2025
Development and Characterization of an Inducible Bacterial Artificial Chromosome System for Studying Lytic Replication and Pathogenesis of Kaposi's Sarcoma‐Associated Herpesvirus
Xu X, Dong P, Li W, Wang X, Ming Z, Liu Z, Zhu F, Liang Q. Development and Characterization of an Inducible Bacterial Artificial Chromosome System for Studying Lytic Replication and Pathogenesis of Kaposi's Sarcoma‐Associated Herpesvirus. Journal Of Medical Virology 2025, 97: e70392. PMID: 40358030, DOI: 10.1002/jmv.70392.Peer-Reviewed Original ResearchConceptsBacterial artificial chromosomeKSHV lytic replicationLytic replicationViral proteinsCellular genesBAC backboneBacterial artificial chromosome systemContext of virus infectionTargets of viral proteinsFused fluorescent proteinsHygromycin selectable markerPathogenesis of Kaposi's sarcoma-associated herpesvirusKaposi's sarcoma-associated herpesvirusEfficient lytic replicationChromosome systemArtificial chromosomeHerpesvirus genomesSarcoma-associated herpesvirusSubcellular localizationSelectable markerResponse elementGene knockoutFluorescent proteinCRISPR-Cas9Progeny virus
2024
Selenomethionine supplementation mitigates fluoride-induced liver apoptosis and inflammatory reactions by blocking Parkin-mediated mitophagy in mice
Wang T, Li H, Li Y, Li M, Zhao H, Zhang W, Zhao T, Wang Y, Wang J, Wang J. Selenomethionine supplementation mitigates fluoride-induced liver apoptosis and inflammatory reactions by blocking Parkin-mediated mitophagy in mice. The Science Of The Total Environment 2024, 951: 175458. PMID: 39142410, DOI: 10.1016/j.scitotenv.2024.175458.Peer-Reviewed Original ResearchParkin-mediated mitophagyCysteinyl aspartate specific proteinase 3Protein expression levelsLight chain 3Expression levelsInterleukin-6Wild-typeLiver damageContents of proinflammatory factorsTumor necrosis factor-aNuclear factor kappa BLevels of liver functionMitochondrial fusionFactor kappa BParkin-/-Inflammatory signaling pathwaysMicrotubule-associated protein light chain 3MitophagyInterferon-gMitochondrial alterationsProtein light chain 3Gene knockoutIFN-gFluorosis miceLiver function
2023
Lineage-specific genes are clustered with HET-domain genes and respond to environmental and genetic manipulations regulating reproduction in Neurospora
Wang Z, Wang Y, Kasuga T, Lopez-Giraldez F, Zhang Y, Zhang Z, Wang Y, Dong C, Sil A, Trail F, Yarden O, Townsend J. Lineage-specific genes are clustered with HET-domain genes and respond to environmental and genetic manipulations regulating reproduction in Neurospora. PLOS Genetics 2023, 19: e1011019. PMID: 37934795, PMCID: PMC10684091, DOI: 10.1371/journal.pgen.1011019.Peer-Reviewed Original ResearchConceptsLineage-specific genesHET domain genesSexual reproductionFunctional roleUnusual carbon sourcesPotential functional roleMating lociAsexual growthGenetic mutantsNeurospora crassaPossible functional roleSexual phaseGenetic manipulationTranscriptomic profilingReproduction regulationGene knockoutPP-1ADV-1Environmental alterationsGenesSexual developmentNeurosporaReproductionCarbon sourceGenetic barrierSynaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle
