Featured Publications
Size-dependent activation of CAR-T cells
Xiao Q, Zhang X, Tu L, Cao J, Hinrichs CS, Su X. Size-dependent activation of CAR-T cells. Science Immunology 2022, 7: eabl3995. PMID: 35930653, PMCID: PMC9678385, DOI: 10.1126/sciimmunol.abl3995.Peer-Reviewed Original ResearchConceptsIntermembrane spacePlasma membraneIntracellular domainExtracellular domainMolecular mechanismsLarge isoformDownstream pathwaysT cell activationVariety of cancersCaR's extracellular domainAntigen engagementAntigen receptorSize differencesCell activationActivation of CARActivationMouse lymphoma modelCD45Antigen signalCellsLymphoma modelKinasePhosphorylationCD45RABCViral infectionPLCγ1 promotes phase separation of T cell signaling components
Zeng L, Palaia I, Šarić A, Su X. PLCγ1 promotes phase separation of T cell signaling components. Journal Of Cell Biology 2021, 220: e202009154. PMID: 33929486, PMCID: PMC8094118, DOI: 10.1083/jcb.202009154.Peer-Reviewed Original ResearchConceptsTCR signal transductionT-cell receptor pathwayLiquid-like condensatesKey adaptor proteinLAT clusteringLAT complexSH2 domainAdaptor proteinPhosphatase CD45Signal transductionTCR pathwayPhospholipase Cγ1ERK activationProtein compositionBiophysical principlesPLCγ1Critical functionsReceptor pathwayPathwayLATMajor componentT cellsCellsActivationDephosphorylationRewired signaling network in T cells expressing the chimeric antigen receptor (CAR)
Dong R, Libby KA, Blaeschke F, Fuchs W, Marson A, Vale RD, Su X. Rewired signaling network in T cells expressing the chimeric antigen receptor (CAR). The EMBO Journal 2020, 39: embj2020104730. PMID: 32643825, PMCID: PMC7429742, DOI: 10.15252/embj.2020104730.Peer-Reviewed Original ResearchConceptsCentral supramolecular activation clusterEssential scaffold proteinT cell receptorSupramolecular activation clusterImmunological synapse formationAntigen receptorActin remodelingScaffold proteinMicrocluster formationDownstream signalingTCR signalingT cell activationSynapse formationCancer cellsSpecific cancer cellsCell receptorSignalingCAR activationT cellsCell activationCellsCAR-T cell activationNative T cellsPathwayActivation clusters
2022
SILAC Phosphoproteomics Reveals Unique Signaling Circuits in CAR‑T Cells and the Inhibition of B Cell-Activating Phosphorylation in Target Cells
Griffith AA, Callahan KP, King NG, Xiao Q, Su X, Salomon AR. SILAC Phosphoproteomics Reveals Unique Signaling Circuits in CAR‑T Cells and the Inhibition of B Cell-Activating Phosphorylation in Target Cells. Journal Of Proteome Research 2022, 21: 395-409. PMID: 35014847, PMCID: PMC8830406, DOI: 10.1021/acs.jproteome.1c00735.Peer-Reviewed Original ResearchConceptsCD19 CAR T cellsChimeric antigen receptorRaji B cellsT cellsB cellsCAR T cell activityT cell activityB-cell malignanciesT cell receptor signalingCAR T cell signalingCell receptor signalingCD19-CARCell malignanciesT cell signalingCell activityReceptor signalingAntigen receptorLiquid chromatography-tandem mass spectrometryTarget cellsSignificant decreaseChromatography-tandem mass spectrometryTCR signalingReceptorsResponse of cellsCells
2020
Surfing on Membrane Waves: Microvilli, Curved Membranes, and Immune Signaling
Orbach R, Su X. Surfing on Membrane Waves: Microvilli, Curved Membranes, and Immune Signaling. Frontiers In Immunology 2020, 11: 2187. PMID: 33013920, PMCID: PMC7516127, DOI: 10.3389/fimmu.2020.02187.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsCarrier ProteinsCell LineCell MembraneCell ShapeCyclodextrinsCytokinesGlycocalyxHumansLymphocyte ActivationMembrane LipidsMembrane ProteinsMiceMicrofilament ProteinsMicroscopy, Electron, ScanningMicrovilliReceptors, Antigen, T-CellSignal TransductionStress, MechanicalSurface PropertiesSynaptosomesT-LymphocytesConceptsFunctional consequencesFinger-like membrane protrusionsT cell signalingSuper-resolution microscopyLocal membrane curvatureActin cytoskeletonMembrane protrusionsSignal transductionCell signalingMembrane curvatureCurved membranesImmune signalingBiochemical activityUnique compartmentLymphocyte microvilliMicrovillus formationCell typesLocal membraneCytoskeletonSignalingMicrovilliMembraneBody of evidenceMembrane wavesImportant roleImaging Chimeric Antigen Receptor (CAR) Activation
Libby KA, Su X. Imaging Chimeric Antigen Receptor (CAR) Activation. Methods In Molecular Biology 2020, 2111: 153-160. PMID: 31933206, DOI: 10.1007/978-1-0716-0266-9_13.Peer-Reviewed Original Research
2019
A composition-dependent molecular clutch between T cell signaling condensates and actin
Ditlev JA, Vega AR, Köster DV, Su X, Tani T, Lakoduk AM, Vale RD, Mayor S, Jaqaman K, Rosen MK. A composition-dependent molecular clutch between T cell signaling condensates and actin. ELife 2019, 8: e42695. PMID: 31268421, PMCID: PMC6624021, DOI: 10.7554/elife.42695.Peer-Reviewed Original Research
2016
Phase separation of signaling molecules promotes T cell receptor signal transduction
Su X, Ditlev JA, Hui E, Xing W, Banjade S, Okrut J, King DS, Taunton J, Rosen MK, Vale RD. Phase separation of signaling molecules promotes T cell receptor signal transduction. Science 2016, 352: 595-599. PMID: 27056844, PMCID: PMC4892427, DOI: 10.1126/science.aad9964.Peer-Reviewed Original ResearchConceptsT cell receptor (TCR) signal transductionHuman Jurkat T cellsActin filament assemblySubmicrometer-sized clustersReceptor signal transductionT cell receptor activationProtein phase separationJurkat T cellsCell receptor activationCell surface receptorsTCR phosphorylationActin regulatorsActin assemblySignal transductionFilament assemblyBiochemical compartmentsFunctional consequencesSurface receptorsModel membranesReceptor activationAssemblyActivationTransductionKinasePhosphorylation