2025
Dynamic interaction of spliceosomal snRNPs with coilin explains Cajal body characteristics
Basello D, Blažíková M, Roithová A, Hálová M, Radivojević N, Neugebauer K, Staněk D. Dynamic interaction of spliceosomal snRNPs with coilin explains Cajal body characteristics. Journal Of Cell Biology 2025, 224: e202309128. PMID: 40560171, PMCID: PMC12189012, DOI: 10.1083/jcb.202309128.Peer-Reviewed Original Research
2024
Cell Growth Trajectories of B-Cell Lymphomas Are Defined By Oscillations between MYC- and BCL6-Dependent States
Cheng Z, Kume K, Shanmugam V, Müschen M. Cell Growth Trajectories of B-Cell Lymphomas Are Defined By Oscillations between MYC- and BCL6-Dependent States. Blood 2024, 144: 45-45. DOI: 10.1182/blood-2024-206563.Peer-Reviewed Original ResearchActivation of MYCCell divisionCell growthDNA damage-induced apoptosisTurnover of damaged organellesB-cell lymphomaTranscriptional activity of MYCChIP-seq dataDamage-induced apoptosisOscillatory expression patternsCell shrinkageDegradation of MycPhenotype to cellsTranscription of MYCInduce transcriptional activationAmino acid depletionTime-lapse confocal imagingLive-cell imagingStall cell growthB cell developmentChIP-seqB cellsDegron systemRepress transcriptionCell sizeThe condensation of HP1α/Swi6 imparts nuclear stiffness
Williams J, Surovtsev I, Schreiner S, Chen Z, Raiymbek G, Nguyen H, Hu Y, Biteen J, Mochrie S, Ragunathan K, King M. The condensation of HP1α/Swi6 imparts nuclear stiffness. Cell Reports 2024, 43: 114373. PMID: 38900638, PMCID: PMC11348953, DOI: 10.1016/j.celrep.2024.114373.Peer-Reviewed Original ResearchSingle-molecule imagingBiomolecular condensatesSeparation-of-function alleleHeterochromatin protein HP1aChromatin-bound moleculesHigh-resolution live-cell imagingLive-cell imagingCondensationHeterochromatin domainsMethylated nucleosomesSwi6Nuclear stiffnessForce spectroscopyChromatin meshworkCellular organizationCell mechanicsDynamic pool
2023
Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity
Higerd-Rusli G, Tyagi S, Baker C, Liu S, Dib-Hajj F, Dib-Hajj S, Waxman S. Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2215417120. PMID: 36897973, PMCID: PMC10089179, DOI: 10.1073/pnas.2215417120.Peer-Reviewed Original ResearchConceptsCell biological mechanismsAxonal surfaceLive-cell imagingIon channel traffickingAnterograde transport vesiclesTransport vesiclesInflammatory mediatorsChannel traffickingPlasma membraneVesicular loadingIon channelsKv channelsPotential therapeutic targetPotassium channel KSodium channel NaTraffickingBiological mechanismsTherapeutic targetAbundanceRetrograde transportDistal axonsChannel NaInflammatory painNociceptor activityAxonal transport
2022
Regulation of EGF-stimulated activation of the PI-3K/AKT pathway by exocyst-mediated exocytosis
An S, Anneken A, Xi Z, Choi C, Schlessinger J, Toomre D. Regulation of EGF-stimulated activation of the PI-3K/AKT pathway by exocyst-mediated exocytosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2208947119. PMID: 36417441, PMCID: PMC9860279, DOI: 10.1073/pnas.2208947119.Peer-Reviewed Original ResearchConceptsPI-3K/Akt pathwayAkt pathwayAkt activationDocking protein Gab1EGF-stimulated activationEpithelial cellsLive-cell imagingPhosphoinositide-3 kinaseCell survival pathwaysExocyst complexExocyst functionSmall molecule inhibitorsVesicle tethersExocytic fusionProtein Gab1EGF stimulationExocystSurvival pathwaysExocytosisInhibitors resultsPathwayImportant pathwayEGFR inhibitionMinute time scaleVesiclesSystematic generation and imaging of tandem repeats reveal base-pairing properties that promote RNA aggregation
Isiktas A, Eshov A, Yang S, Guo J. Systematic generation and imaging of tandem repeats reveal base-pairing properties that promote RNA aggregation. Cell Reports Methods 2022, 2: 100334. PMID: 36452875, PMCID: PMC9701603, DOI: 10.1016/j.crmeth.2022.100334.Peer-Reviewed Original ResearchConceptsBase pairsRNA aggregationRNA-RNA interactionsLive-cell imagingConsecutive base pairsNoncanonical base pairsRNA aggregatesRepeat RNARepeat DNAMolecular basisRepeat sequencesMolecular mechanismsTandem repeatsRNAHexanucleotide repeatsStructural determinantsGGGGCC hexanucleotide repeatBase-pairing propertiesCommon pathological featureRepeatsSequenceUnifying modelGeneralizable approachDistinct propertiesEnhanced aggregationOligodendroglial macroautophagy is essential for myelin sheath turnover to prevent neurodegeneration and death