Bera M, Radhakrishnan A, Coleman J, Sundaram R, Ramakrishnan S, Pincet F, Rothman J. Synaptophysin chaperones the assembly of 12 SNAREpins under each ready-release vesicle. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2311484120. PMID: 37903271, PMCID: PMC10636311, DOI: 10.1073/pnas.2311484120.Peer-Reviewed Original ResearchConceptsSpecific molecular functionsSynaptic vesicle protein synaptophysinTarget membrane bilayerSensor synaptotagminSNARE proteinsMolecular functionsMembrane proteinsSNAREpinsReceptor vesiclesSingle-molecule measurementsGene knockoutMembrane bilayerLipid bilayersProtein synaptophysinVesiclesDetergent extractsHexamer structureSYPMechanism of actionProteinAssemblyChaperonesSynaptotagminExocytosisBilayers
2022
Systematic identification of biomarker-driven drug combinations to overcome resistance
Rees M, Brenan L, do Carmo M, Duggan P, Bajrami B, Arciprete M, Boghossian A, Vaimberg E, Ferrara S, Lewis T, Rosenberg D, Sangpo T, Roth J, Kaushik V, Piccioni F, Doench J, Root D, Johannessen C. Systematic identification of biomarker-driven drug combinations to overcome resistance. Nature Chemical Biology 2022, 18: 615-624. PMID: 35332332, DOI: 10.1038/s41589-022-00996-7.Peer-Reviewed Original ResearchConceptsSmall molecule responsesCell linesGSK-J4Gene expression featuresMonoacylglycerol lipaseGene knockoutSerine hydrolaseCancer cell linesSystematic identificationCell viability profileInsensitive cell linesNovel relationshipSmall moleculesMechanism of actionEnzymatic modificationSpecific mechanismsViability profileIntrinsic resistanceVariable responseMechanistic studiesRational candidatesMechanismTracing the cis-regulatory changes underlying the endometrial control of placental invasion
Suhail Y, Maziarz JD, Novin A, Dighe A, Afzal J, Wagner G, Kshitiz. Tracing the cis-regulatory changes underlying the endometrial control of placental invasion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2111256119. PMID: 35110402, PMCID: PMC8832988, DOI: 10.1073/pnas.2111256119.Peer-Reviewed Original ResearchConceptsCis-regulatory changesComparative genomic investigationCis-regulatory elementsTranscription factor GATA2Placental invasionCancer cell invasionEutherian mammalsTranscription factorsGenomic investigationsInvasibilityGene knockoutGenomic mechanismsDifferent speciesCell invasionEndometrial controlCancer malignancyDegree of invasionSpecies differencesCancer disseminationMaternal endometriumInterspecies differencesPlacental trophoblastsStromal cellsStromal characteristicsInvasion
2021
Xenopus as a platform for discovery of genes relevant to human disease
Kostiuk V, Khokha MK. Xenopus as a platform for discovery of genes relevant to human disease. Current Topics In Developmental Biology 2021, 145: 277-312. PMID: 34074532, PMCID: PMC8734201, DOI: 10.1016/bs.ctdb.2021.03.005.Peer-Reviewed Original ResearchConceptsCandidate genesHuman diseasesDiscovery of genesScreen candidate genesMultiple candidate genesPatient genomic dataHuman genomePatient phenotypesDisease pathogenesisGenomic dataComplex phenotypesFate mapGene knockoutKnockdown strategyPatient mutationsBirth defectsXenopusFunctional studiesGenesPhenotypeCongenital birthAbnormal developmentCongenital heart diseaseCause of deathBetter diagnostic methods
2019
High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
