2013
Activation of Hypoxia‐Inducible Factor‐2 in Adipocytes Results in Pathological Cardiac Hypertrophy
Lin Q, Huang Y, Booth CJ, Haase VH, Johnson RS, Simon M, Giordano FJ, Yun Z. Activation of Hypoxia‐Inducible Factor‐2 in Adipocytes Results in Pathological Cardiac Hypertrophy. Journal Of The American Heart Association 2013, 2: e000548. PMID: 24326162, PMCID: PMC3886757, DOI: 10.1161/jaha.113.000548.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAnimalsBasic Helix-Loop-Helix Transcription FactorsCardiomegalyCytokinesDisease Models, AnimalGene Expression RegulationGenetic Predisposition to DiseaseHypoxia-Inducible Factor 1, alpha SubunitInflammation MediatorsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMyocytes, CardiacPhenotypeSignal TransductionTime FactorsVon Hippel-Lindau Tumor Suppressor ProteinConceptsPathological cardiac hypertrophyCardiac hypertrophyHypoxia-inducible factor-2Hypoxia-signaling pathwayHypoxia-inducible factor (HIF) pathwayVon Hippel-Lindau (VHL) geneTranscription factorsUncharacterized mechanismAdipose tissueAdipocytes resultsHIF activationObesity-associated cardiomyopathyChemotactic protein-1Protein 1Activated T cellsDirect roleEssential roleCardiomyopathy-associated genesFactor 2Genetic deletionFactor pathwayUndefined mechanismDeletionNuclear factorGenes
2012
Engineered Zinc-Finger Proteins Can Compensate Genetic Haploinsufficiency by Transcriptional Activation of the Wild-Type Allele: Application to Willams-Beuren Syndrome and Supravalvular Aortic Stenosis
Zhang P, Huang A, Morales-Ruiz M, Starcher BC, Huang Y, Sessa WC, Niklason LE, Giordano FJ. Engineered Zinc-Finger Proteins Can Compensate Genetic Haploinsufficiency by Transcriptional Activation of the Wild-Type Allele: Application to Willams-Beuren Syndrome and Supravalvular Aortic Stenosis. Human Gene Therapy 2012, 23: 1186-1199. PMID: 22891920, PMCID: PMC3498887, DOI: 10.1089/hum.2011.201.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAortic Stenosis, SupravalvularCell LineCell MovementCell ProliferationDosage Compensation, GeneticElastinGene ExpressionGene Expression RegulationHaploinsufficiencyHumansMutationNonsense Mediated mRNA DecayOrgan SpecificityProtein EngineeringTranscriptional ActivationWilliams SyndromeZinc FingersConceptsZinc finger protein transcription factorsTranscriptional activationWild-type alleleWilliams-Beuren syndromeMutant allelesEngineered Zinc Finger ProteinsElastin geneTargeted transcriptional activationCompensatory expressionSplice variantsZinc finger proteinProtein transcription factorsNonsense-mediated decayWild-type cellsMultiple splice variantsElastin expressionGene replacement strategyMutant proteinsHaploinsufficient genesTranscription factorsComplex genesNatural stoichiometryDistinct genetic syndromesGenesGenetic diseases
2007
Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice
Murata T, Lin MI, Huang Y, Yu J, Bauer PM, Giordano FJ, Sessa WC. Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice. Journal Of Experimental Medicine 2007, 204: 2373-2382. PMID: 17893196, PMCID: PMC2118452, DOI: 10.1084/jem.20062340.Peer-Reviewed Original ResearchConceptsPulmonary hypertensionRC miceCaveolin-1Endothelial cellsCav-1 KO miceEpithelial cellsCav-1-deficient miceSmooth muscle contractilityEndothelial NO synthase activationNitric oxide productionBronchiolar epithelial cellsNO synthase activationSmooth muscle cellsClear physiological evidenceCaveolin-1 knockout miceLack of rescueCav-1 expressionPulmonary dysfunctionPrincipal structural componentPulmonary arteryPulmonary defectsKO miceMuscle contractilityMyocardial hypertrophyAlveolar hyperplasiaHypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia.