Aber ER, Griffey CJ, Davies T, Li AM, Yang YJ, Croce KR, Goldman JE, Grutzendler J, Canman JC, Yamamoto A. Oligodendroglial macroautophagy is essential for myelin sheath turnover to prevent neurodegeneration and death. Cell Reports 2022, 41: 111480. PMID: 36261002, PMCID: PMC9639605, DOI: 10.1016/j.celrep.2022.111480.Peer-Reviewed Original ResearchConceptsCell typesLive-cell imagingNeurodegenerative disease pathophysiologySuch cell typesMouse geneticsAdult-onset neurodegenerative diseaseMacroautophagyCell imagingNeurodegenerative diseasesMyelin proteinsNeurodegenerationDisease pathophysiologyTurnoverMature oligodendrocytesCentral nervous systemAmphisomesMyelin sheath structureNeural functionNervous systemMyelin turnoverGeneticsMyelin sheathProgressive motor declineProteinHomeostasisLive-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer
Yi E, Gujar A, Guthrie M, Kim H, Zhao D, Johnson K, Amin S, Costa M, Yu Q, Das S, Jillette N, Clow P, Cheng A, Verhaak R. Live-Cell Imaging Shows Uneven Segregation of Extrachromosomal DNA Elements and Transcriptionally Active Extrachromosomal DNA Hubs in Cancer. Cancer Discovery 2022, 12: 468-483. PMID: 34819316, PMCID: PMC8831456, DOI: 10.1158/2159-8290.cd-21-1376.Peer-Reviewed Original ResearchConceptsExtrachromosomal DNA elementsDNA elementsUneven segregationRNA polymerase IILive-cell imagingPolymerase IIOffspring cellsGene transcriptionCell line modelsEcDNAsRandom segregationGenetic materialLiving cellsCopy numberLive cellsIndividual cellsTumor evolutionMitosisInheritance patternBreakpoint sequencesIssue featureTranscriptionFluorescent markersPatient tissuesCells
2020
Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding
Kadry YA, Maisuria EM, Huet-Calderwood C, Calderwood DA. Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding. Journal Of Biological Chemistry 2020, 295: 11161-11173. PMID: 32546480, PMCID: PMC7415974, DOI: 10.1074/jbc.ra120.013618.Peer-Reviewed Original ResearchConceptsKindlin-3Kindlin-2Focal adhesionsIntegrin cytoplasmic domainTransmembrane adhesion receptorsComparative sequence analysisLive-cell imagingAbility of cellsCytoplasmic domainF3 subdomainsMammalian cellsCytoplasmic componentsExtracellular environmentAdhesion receptorsKindlinSequence analysisIntegrin familySelf-associationIntegrin bindingPhysiological importanceMolecular levelPoint mutationsProteinCellsAdhesionApplying Live Cell Imaging and Cryo-Electron Tomography to Resolve Spatiotemporal Features of the Legionella pneumophila Dot/Icm Secretion System.
Chetrit D, Park D, Hu B, Liu J, Roy CR. Applying Live Cell Imaging and Cryo-Electron Tomography to Resolve Spatiotemporal Features of the Legionella pneumophila Dot/Icm Secretion System. Journal Of Visualized Experiments 2020 PMID: 32225141, DOI: 10.3791/60693.Peer-Reviewed Original ResearchConceptsDot/Icm secretion systemCryo-electron tomographySecretion systemCryo-ETDot/Icm systemDot/Icm apparatusDot/IcmSuperfolder green fluorescent proteinLive-cell imagingGreen fluorescent proteinIntact bacterial cellsPolar positioningSecretion complexPolar localizationQuantitative fluorescence microscopyBacterial poleATPase geneCytoplasmic complexDelivery of proteinsDNA substratesTiming of productionIcm systemFluorescent proteinLiving cellsBacterial cells
2019
Microfluidic platform enables live-cell imaging of signaling and transcription combined with multiplexed secretion measurements in the same single cells