Abeler-Dörner L, Laing A, Lorenc A, Ushakov D, Clare S, Speak A, Duque-Correa M, White J, Ramirez-Solis R, Saran N, Bull K, Morón B, Iwasaki J, Barton P, Caetano S, Hng K, Cambridge E, Forman S, Crockford T, Griffiths M, Kane L, Harcourt K, Brandt C, Notley G, Babalola K, Warren J, Mason J, Meeniga A, Karp N, Melvin D, Cawthorne E, Weinrick B, Rahim A, Drissler S, Meskas J, Yue A, Lux M, Song-Zhao G, Chan A, Ballesteros Reviriego C, Abeler J, Wilson H, Przemska-Kosicka A, Edmans M, Strevens N, Pasztorek M, Meehan T, Powrie F, Brinkman R, Dougan G, Jacobs W, Lloyd C, Cornall R, Maloy K, Grencis R, Griffiths G, Adams D, Hayday A. High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation. Nature Immunology 2019, 21: 86-100. PMID: 31844327, PMCID: PMC7338221, DOI: 10.1038/s41590-019-0549-0.Peer-Reviewed Original ResearchConceptsHigh-throughput genetic screensImmune variationHigh-throughput phenotypingMouse gene knockoutsAssociated with immunocompetenceGenetic screeningLoss of functionContribution of geneticsPhysiological traitsGenetic resourcesGene knockoutIndividual immune parametersImmune parametersCorrelation networkPhenotypeImmunological structureTolerance to lossGenesHitsGeneticsStructural underpinningsTraitsKnockoutStructural perspectiveVariationBOK promotes erythropoiesis in a mouse model of myelodysplastic syndrome
Kang SH, Perales O, Michaud M, Katz SG. BOK promotes erythropoiesis in a mouse model of myelodysplastic syndrome. Annals Of Hematology 2019, 98: 2089-2096. PMID: 31203423, PMCID: PMC6702064, DOI: 10.1007/s00277-019-03726-7.Peer-Reviewed Original ResearchConceptsUnfolded protein responseER stressPro-apoptotic membersBcl-2 familyNHD13 miceRT-qPCR analysisInduction of apoptosisProgenitor stem cellsHematopoietic progenitor cell assaysProtein responseDownstream effectorsGene knockoutMyelodysplastic syndromeCell stressProgenitor cell assaysEndoplasmic reticulumLower mean cell hemoglobin concentrationErythroid progenitorsNUP98-HOXD13 transgenic miceClonal hematopoietic stem cell disordersStem cellsSimilar overall survivalAcute myeloid leukemiaHematopoietic stem cell disordersMean cell hemoglobin concentrationCombining Rapid Data Independent Acquisition and CRISPR Gene Deletion for Studying Potential Protein Functions: A Case of HMGN1
Mehnert M, Li W, Wu C, Salovska B, Liu Y. Combining Rapid Data Independent Acquisition and CRISPR Gene Deletion for Studying Potential Protein Functions: A Case of HMGN1. Proteomics 2019, 19: e1800438. PMID: 30901150, DOI: 10.1002/pmic.201800438.Peer-Reviewed Original ResearchConceptsChromosomal protein HMG-14DIA-MSDIA mass spectrometryPotential protein functionsCRISPR-Cas gene editingImmune regulation processesCancer cellsExtracellular proteomeChromatin structureHistone inactivationFunctional annotationProtein functionCellular functionsRegulation eventsImportant functional implicationsHMG 14Gene knockoutEnrichment analysisData-independent acquisitionHMGN1Protein deletionCRISPR experimentsGene editingStress pathwaysIndependent acquisition
2017
Lead promotes abnormal angiogenesis induced by CCM3 gene defects via mitochondrial pathway
Sun Y, Zhang H, Xing X, Zhao Z, He J, Li J, Chen J, Wang M, He Y. Lead promotes abnormal angiogenesis induced by CCM3 gene defects via mitochondrial pathway. Journal Of Developmental Origins Of Health And Disease 2017, 9: 182-190. PMID: 29110746, DOI: 10.1017/s2040174417000782.Peer-Reviewed Original ResearchConceptsMouse embryosYolk sacHeterozygous mouse embryosGene defectsCCM3 genesPrimary human umbilical vein endothelial cellsLead exposureMitochondrial DNAEmbryonic developmentMtDNA biogenesisMitochondrial morphologyCardiovascular developmentHuman umbilical vein endothelial cellsMitochondrial pathwayGene knockoutEndothelial cellsUmbilical vein endothelial cellsVascular developmentMitochondria pathwayVein endothelial cellsPrimary cellsGenesRNA expressionCell proliferationEmbryosMechanistic Role of Thioredoxin 2 in Heart Failure
