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 diseasesA Designed Zinc-finger Transcriptional Repressor of Phospholamban Improves Function of the Failing Heart
Zhang HS, Liu D, Huang Y, Schmidt S, Hickey R, Guschin D, Su H, Jovin IS, Kunis M, Hinkley S, Liang Y, Hinh L, Spratt SK, Case CC, Rebar EJ, Ehrlich BE, Ehrlich B, Gregory P, Giordano F. A Designed Zinc-finger Transcriptional Repressor of Phospholamban Improves Function of the Failing Heart. Molecular Therapy 2012, 20: 1508-1515. PMID: 22828502, PMCID: PMC3412484, DOI: 10.1038/mt.2012.80.Peer-Reviewed Original ResearchConceptsHeart failureZinc finger protein transcription factorsSingle gene regulationZinc finger transcriptional repressorDiverse DNA sequencesProtein transcription factorsDisease-related genesDisease-related proteinsGene repressionZFP TFsTranscriptional repressorTranscription factorsDNA sequencesPotent repressionPLN expressionHuman diseasesRepressorContractile functionDrug targetsFailing HeartTherapeutic inhibitionAnimal modelsReuptake kineticsRepressionTherapeutic interventions
2007
Hypoxia-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 ResearchConceptsHIF-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 propertiesThe Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity*
Luan Y, Yu XP, Xu K, Ding B, Yu J, Huang Y, Yang N, Lengyel P, Di Cesare PE, Liu CJ. The Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity*. Journal Of Biological Chemistry 2007, 282: 16860-16870. PMID: 17439944, DOI: 10.1074/jbc.m610943200.Peer-Reviewed Original ResearchConceptsGene activationTranscription factorsRetinoblastoma proteinProtein-protein interactionsChromatin immunoprecipitation assaysMesenchymal cell lineSkeletal muscle myotubesP204 expressionP204 proteinCore-binding factor alpha1Numerous proteinsImmunoprecipitation assaysSuch mutantsOsteocalcin geneReporter geneGene expressionAntisense RNAMuscle myotubesOsteoblast differentiationCbfa1Factor alpha1ProteinEssential mediatorTernary complexCell lines
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 cellsp204 Is Required for the Differentiation of P19 Murine Embryonal Carcinoma Cells to Beating Cardiac Myocytes ITS EXPRESSION IS ACTIVATED BY THE CARDIAC GATA4, NKX2.5, AND TBX5 PROTEINS*
Ding B, Liu CJ, Huang Y, Hickey RP, Yu J, Kong W, Lengyel P. p204 Is Required for the Differentiation of P19 Murine Embryonal Carcinoma Cells to Beating Cardiac Myocytes ITS EXPRESSION IS ACTIVATED BY THE CARDIAC GATA4, NKX2.5, AND TBX5 PROTEINS*. Journal Of Biological Chemistry 2006, 281: 14882-14892. PMID: 16556595, DOI: 10.1074/jbc.m511747200.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCell Line, TumorChromatinGATA4 Transcription FactorGene Expression Regulation, DevelopmentalHomeobox Protein Nkx-2.5Homeodomain ProteinsMiceMolecular Sequence DataMuscle, SkeletalMyocytes, CardiacNuclear ProteinsPhosphoproteinsT-Box Domain ProteinsTranscription FactorsConceptsNuclear export signalExport signalTranscription factorsP19 cellsC2C12 skeletal muscle myoblastsP19 murine embryonal carcinoma cellsEmbryonal carcinoma stem cellsAdult mouse tissuesMurine embryonal carcinoma cellsTBX5 transcription factorSkeletal muscle myoblastsEmbryonal carcinoma cellsCarcinoma stem cellsP204 expressionP204 proteinExpression of GATA4Regulatory regionsTBX5 proteinReporter constructsAntisense RNAMuscle myoblastsCardiac myocytesMouse tissuesStem cellsGATA4
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 model