Ramji R, Alexander AF, Muñoz-Rojas AR, Kellman LN, Miller-Jensen K. Microfluidic platform enables live-cell imaging of signaling and transcription combined with multiplexed secretion measurements in the same single cells. Integrative Biology 2019, 11: 142-153. PMID: 31242304, PMCID: PMC8672722, DOI: 10.1093/intbio/zyz013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesCell CommunicationChemokine CCL2Chemokine CCL3Chemokine CCL5Equipment DesignLab-On-A-Chip DevicesLipopolysaccharidesMacrophagesMiceMice, Inbred C57BLMicrofluidicsRAW 264.7 CellsSignal TransductionTranscription Factor RelATranscription, GeneticTumor Necrosis Factor-alphaConceptsLive-cell imagingCell variabilitySame single cellSingle-cell assaysTranscription dynamicsBacterial component lipopolysaccharideDownstream responsesPathogenic assaultFluorescent reportersProtein secretionSingle cellsCell processesBiological sourcesCCL3 secretionRelative levelsCellsInnate immune cellsTranslocation dynamicsBiological stepC secretionTranscriptionSecretionCCL5 secretionRelAReporterA Highly Sensitive Two‐Photon Ratiometric Probe for Rapid Detection of the hNQO1 Enzyme in Colon Cancer Tissue
Cho M, Juvekar V, Lim C, Noh C, Shin S, Kim H. A Highly Sensitive Two‐Photon Ratiometric Probe for Rapid Detection of the hNQO1 Enzyme in Colon Cancer Tissue. Asian Journal Of Organic Chemistry 2019, 8: 1707-1712. DOI: 10.1002/ajoc.201800694.Peer-Reviewed Original ResearchN-methylated amide groupsTwo-photon sensorTwo-photon fluorescent probeN-dimethylamino)naphthaleneAmide groupsTrimethyl-locked quinoneRatiometric probeQuinones to hydroquinonesRedox cyclingFluorescent probeLive-cell imagingSelf-cleavable linkerHT-29 cellsNear-Infrared LightExcitation sourceColon cancer tissuesActivity studiesFast responseHNQO1Human tumor cellsLiving cellsNADH reductionHT-29Human colon tissueCell linesMethodologies to monitor protein turnover at the inner nuclear membrane
Tsai PL, Zhao C, Schlieker C. Methodologies to monitor protein turnover at the inner nuclear membrane. Methods In Enzymology 2019, 619: 47-69. PMID: 30910029, PMCID: PMC6457266, DOI: 10.1016/bs.mie.2018.12.033.Peer-Reviewed Original ResearchConceptsLamin B receptorNuclear envelopeInner nuclear membrane proteinProtein turnoverProtein quality control pathwaysNuclear membrane proteinsQuality control pathwaysProtein turnover machineryHuman congenital disordersInner nuclear membraneSubcellular fractionation methodMammalian nuclear envelopeLive-cell imagingC-terminal truncationsNuclear laminaMembrane proteinsModel substrateBiochemical approachesNuclear compartmentActivity essentialControl pathwaysNuclear membraneRapid turnoverCholesterol biosynthesisCell imagingFold-Change Detection of NF-κB at Target Genes with Different Transcript Outputs
Wong VC, Mathew S, Ramji R, Gaudet S, Miller-Jensen K. Fold-Change Detection of NF-κB at Target Genes with Different Transcript Outputs. Biophysical Journal 2019, 116: 709-724. PMID: 30704857, PMCID: PMC6382958, DOI: 10.1016/j.bpj.2019.01.011.Peer-Reviewed Original ResearchConceptsFold-change detectionTarget genesTranscript outputStress-responsive gene transcriptionSingle-cell dataNF-κB target genesRelA nuclear translocationLive-cell imagingMicrofluidic cell-trapping deviceLow-abundance transcriptsTranscription factor nuclear factorNF-κBRNA FISHTranscriptional outputΚB motifTranscript abundanceGene transcriptionTranscriptionTranscript numbersCell trap deviceJurkat TCell typesGenesNF-κB signalingMultiple biological mechanisms
2018
Role of the mechanosensitive ion channel Piezo1 in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Chebib F, Beyder A, Wang X, Alcaino C, Ehrlich B, Torres V. Role of the mechanosensitive ion channel Piezo1 in Autosomal Dominant Polycystic Kidney Disease (ADPKD). The FASEB Journal 2018, 32: 868.2-868.2. DOI: 10.1096/fasebj.2018.32.1_supplement.868.2.Peer-Reviewed Original ResearchAutosomal dominant polycystic kidney diseaseCalcium entryCyclic AMPMIMCD3 cellsCytoplasmic calciumFluid shear stressWild-type miceDominant polycystic kidney diseaseRenal cystogenesisFull-text articlesNon-selective cation channelsPolycystic kidney diseaseKidney diseaseExperimental Biology 2018 MeetingIntracellular calciumType miceVivo effectsPathogenic mechanismsCystic epitheliumLive-cell imagingMechanosensitive ion channelsSecretory phenotypeATP releaseMechanosensitive ion channel Piezo1Cation channelsPRRT2 Regulates Synaptic Fusion by Directly Modulating SNARE Complex Assembly