Chen C, Chen H, Zhou HJ, Ji W, Min W. Mechanistic Role of Thioredoxin 2 in Heart Failure. Advances In Experimental Medicine And Biology 2017, 982: 265-276. PMID: 28551792, DOI: 10.1007/978-3-319-55330-6_14.Peer-Reviewed Original ResearchConceptsThioredoxin 2ASK1-dependent apoptosisMechanistic roleMitochondrial reactive oxygen species generationCellular oxidative stressGlobal gene knockoutMitochondrial proteinsEmbryonic lethalityMitochondrial Trx2Gene knockoutKinase 1Reactive oxygen species generationTrx2Key mechanistic roleOxygen species generationCardiomyocyte apoptosisActive tissuesApoptosisCommon mechanismOxidative stressSpecies generationPromising targetHeart failureTherapeutic strategiesTreatment of DCM
2015
An integrated map of structural variation in 2,504 human genomes
Sudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, Zhang Y, Ye K, Jun G, Hsi-Yang Fritz M, Konkel MK, Malhotra A, Stütz AM, Shi X, Paolo Casale F, Chen J, Hormozdiari F, Dayama G, Chen K, Malig M, Chaisson MJP, Walter K, Meiers S, Kashin S, Garrison E, Auton A, Lam HYK, Jasmine Mu X, Alkan C, Antaki D, Bae T, Cerveira E, Chines P, Chong Z, Clarke L, Dal E, Ding L, Emery S, Fan X, Gujral M, Kahveci F, Kidd JM, Kong Y, Lameijer EW, McCarthy S, Flicek P, Gibbs RA, Marth G, Mason CE, Menelaou A, Muzny DM, Nelson BJ, Noor A, Parrish NF, Pendleton M, Quitadamo A, Raeder B, Schadt EE, Romanovitch M, Schlattl A, Sebra R, Shabalin AA, Untergasser A, Walker JA, Wang M, Yu F, Zhang C, Zhang J, Zheng-Bradley X, Zhou W, Zichner T, Sebat J, Batzer MA, McCarroll SA, Mills R, Gerstein M, Bashir A, Stegle O, Devine S, Lee C, Eichler E, Korbel J. An integrated map of structural variation in 2,504 human genomes. Nature 2015, 526: 75-81. PMID: 26432246, PMCID: PMC4617611, DOI: 10.1038/nature15394.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceGenetic Predisposition to DiseaseGenetic VariationGenetics, MedicalGenetics, PopulationGenome-Wide Association StudyGenome, HumanGenomicsGenotypeHaplotypesHomozygoteHumansMolecular Sequence DataMutation RatePhysical Chromosome MappingPolymorphism, Single NucleotideQuantitative Trait LociSequence Analysis, DNASequence DeletionConceptsStructural variantsHuman genomeExpression quantitative trait lociGenome-wide association studiesIndividual mutational eventsQuantitative trait lociComplex structural variantsHomozygous gene knockoutsDNA sequencing dataLoci subjectTrait lociHuman genesGene knockoutIntegrated mapSequencing dataAssociation studiesMutational eventsHaplotype blocksVariant classesFunctional impactPopulation stratificationGenomeNumerous diseasesHuman populationStructural variations
2011
The Action Mechanism of the Myc Inhibitor Termed Omomyc May Give Clues on How to Target Myc for Cancer Therapy
