2014
Pot1a Prevents Telomere Dysfunction and ATM-Dependent Neuronal Loss
Lee Y, Brown EJ, Chang S, McKinnon PJ. Pot1a Prevents Telomere Dysfunction and ATM-Dependent Neuronal Loss. Journal Of Neuroscience 2014, 34: 7836-7844. PMID: 24899707, PMCID: PMC4044246, DOI: 10.1523/jneurosci.4245-13.2014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAtaxia Telangiectasia Mutated ProteinsBeta-GalactosidaseBrainCell CycleCell Cycle ProteinsCells, CulturedDNA DamageDNA-Binding ProteinsEmbryo, MammalianFemaleGene Expression RegulationMaleMiceMice, TransgenicNestinNeuronsShelterin ComplexTelomereTelomere-Binding Proteins
2013
p16INK4a protects against dysfunctional telomere–induced ATR-dependent DNA damage responses
Wang Y, Sharpless N, Chang S. p16INK4a protects against dysfunctional telomere–induced ATR-dependent DNA damage responses. Journal Of Clinical Investigation 2013, 123: 4489-4501. PMID: 24091330, PMCID: PMC3784543, DOI: 10.1172/jci69574.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsApoptosisAtaxia Telangiectasia Mutated ProteinsBone Marrow TransplantationCell ProliferationCells, CulturedCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21DNA DamageDNA RepairDNA-Binding ProteinsFemaleHematopoiesisHematopoietic Stem CellsIntestine, SmallMaleMiceMice, SCIDMice, TransgenicProtein StabilitySequence DeletionSpleenTelomereTelomere HomeostasisTumor Suppressor Protein p53ConceptsHematopoietic cellsDeletion of p21P21-dependent cell cycle arrestOrgan impairmentTelomere dysfunctionCell cycle arrestMouse modelDNA damage responseSmall intestineFunctional defectsCell functionProliferative capacityP53-dependent apoptosisCycle arrestDysfunctional telomeresCellular senescenceDysfunctionP53-dependent DNA damage responseProliferative cellsHematopoietic systemProtective functionTumor suppressorProliferative defectP53 stabilizationCells
2012
Cooperation between p53 and the telomere-protecting shelterin component Pot1a in endometrial carcinogenesis
Akbay EA, Peña CG, Ruder D, Michel JA, Nakada Y, Pathak S, Multani AS, Chang S, Castrillon DH. Cooperation between p53 and the telomere-protecting shelterin component Pot1a in endometrial carcinogenesis. Oncogene 2012, 32: 2211-2219. PMID: 22689059, PMCID: PMC3636499, DOI: 10.1038/onc.2012.232.Peer-Reviewed Original ResearchMeSH KeywordsAneuploidyAnimalsCarcinoma, EndometrioidCell Transformation, NeoplasticDisease Models, AnimalDNA Breaks, Double-StrandedDNA-Binding ProteinsEndometrial NeoplasmsFemaleHumansMiceMice, TransgenicShelterin ComplexTelomere HomeostasisTelomere-Binding ProteinsTumor Cells, CulturedTumor Suppressor Protein p53ConceptsType II endometrial cancerEndometrial intraepithelial carcinomaEndometrial cancerEndometrial adenocarcinomaEndometrial carcinogenesisTelomerase-null miceProminent nuclear atypiaType II tumorsMulti-organ failureType II cancersInvasive endometrial adenocarcinomaMonths of ageMetastatic diseaseII tumorsEndometrial lesionsIntraepithelial carcinomaEndometrial epitheliumNuclear atypiaTumorsAdenocarcinomaVivo correlatesDetectable DNA damageHuman tumorsMiceLesions
2007
Overexpression of the Low Molecular Weight Cyclin E in Transgenic Mice Induces Metastatic Mammary Carcinomas through the Disruption of the ARF-p53 Pathway
Akli S, Van Pelt CS, Bui T, Multani AS, Chang S, Johnson D, Tucker S, Keyomarsi K. Overexpression of the Low Molecular Weight Cyclin E in Transgenic Mice Induces Metastatic Mammary Carcinomas through the Disruption of the ARF-p53 Pathway. Cancer Research 2007, 67: 7212-7222. PMID: 17671189, DOI: 10.1158/0008-5472.can-07-0599.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAnimalsApoptosisBlotting, WesternCyclin ECyclin-Dependent Kinase Inhibitor p16FemaleGene Expression Regulation, NeoplasticGene SilencingHumansImmunoenzyme TechniquesIn Situ Nick-End LabelingLoss of HeterozygosityLung NeoplasmsMammary Neoplasms, ExperimentalMiceMice, KnockoutMice, TransgenicMutationPolymerase Chain ReactionTumor Cells, CulturedTumor Suppressor Protein p53ConceptsFull-length cyclin ECyclin E overexpressionCyclin EARF-p53 pathwayTransgenic miceLow molecular weight cyclin EE overexpressionMetastatic mammary carcinomaMammary tumor formationWeight cyclin ETumor-bearing animalsBreast cancer tumorigenesisBreast cancer cellsMouse mammary tumor virus promoterLow molecular weight isoformsLMW formsOncologic roleInactivation of p53Mammary carcinomaBreast cancerMammary adenocarcinomaLoss of heterozygosityCancer tumorigenesisMammary epithelial cellsMolecular weight isoforms
2005
Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, Rustgi AK, Chang S, Tuveson DA. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005, 7: 469-483. PMID: 15894267, DOI: 10.1016/j.ccr.2005.04.023.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCadherinsCarcinoma, Pancreatic DuctalCentrosomeChromosomal InstabilityChromosome AberrationsCytogenetic AnalysisDisease ProgressionGene ExpressionGene Expression RegulationGene RearrangementGenes, Tumor SuppressorHomeodomain ProteinsIntegrasesMiceMice, Inbred C57BLMice, Inbred StrainsMice, Mutant StrainsMice, TransgenicMutation, MissenseNeoplasm MetastasisOncogene Proteins v-erbBProto-Oncogene Proteins p21(ras)Ras ProteinsSurvival AnalysisTelomereTrans-ActivatorsTranslocation, GeneticTumor Suppressor Protein p53ConceptsPancreatic ductal adenocarcinomaTumor suppressor gene pathwaysDistinct genetic pathwaysGenetic requirementsGenetic pathwaysGenomic instabilityGene pathwaysChromosomal instabilityEndogenous expressionHuman diseasesNonreciprocal translocationsDuctal adenocarcinomaMetastatic pancreatic ductal adenocarcinomaHuman carcinomasDisease pathogenesisMouse pancreasDifferent biological behaviorPathwayMetastatic carcinomaPrimary carcinomaTreatment strategiesCarcinomaBiological behaviorDevelopment of detectionTranslocation
2004
A mouse model of Werner Syndrome: what can it tell us about aging and cancer?