Coleman J, Jouannot O, Ramakrishnan SK, Zanetti MN, Wang J, Salpietro V, Houlden H, Rothman JE, Krishnakumar SS. PRRT2 Regulates Synaptic Fusion by Directly Modulating SNARE Complex Assembly. Cell Reports 2018, 22: 820-831. PMID: 29346777, PMCID: PMC5792450, DOI: 10.1016/j.celrep.2017.12.056.Peer-Reviewed Original ResearchConceptsProline-rich transmembrane protein 2SNARE complex assemblyComplex assemblyTrans-SNARE complex assemblyTerminal proline-rich domainSynaptic SNARE proteinsProline-rich domainParoxysmal neurological disordersSynaptic vesicle primingLive-cell imagingTransmembrane protein 2Synaptic fusionSNARE proteinsVesicle primingSingle exocytotic eventsBiophysical analysisFusion assaysMolecular mechanismsFunction mutationsPhysiological roleExocytotic eventsPre-synaptic terminalsPC12 cellsProtein 2Single vesiclesNF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional Noise
Wong VC, Bass VL, Bullock ME, Chavali AK, Lee REC, Mothes W, Gaudet S, Miller-Jensen K. NF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional Noise. Cell Reports 2018, 22: 585-599. PMID: 29346759, PMCID: PMC5812697, DOI: 10.1016/j.celrep.2017.12.080.Peer-Reviewed Original ResearchConceptsTranscriptional noiseIntegration sitesDiverse phenotypesRNA polymerase II regulationNoisy gene expressionGenomic integration sitesLive-cell imagingNF-κB activationChromatin environmentChromatin stateViral activationChromatin interactionsTranscript abundanceTranscription factor nuclear factor κBDivergent phenotypesGene expressionNoisy expressionNF-κBTranscript numbersNuclear factor κBPhenotypeTumor necrosis factorFactor κBActivationExpression
2017
Adding dimension to cellular mechanotransduction: Advances in biomedical engineering of multiaxial cell-stretch systems and their application to cardiovascular biomechanics and mechano-signaling
Friedrich O, Schneidereit D, Nikolaev Y, Nikolova-Krstevski V, Schürmann S, Wirth-Hücking A, Merten A, Fatkin D, Martinac B. Adding dimension to cellular mechanotransduction: Advances in biomedical engineering of multiaxial cell-stretch systems and their application to cardiovascular biomechanics and mechano-signaling. Progress In Biophysics And Molecular Biology 2017, 130: 170-191. PMID: 28647645, DOI: 10.1016/j.pbiomolbio.2017.06.011.Peer-Reviewed Original ResearchConceptsFocal adhesion complexesCell-substrate junctionLive-cell imagingMechanosensitive ion channelsDirect mechanistic studiesAdhesion complexesCellular mechanotransductionMembrane junctionsIntracellular signalingMechanotransduction researchCellular stretchCellular modelIon channelsCellular levelCell membraneMechanotransductionIndividual cardiomyocytesBiomedical engineeringMechanical wall stressMembraneMechanistic studiesCellsStretch deviceCardiomyocytesElastomeric membrane
2016
Sphingomyelin is sorted at the trans Golgi network into a distinct class of secretory vesicle
Deng Y, Rivera-Molina FE, Toomre DK, Burd CG. Sphingomyelin is sorted at the trans Golgi network into a distinct class of secretory vesicle. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 6677-6682. PMID: 27247384, PMCID: PMC4914164, DOI: 10.1073/pnas.1602875113.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkSynthesis of sphingomyelinGolgi networkSecretory vesiclesPlasma membraneQuantitative live-cell imagingVesicular transport carriersSorting of proteinsGlycophosphatidylinositol-anchored proteinsPore-forming toxinsLive-cell imagingInterorganelle traffickingAbundant sphingolipidIntracellular traffickingSecretory proteinsSM transportTransport carriersProteinCell imagingTraffickingDistinct classesSpecific carrierVesiclesPrincipal functionSorting
2015
Epigenetic predisposition to reprogramming fates in somatic cells
Pour M, Pilzer I, Rosner R, Smith ZD, Meissner A, Nachman I. Epigenetic predisposition to reprogramming fates in somatic cells. EMBO Reports 2015, 16: 370-378. PMID: 25600117, PMCID: PMC4364876, DOI: 10.15252/embr.201439264.Peer-Reviewed Original ResearchConceptsSomatic cellsFactor inductionLive-cell imagingPluripotent stem cellsEpigenetic stateCell identitySuccessful reprogrammingEpigenetic heterogeneityDaughter cellsSister cellsCell lineagesCellular responsesLineagesEZH2 inhibitorsLow-efficiency processColony formationStem cellsEpigenetic predispositionReprogramPopulation levelCellsNovel statistical approachSomatic populationInductionFate
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