Featured Publications
Cell-Extracellular Matrix Interactions Play Multiple Essential Roles in Aortic Arch Development
Warkala M, Chen D, Ramirez A, Jubran A, Schonning M, Wang X, Zhao H, Astrof S. Cell-Extracellular Matrix Interactions Play Multiple Essential Roles in Aortic Arch Development. Circulation Research 2020, 128: e27-e44. PMID: 33249995, PMCID: PMC7864893, DOI: 10.1161/circresaha.120.318200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicCell LineageCell-Matrix JunctionsEndothelial Progenitor CellsExtracellular MatrixExtracellular Matrix ProteinsFibronectinsGene Expression Regulation, DevelopmentalGestational AgeIntegrin alpha5beta1LIM-Homeodomain ProteinsMice, 129 StrainMice, Inbred C57BLMice, KnockoutMorphogenesisSignal TransductionTranscription FactorsConceptsSecond heart fieldPharyngeal arch arteriesCell-ECM interactionsPAA formationAortic arch arteriesPharyngeal archesArch arteriesIntegrin α5β1Whole-mount confocal imagingEssential roleCell-extracellular matrix interactionsFourth pharyngeal arch arteryMultiple essential rolesEndothelial cell dynamicsNeural crest-derived cellsCrest-derived cellsLethal birth defectEC progenitorsUnderstanding genesHeart fieldLineage tracingVascular smooth muscle cellsMorphogenesisAortic arch developmentDevelopmental stagesEmerging roles of PLCγ1 in endothelial biology
Chen D, Simons M. Emerging roles of PLCγ1 in endothelial biology. Science Signaling 2021, 14 PMID: 34344833, PMCID: PMC8507396, DOI: 10.1126/scisignal.abc6612.Peer-Reviewed Original ResearchConceptsUnique protein structurePhospholipase C-γ1Receptor tyrosine kinasesRole of PLCγ1Major physiological roleMolecular functionsDistinct vascular phenotypePLC familyC-γ1Signal transducerProtein structureDirect effectorTyrosine kinaseMembrane lipidsSecond messengerFunction mutationsPhysiological rolePLCγ1Endothelial biologyEndothelial cancerCritical roleVascular phenotypeEndothelial cellsKinaseFuture investigationsEndothelium in the pharyngeal arches 3, 4 and 6 is derived from the second heart field
Wang X, Chen D, Chen K, Jubran A, Ramirez A, Astrof S. Endothelium in the pharyngeal arches 3, 4 and 6 is derived from the second heart field. Developmental Biology 2016, 421: 108-117. PMID: 27955943, PMCID: PMC5221477, DOI: 10.1016/j.ydbio.2016.12.010.Peer-Reviewed Original ResearchFibronectin signals through integrin α5β1 to regulate cardiovascular development in a cell type-specific manner
Chen D, Wang X, Liang D, Gordon J, Mittal A, Manley N, Degenhardt K, Astrof S. Fibronectin signals through integrin α5β1 to regulate cardiovascular development in a cell type-specific manner. Developmental Biology 2015, 407: 195-210. PMID: 26434918, PMCID: PMC5312697, DOI: 10.1016/j.ydbio.2015.09.016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBranchial RegionCardiovascular SystemCell LineageEmbryo, MammalianFemaleFibronectinsIntegrin alpha5beta1LIM-Homeodomain ProteinsMice, KnockoutModels, BiologicalMorphogenesisMutationNeural CrestOrgan SpecificityPharynxPhenotypePregnancySignal TransductionStem CellsT-Box Domain ProteinsThymus GlandTranscription FactorsConceptsPharyngeal arch arteriesCardiovascular developmentIntegrin α5Pharyngeal arch mesodermCell type-specific mannerCell typesMid-gestation lethalityType-specific mannerDistinct cell typesCardiac outflow tractMorphogenetic defectsPharyngeal regionMouse embryogenesisConditional mutantsExtracellular matrix glycoproteinEmbryonic developmentMutagenesis studiesCardiovascular morphogenesisNeural crestPAA formationSurface ectodermDefective formationArch arteriesFN1Matrix glycoprotein
2023
Endothelial VEGFR2-PLCγ signaling regulates vascular permeability and anti-tumor immunity through eNOS/Src
Sjöberg E, Melssen M, Richards M, Ding Y, Chanoca C, Chen D, Nwadozi E, Pal S, Love D, Ninchoji T, Shibuya M, Simons M, Dimberg A, Claesson-Welsh L. Endothelial VEGFR2-PLCγ signaling regulates vascular permeability and anti-tumor immunity through eNOS/Src. Journal Of Clinical Investigation 2023, 133: e161366. PMID: 37651195, PMCID: PMC10575733, DOI: 10.1172/jci161366.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseRenal cell carcinomaAnti-tumor immunityVascular leakageT cellsEndothelial barrierClear cell renal cell carcinomaCell renal cell carcinomaRegulatory T cellsHelper T cellsNitric oxide synthaseImmune cell activationAntitumor immunityImmunosuppressive cytokinesPoor prognosisCell carcinomaPLCγ pathwayOxide synthaseVascular permeabilityB cellsActivation of PLCγCell activationTumor vesselsDecreased expressionCancer formsChylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption
Zarkada G, Chen X, Zhou X, Lange M, Zeng L, Lv W, Zhang X, Li Y, Zhou W, Liu K, Chen D, Ricard N, Liao J, Kim Y, Benedito R, Claesson-Welsh L, Alitalo K, Simons M, Ju R, Li X, Eichmann A, Zhang F. Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption. Circulation Research 2023, 133: 333-349. PMID: 37462027, PMCID: PMC10530007, DOI: 10.1161/circresaha.123.322607.Peer-Reviewed Original ResearchConceptsLymphatic endothelial cellsCell-cell junctionsCytoskeleton contractionMolecular biology approachesSmall GTPase Rac1Cytoskeletal contractilityBiology approachGTPase Rac1Stress fibersA SignalingPI3KLipid uptakePermeability regulationLymphatic permeabilityIntestinal lipid absorptionLEC junctionJunction openingEndothelial cellsLymphatic capillariesVEGFR-2Fundamental mechanismsLymphatic barrierLymphatic vesselsVascular endothelial growthLymphatic junctions
2019
FRS2α-dependent cell fate transition during endocardial cushion morphogenesis
Chen D, Zhu X, Kofler N, Wang Y, Zhou B, Simons M. FRS2α-dependent cell fate transition during endocardial cushion morphogenesis. Developmental Biology 2019, 458: 88-97. PMID: 31669335, DOI: 10.1016/j.ydbio.2019.10.022.Peer-Reviewed Original ResearchConceptsCell fate transitionsFate transitionsAtrioventricular valve developmentInducible endothelial-specific deletionPivotal controllerEmbryonic developmentEndothelial-specific deletionFRS2αValve developmentEndocardial cushionsEndocardial cellsMesenchymal transitionMesenchymal cellsAV cushionsDefective maturationDevelopmental abnormalitiesDeletionAdult endotheliumN-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA165-dependent neovascularization
Corti F, Wang Y, Rhodes JM, Atri D, Archer-Hartmann S, Zhang J, Zhuang ZW, Chen D, Wang T, Wang Z, Azadi P, Simons M. N-terminal syndecan-2 domain selectively enhances 6-O heparan sulfate chains sulfation and promotes VEGFA165-dependent neovascularization. Nature Communications 2019, 10: 1562. PMID: 30952866, PMCID: PMC6450910, DOI: 10.1038/s41467-019-09605-z.Peer-Reviewed Original Research