2012
IL-13 receptor α2-arginase 2 pathway mediates IL-13-induced pulmonary hypertension
Cho WK, Lee CM, Kang MJ, Huang Y, Giordano FJ, Lee PJ, Trow TK, Homer RJ, Sessa WC, Elias JA, Lee CG. IL-13 receptor α2-arginase 2 pathway mediates IL-13-induced pulmonary hypertension. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2012, 304: l112-l124. PMID: 23125252, PMCID: PMC3543640, DOI: 10.1152/ajplung.00101.2012.Peer-Reviewed Original ResearchConceptsPulmonary hypertensionIL-13Human pulmonary artery smooth muscle cellsDevelopment of PHPulmonary artery smooth muscle cellsRight ventricle systolic pressurePathogenesis of PHArtery smooth muscle cellsExpression of ARG2Pulmonary arterial hypertensionPulmonary vascular remodelingVentricle systolic pressurePotential therapeutic targetIL-13 treatmentSmooth muscle cellsNull mutant miceArterial hypertensionEffector cytokinesMedial thickeningSystolic pressureHemodynamic changesPulmonary arterySmall-interfering RNAVascular remodelingArginase-2Engineered 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 interventionsmiR-1 mediated suppression of Sorcin regulates myocardial contractility through modulation of Ca2+ signaling
Ali R, Huang Y, Maher SE, Kim RW, Giordano FJ, Tellides G, Geirsson A. miR-1 mediated suppression of Sorcin regulates myocardial contractility through modulation of Ca2+ signaling. Journal Of Molecular And Cellular Cardiology 2012, 52: 1027-1037. PMID: 22326846, DOI: 10.1016/j.yjmcc.2012.01.020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCalcium SignalingCalcium-Binding ProteinsCardiac VolumeCardiomyopathiesCell LineDEAD-box RNA HelicasesHeartHumansMaleMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutMicroRNAsMyocardial ContractionMyocardiumRibonuclease IIIRNA InterferenceRNA, Small InterferingUp-RegulationConceptsCardiac functionMiR-1Normal cardiac contractile functionEnd-stage cardiomyopathyCardiac contractile functionWild-type miceCalcium signalingExcitation-contraction couplingModulation of Ca2Cultured mouse cardiomyocytesAcute cardiomyopathyMiR-1 targetsHeart failureMyocardial contractilityMiR-1 knockdownContractile functionAntagomir treatmentSorcin expressionCalcium homeostasisKnockdown miceSorcin levelsCardiac phenotypeMouse cardiomyocytesCritical mediatorPathological relevance
2010
Cellular Endocytosis and Gene Delivery
Ziello J, Huang Y, Jovin I. Cellular Endocytosis and Gene Delivery. Molecular Medicine 2010, 16: 222-229. PMID: 20454523, PMCID: PMC2864810, DOI: 10.2119/molmed.2009.00101.Peer-Reviewed Original ResearchConceptsGene therapyNonviral vectorsClathrin-independent endocytic processVariety of vectorsUnderstanding of endocytosisClathrin-dependent endocytosisCurrent molecular medicineMechanism of endocytosisGene deliveryLipid raftsEndocytic processVector deliveryCellular traffickingCellular endocytosisEndocytosisMolecular medicineTraffickingTarget cellsCellsMetabolic diseasesTherapeutic potentialCaveolaeGenesDeliveryAdeno
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 properties