activity, and retinal plexus branching. Scientific Reports 2024, 14: 13603. PMID: 38866944, PMCID: PMC11169293, DOI: 10.1038/s41598-024-64375-z.Peer-Reviewed Original ResearchConceptsNotch signalingEndothelial cell behaviorEndothelial junctionsCell behaviorMultiple endothelial cell typesStabilization of endothelial junctionsNotch activationEndothelial Notch signalingTarget of Notch signalingTranscriptional activation complexEndothelial cell typesPlexus branchesVascular densityEndothelial proliferationBrain endotheliumMouse retinaIn vivo targetingEffector proteinsVascular outgrowthJunction activityNotch proteinsEndothelial cellsExcessive vascularizationDownstream effectorsEndothelial gene expression
2022
Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas
Zhang H, Li B, Huang Q, López-Giráldez F, Tanaka Y, Lin Q, Mehta S, Wang G, Graham M, Liu X, Park I, Eichmann A, Min W, Zhou J. Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas. Nature Communications 2022, 13: 7637. PMID: 36496409, PMCID: PMC9741628, DOI: 10.1038/s41467-022-35262-w.Peer-Reviewed Original ResearchConceptsMitochondrial dysfunctionThioredoxin 2Single-cell RNA-seq analysisRNA-seq analysisMutant miceNuclear genesMitochondrial proteinsMitochondrial localizationHuman retinal diseasesTranscriptional factorsGene expressionMutant retinasMitochondrial activityExtracellular matrixNovel mechanismVascular maturationArteriovenous malformationsGenetic deficiencyVessel growthSmad2Mouse retinaVascular malformationsMechanistic studiesBasement membraneRetinal vascular malformations
2021
Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron Development
Li J, Geraldo LH, Dubrac A, Zarkada G, Eichmann A. Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron Development. Journal Of The American Society Of Nephrology 2021, 32: 2255-2272. PMID: 34341180, PMCID: PMC8729857, DOI: 10.1681/asn.2020111640.Peer-Reviewed Original ResearchConceptsGlomerular vascularizationRobo receptorsKidney functionVascular developmentGlomerular perfusionKidney diseaseGlomerular endotheliumLigand trapInhibited vascularizationSlit2-RoboEndothelial proliferationGlomerular capillariesEndothelial compartmentGlomerular angiogenesisPerfusion analysisKidney vasculatureVascularizationUreteric bud branchingNovel roleAxon guidanceNephron developmentBlood filtrationReceptorsAngiogenesisGene deletion
2012
ALK1 Signaling Inhibits Angiogenesis by Cooperating with the Notch Pathway
Larrivée B, Prahst C, Gordon E, del Toro R, Mathivet T, Duarte A, Simons M, Eichmann A. ALK1 Signaling Inhibits Angiogenesis by Cooperating with the Notch Pathway. Developmental Cell 2012, 22: 489-500. PMID: 22421041, PMCID: PMC4047762, DOI: 10.1016/j.devcel.2012.02.005.Peer-Reviewed Original ResearchMeSH KeywordsActivin Receptors, Type IActivin Receptors, Type IIAnimalsArteriovenous MalformationsBasic Helix-Loop-Helix Transcription FactorsCell Cycle ProteinsDipeptidesDisease Models, AnimalGrowth Differentiation Factor 2Growth Differentiation FactorsHumansMiceMice, Inbred C57BLNeovascularization, PhysiologicReceptors, NotchRepressor ProteinsRetinaSignal TransductionSmad ProteinsTelangiectasia, Hereditary HemorrhagicVascular Endothelial Growth FactorsConceptsActivin receptor-like kinase 1Hereditary hemorrhagic telangiectasiaArteriovenous malformationsActivation of ALK1Receptor-like kinase 1Notch pathwayVascular lesionsHemorrhagic telangiectasiaPostnatal developmentInhibits angiogenesisNotch inhibitionTip cell formationReceptor familyAngiogenesisHypervascularizationALK1Kinase 1Cell formationEndothelial sproutingPatients
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
The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching
Suchting S, Freitas C, le Noble F, Benedito R, Bréant C, Duarte A, Eichmann A. The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 3225-3230. PMID: 17296941, PMCID: PMC1805603, DOI: 10.1073/pnas.0611177104.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmyloid Precursor Protein SecretasesAnimalsCalcium-Binding ProteinsEndothelium, VascularGamma-Aminobutyric AcidImmunohistochemistryIn Situ HybridizationIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceMice, Mutant StrainsReceptors, Vascular Endothelial Growth FactorRetinal VesselsSignal TransductionTriglyceridesVascular Endothelial Growth Factor AConceptsTip cell formationEndothelial tip cell formationTip cellsNotch ligand DeltaCell formationCell marker genesEndothelial tip cellsVessel branchingLigand DeltaExpression of Dll4Vascular network formationTransmembrane ligandsNotch receptorsMarker genesNegative regulatorAngiogenic sproutingVEGF receptor 2VEGF stimulationFilopodia extensionGamma-secretase inhibitorsGrowth factor VEGFVascular sproutingPharmacological inhibitionDll4Heterozygous deletion
2004
Retinoic acid controls blood vessel formation by modulating endothelial and mural cell interaction via suppression of Tie2 signaling in vascular progenitor cells
Suzuki Y, Komi Y, Ashino H, Yamashita J, Inoue J, Yoshiki A, Eichmann A, Amanuma H, Kojima S. Retinoic acid controls blood vessel formation by modulating endothelial and mural cell interaction via suppression of Tie2 signaling in vascular progenitor cells. Blood 2004, 104: 166-169. PMID: 15026310, DOI: 10.1182/blood-2003-09-3293.Peer-Reviewed Original ResearchConceptsVascular progenitor cellsAll-trans retinoic acidChicken chorioallantoic membraneEndothelial cellsTie2 signalingProgenitor cellsBlood vessel formationMural cellsEpithelial layerExpression of angiopoietin-2Vessel formationRetinoic acidImpaired vascular remodelingImpaired branchingAngiopoietin-2Ang-1Vascular remodelingRo41-5253Cell interactionsMural cell interactions