Chang S. A mouse model of Werner Syndrome: what can it tell us about aging and cancer? The International Journal Of Biochemistry & Cell Biology 2004, 37: 991-999. PMID: 15743673, DOI: 10.1016/j.biocel.2004.11.007.Peer-Reviewed Original ResearchMeSH KeywordsAging, PrematureAnimalsDisease Models, AnimalHumansMiceMice, TransgenicNeoplasmsTelomereWerner SyndromeConceptsMolecular mechanismsWerner syndromePremature agingConsequent cellular responsesGene functionMammalian agingDysfunctional telomeresGenetic pathwaysReplicative senescenceTelomere dysfunctionCellular responsesGenetic platformProgeroid syndromesMolecular levelMouse modelRecent studiesAging processTelomeresSenescenceTumorigenesisPathwayMechanismAgingCancerSyndromeEndogenous oncogenic K-rasG12D stimulates proliferation and widespread neoplastic and developmental defects
Tuveson D, Shaw A, Willis N, Silver D, Jackson E, Chang S, Mercer K, Grochow R, Hock H, Crowley D, Hingorani S, Zaks T, King C, Jacobetz M, Wang L, Bronson R, Orkin S, DePinho R, Jacks T. Endogenous oncogenic K-rasG12D stimulates proliferation and widespread neoplastic and developmental defects. Cancer Cell 2004, 5: 375-387. PMID: 15093544, DOI: 10.1016/s1535-6108(04)00085-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell CycleCell DivisionCell Transformation, NeoplasticCellular SenescenceCongenital AbnormalitiesCrosses, GeneticCyclin-Dependent Kinase Inhibitor p16Embryo, MammalianFemaleFibroblastsGene Expression Regulation, DevelopmentalGenes, rasIntegrasesMaleMiceMice, Inbred C57BLMice, TransgenicMutationNeoplasmsStem CellsTumor Suppressor Protein p14ARFTumor Suppressor Protein p53Viral ProteinsConceptsCanonical Ras effectorRas effectorsOncogenic RasEmbryonic developmentAbnormal cellular proliferationDevelopmental defectsRas oncogeneGenetic lesionsConditional expressionWidespread expressionK-RasG12DCellular proliferationFurther genetic abnormalitiesEnhanced proliferationOncogeneProliferationExpressionGenetic abnormalitiesEffectorsMutationsAllelesRegulationPathwayFibroblastsFrank malignancy
2002
Telomerase extracurricular activities
Chang S, DePinho R. Telomerase extracurricular activities. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 12520-12522. PMID: 12271146, PMCID: PMC130491, DOI: 10.1073/pnas.212514699.Peer-Reviewed Original Research
2000
Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation
Wong K, Chang S, Weiler S, Ganesan S, Chaudhuri J, Zhu C, Artandi S, Rudolph K, Gottlieb G, Chin L, Alt F, DePinho R. Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nature Genetics 2000, 26: 85-88. PMID: 10973255, DOI: 10.1038/79232.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell NucleusCell SurvivalChromosome AberrationsChromosomesDNA FragmentationDNA RepairDose-Response Relationship, RadiationFibroblastsGenotypeIn Situ Nick-End LabelingKineticsMiceMice, TransgenicModels, GeneticRadiation ToleranceRadiation, IonizingTelomereThymus GlandTime FactorsConceptsMouse embryonic fibroblastsTelomere functionOrganismal responsesLinear eukaryotic chromosomesDNA repair machineryTelomerase RNA geneNon-homologous endImpairs DNA repairRole of telomeraseTelomerase-deficient miceEukaryotic chromosomesRNA genesYeast telomeresNucleoprotein complexesRepair machineryDNA repairIntact telomeresCrypt stem cellsEmbryonic fibroblastsTelomere dysfunctionDe novo synthesisChromosomal repairGenetic instabilityPrimary thymocytesRate of apoptosisInhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery
Rudolph K, Chang S, Millard M, Schreiber-Agus N, DePinho R. Inhibition of Experimental Liver Cirrhosis in Mice by Telomerase Gene Delivery. Science 2000, 287: 1253-1258. PMID: 10678830, DOI: 10.1126/science.287.5456.1253.Peer-Reviewed Original ResearchConceptsLiver cirrhosisChronic diseasesEnd-stage organ failureChronic liver injuryImproved liver functionExperimental liver cirrhosisLiver injuryOrgan failureLiver functionTelomerase-deficient miceTelomere dysfunctionHigh cellular turnoverTelomerase therapyChemical ablationCirrhosisAdenoviral deliveryLiver regenerationSuch diseasesDiseaseMiceTelomerase activityDysfunctionLiverCellular turnoverShort dysfunctional telomeres