2023
Separation of B- and T-Cell-Specific Signaling Molecules Prevents Oncogenic Transformation in Lymphoid Malignancies
Ketzer F, Klemm L, Robinson M, Loucks C, Arce D, Cosgun K, Kothari S, Müschen M. Separation of B- and T-Cell-Specific Signaling Molecules Prevents Oncogenic Transformation in Lymphoid Malignancies. Blood 2023, 142: 1396. DOI: 10.1182/blood-2023-189221.Peer-Reviewed Original ResearchKinase ZAP70Transcriptional regulationTranscription factorsKinase SykDownstream activationT-cell signaling proteinsCRISPR/Cas9-mediated knockoutComparative proteomic analysisNegative selectionFunction of proteinsWild-type cellsCas9-mediated knockoutCo-expressed proteinsPre-malignant cellsT cell linesCellular fitnessTranscription machinerySLP-76Signaling proteinsMalignant transformationSignal transductionAberrant transcriptionProteomic analysisChIP-qPCRNovel key mechanism
2018
Divergent Evolutionary Trajectories of Erk- and Stat5-Activating Lesions in Acute Lymphoblastic Leukemia
Chan L, Shojaee S, Hurtz C, Auer F, Chen Z, Cosgun K, Geng H, Sadras T, White D, Muschen M. Divergent Evolutionary Trajectories of Erk- and Stat5-Activating Lesions in Acute Lymphoblastic Leukemia. Blood 2018, 132: 568. DOI: 10.1182/blood-2018-99-115536.Peer-Reviewed Original ResearchEvolutionary trajectoriesColony formation abilityCompetitive fitnessCommitment stepPre-B cell receptorDivergent evolutionary trajectoriesUpstream kinase MEKNormal B cell developmentOncogenic signal transductionInducible ablationActivation of STAT5B cell developmentEmpty vector controlActivation of ERKCentral oncogenic driverB-cell transformationImmature B cellsSignal transductionFormation abilityKinase MEKPhosphorylation of ERKGrowth factor receptorPatient-derived preAlternative pathwayERK activityCooperation between SYK and ZAP70 Kinases As a Driver of Oncogenic BCR-Signaling in B-Cell Malignancies
Sadras T, Cutler J, Aguade-Gorgorio J, Chen Z, Cosgun K, Pandey A, Muschen M. Cooperation between SYK and ZAP70 Kinases As a Driver of Oncogenic BCR-Signaling in B-Cell Malignancies. Blood 2018, 132: 3922. DOI: 10.1182/blood-2018-99-116954.Peer-Reviewed Original ResearchSpleen tyrosine kinaseSH2 domainZAP70 kinaseKinase domainCarboxy-terminal kinase domainLinker regionT cell receptorSurvival signalsBCR signalingTyrosine kinaseChronic lymphocytic leukemiaTandem SH2 domainsProximal signal transductionAmino acid insertB-cell malignanciesBCR-mediated signalsB cellsAlternative splice variantsNegative B cell selectionDifferential interactomeProteomic approachInterdomain BZAP70 proteinBCR componentsSignal transduction