Featured Publications
Control of cell state transitions
Rukhlenko O, Halasz M, Rauch N, Zhernovkov V, Prince T, Wynne K, Maher S, Kashdan E, MacLeod K, Carragher N, Kolch W, Kholodenko B. Control of cell state transitions. Nature 2022, 609: 975-985. PMID: 36104561, PMCID: PMC9644236, DOI: 10.1038/s41586-022-05194-y.Peer-Reviewed Original ResearchConceptsCell state transitionsCell fateCell statesCell fate transitionsCell fate decisionsSingle-cell dataNew biological insightsFate transitionsMovement of cellsFate decisionsWaddington landscapePhenotypic dataBiological insightsOmics datasetsOmics dataCellular modelMechanistic modelLandscape1FateCellsDevelopment pathwaysLandscapeBiologyState transitionsTherapeutic interventions
2015
Signalling mechanisms regulating phenotypic changes in breast cancer cells
Volinsky N, McCarthy CJ, von Kriegsheim A, Saban N, Okada-Hatakeyama M, Kolch W, Kholodenko BN. Signalling mechanisms regulating phenotypic changes in breast cancer cells. Bioscience Reports 2015, 35: e00178. PMID: 25643809, PMCID: PMC4370098, DOI: 10.1042/bsr20140172.Peer-Reviewed Original ResearchConceptsCell fate decisionsATP-citrate lyaseFate decisionsPhenotypic changesBreast cancer cellsEpidermal growth factorCell fate decision processesCancer cellsLipid accumulationIrreversible phenotypic changesPhosphoinositide-3 kinaseSimilar cellular responsesPI3K pathwayGrowth factorRapamycin complexKinase pathwayNegative regulatorMolecular mechanismsCellular responsesMetabolic pathwaysMammalian targetK pathwayCitrate lyaseLipogenic pathwayCell proliferation
2013
Complexity of Receptor Tyrosine Kinase Signal Processing
Volinsky N, Kholodenko BN. Complexity of Receptor Tyrosine Kinase Signal Processing. Cold Spring Harbor Perspectives In Biology 2013, 5: a009043. PMID: 23906711, PMCID: PMC3721286, DOI: 10.1101/cshperspect.a009043.Peer-Reviewed Original ResearchConceptsCombinatorial varietySignal processingMathematical modelingSpecific system propertiesSpecific cell fate decisionsSystem propertiesNetwork behaviorReceptor tyrosine kinasesMultiple feedsSpatiotemporal dynamicsComputational approachExcitable responseIntricate landscapeCell fate decisionsSpecific cellular outcomesPathway cross talkOscillationsBistabilityNetwork circuitryDynamicsModelingTranscriptional controlAdapts cellsCellular outcomesPseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2
Reiterer V, Fey D, Kolch W, Kholodenko BN, Farhan H. Pseudophosphatase STYX modulates cell-fate decisions and cell migration by spatiotemporal regulation of ERK1/2. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: e2934-e2943. PMID: 23847209, PMCID: PMC3732994, DOI: 10.1073/pnas.1301985110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell DifferentiationCell MovementCell NucleusDual-Specificity PhosphatasesEnzyme ActivationGene Knockdown TechniquesGolgi ApparatusHumansIntracellular Signaling Peptides and ProteinsMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinase PhosphatasesNuclear ProteinsPC12 CellsRatsConceptsPC12 cell differentiationCell migrationCell differentiationDual-specificity phosphatase familyCell fate decisionsDirectional cell migrationNuclear anchorPhosphatase familySpatiotemporal regulationGolgi polarizationSpatial regulatorCellular signalingNuclear exportERK activityGolgi apparatusERK signalingERK1/2 activationImportant regulatorInactive membersSignalingRegulatorERK1/2StyxDifferentiationDUSPs
2012
Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise
Birtwistle MR, Rauch J, Kiyatkin A, Aksamitiene E, Dobrzyński M, Hoek JB, Kolch W, Ogunnaike BA, Kholodenko BN. Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise. BMC Systems Biology 2012, 6: 109. PMID: 22920937, PMCID: PMC3484110, DOI: 10.1186/1752-0509-6-109.Peer-Reviewed Original ResearchConceptsProtein expression noiseSingle-cell signalingExtracellular signal-regulated kinaseExpression noiseCell variabilityEpidermal growth factor stimulationProtein abundance variationCell fate decisionsPopulation responsesGrowth factor stimulationSingle cellsSignal-regulated kinaseCell population levelProtein expressionSingle-cell levelERK pathway activationFate decisionsPopulation levelFactor stimulationCell signalingCell population responseERK responseBiological outcomesPathway activationCell level