Ziello J, Jovin I, Huang Y. Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. The Yale Journal Of Biology And Medicine 2007, 80: 51-60. PMID: 18160990, PMCID: PMC2140184.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDrug Delivery SystemsGene Expression RegulationHumansHypoxia-Inducible Factor 1IschemiaModels, BiologicalNeoplasmsSignal TransductionConceptsHIF-1HIF-1 pathwayHypoxia-inducible factorDimeric protein complexProtein complexesCrucial physiological regulatorTranscription factorsTarget genesRegulatory pathwaysTranscriptional activityPrimary genesGenesPhysiological regulatorHomeostatic processesVessel proliferationLow oxygen concentrationsPathwayAnaerobic metabolismSmall moleculesCancerous cellsTherapeutic interventionsSpread of cancerProliferationTreatment of diseasesAngiogenic properties
2006
p204 Protein Overcomes the Inhibition of the Differentiation of P19 Murine Embryonal Carcinoma Cells to Beating Cardiac Myocytes by Id Proteins*
Ding B, Liu CJ, Huang Y, Yu J, Kong W, Lengyel P. p204 Protein Overcomes the Inhibition of the Differentiation of P19 Murine Embryonal Carcinoma Cells to Beating Cardiac Myocytes by Id Proteins*. Journal Of Biological Chemistry 2006, 281: 14893-14906. PMID: 16556596, DOI: 10.1074/jbc.m511748200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell Line, TumorFeedback, PhysiologicalGATA4 Transcription FactorGene Expression RegulationHomeobox Protein Nkx-2.5Homeodomain ProteinsInhibitor of Differentiation Protein 1Inhibitor of Differentiation Protein 2Inhibitor of Differentiation ProteinsMiceMyocytes, CardiacNuclear ProteinsPhosphoproteinsTranscription FactorsTranscriptional ActivationConceptsD proteinsP204 proteinP19 cellsP19 murine embryonal carcinoma cellsEmbryonal carcinoma stem cellsNuclear export signalMurine embryonal carcinoma cellsP19 embryonal carcinoma stem cellsCardiac transcription factor GATA4Embryonal carcinoma cellsTranscription factor GATA4Carcinoma stem cellsExport signalSynergistic transactivationTranscription factorsNKX2.5 proteinPositive feedback loopCardiac myocytesDifferentiation proteinGATA4ProteinStem cellsDifferentiationP204Carcinoma cellsAn engineered VEGF‐activating zinc finger protein transcription factor improves blood flow and limb salvage in advanced‐age mice
Yu J, Lei L, Liang Y, Hinh L, Hickey RP, Huang Y, Liu D, Yeh JL, Rebar E, Case C, Spratt K, Sessa WC, Giordano FJ. An engineered VEGF‐activating zinc finger protein transcription factor improves blood flow and limb salvage in advanced‐age mice. The FASEB Journal 2006, 20: 479-481. PMID: 16423874, DOI: 10.1096/fj.04-3670fje.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAgingAmino Acid SequenceAnimalsBlood Flow VelocityFeasibility StudiesGene Expression RegulationGenes, SyntheticGenetic TherapyGenetic VectorsHindlimbIschemiaLaser-Doppler FlowmetryMiceMice, Inbred C57BLMolecular Sequence DataNeovascularization, PhysiologicProtein EngineeringRecombinant ProteinsRNA, MessengerStructure-Activity RelationshipTranscription FactorsVascular Endothelial Growth Factor AZinc FingersConceptsLimb salvageBlood flowHindlimb ischemiaC57/BL6 micePeripheral vascular diseaseVascular endothelial growth factorPotential clinical utilityEndothelial growth factorExpression of VEGFABL6 miceIschemic limbsVascular diseaseIschemic hindlimbMurine modelClinical utilityVessel countProtein transcription factorsGrowth factorProtein levelsSalvage
2004
Stromal Cell–Derived Factor-1α Plays a Critical Role in Stem Cell Recruitment to the Heart After Myocardial Infarction but Is Not Sufficient to Induce Homing in the Absence of Injury
