2025
Reduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling
Zhu Y, Mehlkop O, Backes H, Cremer A, Porniece M, Klemm P, Steuernagel L, Chen W, Johnen R, Wunderlich F, Jais A, Brüning J. Reduced Notch signaling in hypothalamic endothelial cells mediates obesity-induced alterations in glucose uptake and insulin signaling. Cell Reports 2025, 44: 115522. PMID: 40186867, DOI: 10.1016/j.celrep.2025.115522.Peer-Reviewed Original ResearchConceptsShort-term HFD feedingNotch signalingIntracellular domainGlucose uptakeBrain microvascular endothelial cellsNotch intracellular domainHFD feedingDownregulation of Notch signalingHigh-fat dietBlood-brain barrierReduced Notch signalingGLUT1 expressionInsulin signalingSystemic insulin sensitivityBlood-brain barrier permeabilityNotch activationInduced expressionObesity-induced alterationsCaveolae formationPleiotropic effectsEndothelial cellsMicrovascular endothelial cellsExpressionBlood-brain barrier functionCultured brain microvascular endothelial cells
2024
Notch 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
2020
Combinatorial ETS1-Dependent Control of Oncogenic NOTCH1 Enhancers in T-cell LeukemiaETS1-Dependent Control of Notch Transcriptional Programs
McCarter A, Della Gatta G, Melnick A, Kim E, Sha C, Wang Q, Nalamolu J, Liu Y, Keeley T, Yan R, Sun M, Kodgule R, Kunnath N, Ambesi-Impiombato A, Kuick R, Rao A, Ryan R, Kee B, Samuelson L, Ostrowski M, Ferrando A, Chiang M. Combinatorial ETS1-Dependent Control of Oncogenic NOTCH1 Enhancers in T-cell LeukemiaETS1-Dependent Control of Notch Transcriptional Programs. Blood Cancer Discovery 2020, 1: 178-197. PMID: 32924017, PMCID: PMC7482717, DOI: 10.1158/2643-3230.bcd-20-0026.Peer-Reviewed Original ResearchConceptsT-cell acute lymphoblastic leukemiaPan-Notch inhibitorsT cellsNotch-responsive elementsT cell developmentTranscription complexGenetic approachesTranscriptional elementsT-cell transcription factorsTranscription factorsTranscriptional programsAnti-Notch therapiesResponse elementNotch activationAcute lymphoblastic leukemiaEffector pathwaysETS1Lymphoblastic leukemiaProfiling studiesIntestinal toxicityMouse modelIntestinal effectsTreat cancerAdverse effectsSuppressive effect
2019
Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition
Augert A, Eastwood E, Ibrahim A, Wu N, Grunblatt E, Basom R, Liggitt D, Eaton K, Martins R, Poirier J, Rudin C, Milletti F, Cheng W, Mack F, MacPherson D. Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition. Science Signaling 2019, 12 PMID: 30723171, PMCID: PMC6530478, DOI: 10.1126/scisignal.aau2922.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic Helix-Loop-Helix Transcription FactorsCell Line, TumorEnzyme InhibitorsGene Expression Regulation, NeoplasticHistone DemethylasesHumansKaplan-Meier EstimateLung NeoplasmsMice, Inbred NODMice, KnockoutMice, SCIDReceptors, NotchSignal TransductionSmall Cell Lung CarcinomaTumor BurdenXenograft Model Antitumor AssaysConceptsSmall cell lung cancerCell lung cancerNonsmall cell lung cancerLung cancerNotch activationLSD1 inhibitionPatient-derived xenograft modelsLSD1 inhibitorsReactivation of NotchFirst-line standardExpression of Ascl1Durable tumor regressionTranscription factor Ascl1Notch pathway activationLineage genesKnockdown studiesNotch pathwayDownstream signalingCare treatmentPDX modelsTumor regressionTargeted therapySCLC tumorigenesisActionable mutationsXenograft model
2017
Endothelial Notch signalling limits angiogenesis via control of artery formation
