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
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