Abbott JD, Huang Y, Liu D, Hickey R, Krause DS, Giordano FJ. Stromal Cell–Derived Factor-1α Plays a Critical Role in Stem Cell Recruitment to the Heart After Myocardial Infarction but Is Not Sufficient to Induce Homing in the Absence of Injury. Circulation 2004, 110: 3300-3305. PMID: 15533866, DOI: 10.1161/01.cir.0000147780.30124.cf.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzylaminesBone Marrow CellsBone Marrow TransplantationCell LineageCell MovementChemokine CXCL12Chemokines, CXCCyclamsFemaleGene Expression ProfilingGene Expression RegulationGenetic TherapyHeterocyclic CompoundsIntercellular Adhesion Molecule-1Matrix Metalloproteinase 9MiceMice, Inbred NODMice, SCIDMyocardial InfarctionMyocardiumReceptors, CXCR4Recombinant Fusion ProteinsStem Cell TransplantationStem CellsTransduction, GeneticVascular Cell Adhesion Molecule-1Vascular Endothelial Growth Factor AConceptsBone marrow-derived cellsStromal cell-derived factor-1alphaMyocardial infarctionBMDC recruitmentAdhesion molecule-1Molecule-1Recruitment of BMDCsInfarcted heartSerum SDF-1 levelsVascular cell adhesion molecule-1Intercellular adhesion molecule-1Stromal cell-derived factor-1αCell adhesion molecule-1Administration of AMD3100SDF-1/CXCR4 interactionMarrow-derived cellsSDF-1 levelsAbsence of MIVascular endothelial growth factorMatrix metalloproteinase-9Sham-operated controlsSDF-1 mRNAEndothelial growth factorAbsence of injuryQuantitative polymerase chain reactionLoss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis
Tang N, Wang L, Esko J, Giordano FJ, Huang Y, Gerber HP, Ferrara N, Johnson RS. Loss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis. Cancer Cell 2004, 6: 485-495. PMID: 15542432, DOI: 10.1016/j.ccr.2004.09.026.Peer-Reviewed Original ResearchAnimalsCell HypoxiaCell ProliferationCells, CulturedChemotaxisEndothelial CellsGene Expression RegulationHypoxia-Inducible Factor 1, alpha SubunitMiceNeoplasmsNeovascularization, PathologicTranscription FactorsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Wound Healing
2002
Induction of angiogenesis in a mouse model using engineered transcription factors
Rebar EJ, Huang Y, Hickey R, Nath AK, Meoli D, Nath S, Chen B, Xu L, Liang Y, Jamieson AC, Zhang L, Spratt SK, Case CC, Wolffe A, Giordano FJ. Induction of angiogenesis in a mouse model using engineered transcription factors. Nature Medicine 2002, 8: 1427-1432. PMID: 12415262, DOI: 10.1038/nm1202-795.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAngiogenesis Inducing AgentsAnimalsDrug DesignGene Expression RegulationGenetic TherapyMiceModels, AnimalMolecular Sequence DataNeovascularization, PhysiologicProtein EngineeringRecombinant ProteinsTranscription FactorsVascular Endothelial Growth Factor AZinc FingersConceptsTranscription factorsEndogenous genesZinc finger protein transcription factorsProtein transcription factorsWhole-organism modelDNA sequencesInduced expressionGenesInduction of angiogenesisZFPExpression of VEGFAProtein VEGFExpressionGrowth factorStimulation of angiogenesisTissue cultureVascular endothelial growth factorExperimental wound healingEndothelial growth factorWound healingNatural arraysAngiogenesisVivoCDNAMouse modelCorticotropin-releasing factor receptor 2 is a tonic suppressor of vascularization
Bale TL, Giordano FJ, Hickey RP, Huang Y, Nath AK, Peterson KL, Vale WW, Lee KF. Corticotropin-releasing factor receptor 2 is a tonic suppressor of vascularization. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 7734-7739. PMID: 12032352, PMCID: PMC124337, DOI: 10.1073/pnas.102187099.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAnimalsCapillariesCell DivisionCells, CulturedEndothelial Growth FactorsEndothelium, VascularGene Expression RegulationLymphokinesMiceMice, KnockoutMuscle, Smooth, VascularNeovascularization, PhysiologicReceptors, Corticotropin-Releasing HormoneVascular Endothelial Growth Factor AVascular Endothelial Growth FactorsConceptsCorticotropin-releasing factor receptor 2Smooth muscle cellsCapillary tube formationTube formationCell cycle progressionVascular endothelial growth factorFactor receptor 2Protein phosphorylationRetinoblastoma proteinCycle progressionLigand activationReceptor 2Adult neovascularizationCRFR2-deficient miceCell proliferationIschemic cardiovascular diseasePotential targetAdult vesselsQuiescent stateMuscle cellsEndothelial growth factorGrowth factorSMC proliferationWestern blotCollagen gels