Hasan SS, Tsaryk R, Lange M, Wisniewski L, Moore JC, Lawson ND, Wojciechowska K, Schnittler H, Siekmann AF. Endothelial Notch signalling limits angiogenesis via control of artery formation. Nature Cell Biology 2017, 19: 928-940. PMID: 28714969, PMCID: PMC5534340, DOI: 10.1038/ncb3574.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedArteriesCell MovementCells, CulturedEndothelial CellsGene Expression Regulation, DevelopmentalGenotypeHomeodomain ProteinsHuman Umbilical Vein Endothelial CellsHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMicroscopy, FluorescenceMicroscopy, VideoNeovascularization, PhysiologicNerve Tissue ProteinsPhenotypeReceptor, Notch1Receptors, CXCR4Signal TransductionTime FactorsTime-Lapse ImagingTransfectionZebrafishZebrafish ProteinsConceptsNotch signalingTip cellsBlood vessel growthChemokine receptor cxcr4aTip cell migrationArtery formationNotch ligand DLL4Role of NotchVessel growthStalk cellsNotch activationAngiogenic sproutingLigand DLL4Endothelial NotchCell migrationSignalingPlexus formationBlood flow patternsAngiogenesisArterial circulationCellsNotchExpressionCxcr4aZebrafish
2016
Anabolic actions of Notch on mature bone
Liu P, Ping Y, Ma M, Zhang D, Liu C, Zaidi S, Gao S, Ji Y, Lou F, Yu F, Lu P, Stachnik A, Bai M, Wei C, Zhang L, Wang K, Chen R, New M, Rowe D, Yuen T, Sun L, Zaidi M. Anabolic actions of Notch on mature bone. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e2152-e2161. PMID: 27036007, PMCID: PMC4839423, DOI: 10.1073/pnas.1603399113.Peer-Reviewed Original ResearchConceptsOvariectomy-induced bone lossEGFP reporter miceStimulation of NotchBone lossAnabolic actionAnabolic responseReporter miceMature micePresenilin 1Bone healingLigand Jagged1Bone formationTime pointsMiceAdult boneGenetic disruptionMature boneBone matrixConditional activationNotch expressionTerminal osteoblast differentiationNotch activationOsteoblast differentiationBoneOsteocytes
2013
Notching up on the cellular origins of intrahepatic cholangiocarcinoma
Sirica A, Groszmann R, Iwakiri Y, Taddei T. Notching up on the cellular origins of intrahepatic cholangiocarcinoma. Hepatology 2013, 57: 1668-1671. PMID: 23390051, DOI: 10.1002/hep.26313.Peer-Reviewed Original ResearchOrigin of intrahepatic cholangiocarcinomaBiliary lineage cellsLiver progenitor cellsBiliary epithelial cellsIntrahepatic cholangiocarcinomaCell type-specific reportersMouse modelLineage cellsCellular originMouse model of intrahepatic cholangiocarcinomaPrimary liver tumorsActivated NotchDevelopment of effective therapiesNotch activationAkt signalingLiver cell typesCell typesRefractory diseasePrimary malignancyPoor prognosisViral hepatitisLiver tumorsMalignant tumorsEffective therapyProgenitor cells
2012
Notch Signaling Inhibits Axon Regeneration
Bejjani R, Hammarlund M. Notch Signaling Inhibits Axon Regeneration. Neuron 2012, 73: 268-278. PMID: 22284182, PMCID: PMC3690129, DOI: 10.1016/j.neuron.2011.11.017.Peer-Reviewed Original Research
2009
Embryonic arrest at midgestation and disruption of Notch signaling produced by the absence of both epsin 1 and epsin 2 in mice
Chen H, Ko G, Zatti A, Di Giacomo G, Liu L, Raiteri E, Perucco E, Collesi C, Min W, Zeiss C, De Camilli P, Cremona O. Embryonic arrest at midgestation and disruption of Notch signaling produced by the absence of both epsin 1 and epsin 2 in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 13838-13843. PMID: 19666558, PMCID: PMC2728981, DOI: 10.1073/pnas.0907008106.Peer-Reviewed Original ResearchConceptsEndocytic adaptorsRole of epsinsClathrin-mediated endocytosisSpecific membrane proteinsDouble knockout embryosPrimary target genesBeginning of organogenesisActivation of NotchEmbryonic lethalityPutative functionsKnockout embryosEmbryonic arrestMembrane proteinsGenetic approachesTarget genesDKO embryosNotch activationNotch signalingEndocytic functionDevelopmental defectsGenesEpsinEmbryosInactivation resultsEndocytosis
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