Savino M, Annibali D, Carucci N, Favuzzi E, Cole M, Evan G, Soucek L, Nasi S. The Action Mechanism of the Myc Inhibitor Termed Omomyc May Give Clues on How to Target Myc for Cancer Therapy. PLOS ONE 2011, 6: e22284. PMID: 21811581, PMCID: PMC3141027, DOI: 10.1371/journal.pone.0022284.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCell SurvivalCells, CulturedDown-RegulationEpigenesis, GeneticFibroblastsHumansIntracellular SpaceMiceMolecular Targeted TherapyNeoplasmsPeptide FragmentsPromoter Regions, GeneticProtein BindingProtein TransportProteinsProto-Oncogene Proteins c-mycRatsRepressor ProteinsSerumTranscription, GeneticTranscriptional ActivationUp-RegulationConceptsMiz-1E-boxTargeting MYCProtein interactionsBinding to E-boxesMyc protein interactionsPromoter E-boxTransactivation of target genesBinding to promotersH3 lysine 9MYC interactomeHLH proteinsRepressed genesCancer therapyLysine 9Gene productsRNA interferenceCancer model in vivoOmomycEpigenetic changesTarget genesGene knockoutDecreased acetylationMYCN-myc
2005
Mosaic Analysis with Double Markers in Mice
Zong H, Espinosa JS, Su HH, Muzumdar MD, Luo L. Mosaic Analysis with Double Markers in Mice. Cell 2005, 121: 479-492. PMID: 15882628, DOI: 10.1016/j.cell.2005.02.012.Peer-Reviewed Original ResearchConceptsInterchromosomal recombinationCerebellar granule cell progenitorsGranule cell progenitorsHomologous chromosomesMosaic analysisChimeric geneSomatic cellsAxonal projectionsC-terminusGene knockoutCell lineagesN-terminusPostmitotic cellsGranule cellsCerebellar cortexNeuronal connectionsFunctional expressionCell progenitorsDouble markersConditional knockoutSmall populationSingle cellsSpecific sublayersTerminusMarkers
2004
LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1
Yang X, Yu K, Hao Y, Li DM, Stewart R, Insogna KL, Xu T. LATS1 tumour suppressor affects cytokinesis by inhibiting LIMK1. Nature Cell Biology 2004, 6: 609-617. PMID: 15220930, DOI: 10.1038/ncb1140.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActin Depolymerizing FactorsActomyosinAnimalsAnimals, NewbornAntibodiesCell CycleCell DivisionCells, CulturedDNA-Binding ProteinsFeedback, PhysiologicalFetusGiant CellsHeLa CellsHumansLim KinasesMiceMice, KnockoutMicrofilament ProteinsPhosphorylationPolymersProtein BindingProtein KinasesProtein Serine-Threonine KinasesRNA InterferenceConceptsTumor suppressorActomyosin contractile ringPhosphorylation of cofilinCytokinesis defectsCytoskeleton regulatorsAntibody microinjectionContractile ringActin polymerizationGene knockoutCytokinesisLIMK1LATS1Multinucleate cellsNegative modulationSuppressorDrosophilaCellsColocalizesCofilinMammals
2001
Chromosome Targeting at Short Polypurine Sites by Cationic Triplex-forming Oligonucleotides*
Vasquez K, Dagle J, Weeks D, Glazer P. Chromosome Targeting at Short Polypurine Sites by Cationic Triplex-forming Oligonucleotides*. Journal Of Biological Chemistry 2001, 276: 38536-38541. PMID: 11504712, DOI: 10.1074/jbc.m101797200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCationsChromosomesCOS CellsDiaminesDNADNA Mutational AnalysisDose-Response Relationship, DrugEthylenediaminesFicusinGenes, ReporterGenes, SuppressorGenetic TechniquesGenomeIndicators and ReagentsMagnesiumMiceMice, KnockoutModels, GeneticMolecular Sequence DataMutagenesisMutagenesis, Site-DirectedNucleic Acid ConformationPotassiumProtein BindingPurinesRNA, TransferSequence Homology, Nucleic AcidConceptsChromosomal reporter geneMonkey COS cellsTarget siteSite-specific mutationsTriplex target sitesChromosome targetingEpisomal targetChromosomal targetsGene mutagenesisMammalian cellsSite-specific inductionChromosomal lociReporter geneCOS cellsGene knockoutGenomic DNAMouse cellsSite-directed modificationOligonucleotide bindsPhosphodiester bondShort sitesThird strand bindingPhosphodiester backboneSystemic administrationDNA
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