2023
Mechanistic Elucidation of the Tumor-Promoting Role of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in B-Cell Receptor Signaling in Mantle Cell Lymphoma
Xavier S, Nguyen V, Khairnar V, Phan A, Yang L, Nelson M, Tseng E, Li A, Song J, Weisenburger D, Chan W, Müschen M, Ngo V. Mechanistic Elucidation of the Tumor-Promoting Role of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in B-Cell Receptor Signaling in Mantle Cell Lymphoma. Blood 2023, 142: 720. DOI: 10.1182/blood-2023-175064.Peer-Reviewed Original ResearchMantle cell lymphomaCell adhesion molecule-1Adhesion molecule-1Proximity ligation assayMCL linesN-terminal domainLipid raft formationSHP-1BCR activationCell lymphomaMolecule-1B cellsCell linesCarcinoembryonic antigen-related cell adhesion molecule 1F-actinRaft formationTerminal ligand-binding domainPhosphorylation levelsGenome-wide screenB-cell receptor signalingRecruitment of SykImmunoreceptor tyrosine-based inhibitory motifPathogenesis of MCLTyrosine-based inhibitory motifCell receptor signalingAn intrinsic purine metabolite AICAR blocks lung tumour growth by targeting oncoprotein mucin 1
Aftab F, Rodriguez-Fuguet A, Silva L, Kobayashi I, Sun J, Politi K, Levantini E, Zhang W, Kobayashi S, Zhang W. An intrinsic purine metabolite AICAR blocks lung tumour growth by targeting oncoprotein mucin 1. British Journal Of Cancer 2023, 128: 1647-1664. PMID: 36810913, PMCID: PMC10133251, DOI: 10.1038/s41416-023-02196-z.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsProximity ligation assayWhole transcriptomic profileEGFR inhibitorsMUC1-CTThermal stability assaysRNA sequencingTransgenic micePurine biosynthesisTranscriptomic profilesAICARTumor cell growthLigation assayMucin 1DNA damageCell growthMethodsCell viabilityLung tumor tissuesTumor formationCancer cellsEGFR-mutant lung cancerStability assaysJAKJAK1Dual immunofluorescence staining
2022
Restricting α-synuclein transport into mitochondria by inhibition of α-synuclein–VDAC complexation as a potential therapeutic target for Parkinson’s disease treatment
Rajendran M, Queralt-Martín M, Gurnev P, Rosencrans W, Rovini A, Jacobs D, Abrantes K, Hoogerheide D, Bezrukov S, Rostovtseva T. Restricting α-synuclein transport into mitochondria by inhibition of α-synuclein–VDAC complexation as a potential therapeutic target for Parkinson’s disease treatment. Cellular And Molecular Life Sciences 2022, 79: 368. PMID: 35718804, PMCID: PMC11072225, DOI: 10.1007/s00018-022-04389-w.Peer-Reviewed Original ResearchConceptsVoltage-dependent anion channelVDAC poreProtein-membrane bindingRegulating mitochondrial functionProximity ligation assayInvolvement of alpha-synucleinMembrane bindingMitochondrial respirationMitochondrial functionHeLa cellsLigation assayLipid membranesHexokinase 2MitochondriaTranslocation processComplex inhibitionAnion channelFluorescence correlation spectroscopyAlpha-synucleinMolecular levelMitochondrial toxicityASynTranslocationPeptide therapeuticsTherapeutic targetCo-Expression and Functional Interactions of Death Receptor 3 and E-Selectin in Clear Cell Renal Cell Carcinoma
Al-Lamki RS, Wang J, Pober JS, Bradley JR. Co-Expression and Functional Interactions of Death Receptor 3 and E-Selectin in Clear Cell Renal Cell Carcinoma. American Journal Of Pathology 2022, 192: 722-736. PMID: 35063404, DOI: 10.1016/j.ajpath.2021.12.010.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseCell cycle entryCcRCC cellsDeath receptor 3Protein kinaseClear cell renal cell carcinoma cellsProximity ligation assayRenal cell carcinoma cellsReceptor 3E-selectinPotential new targetsCycle entryNF-κB-dependent mannerNF-κBLigation assayTumor gradeCcRCC tissuesFunctional interactionSelectin expressionFunctional roleClear cell renal cell carcinomaOrgan cultureCell renal cell carcinomaExpression increasesAddition of TL1A
2021
MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells
Jeong J, Shin JH, Li W, Hong JY, Lim J, Hwang JY, Chung JJ, Yan Q, Liu Y, Choi J, Wysolmerski J. MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells. Cell Reports 2021, 37: 110160. PMID: 34965434, PMCID: PMC8762588, DOI: 10.1016/j.celrep.2021.110160.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBreast NeoplasmsCell ProliferationCytoskeletal ProteinsDrug Resistance, NeoplasmEndocytosisFemaleHumansMembrane MicrodomainsMyelin and Lymphocyte-Associated Proteolipid ProteinsPhosphoproteinsPlasma Membrane Calcium-Transporting ATPasesReceptor, ErbB-2Sodium-Hydrogen ExchangersTrastuzumabTumor Cells, CulturedConceptsLipid raft formationBreast cancer cellsLipid raftsLipid raft resident proteinsCancer cellsRaft formationRaft-resident proteinsProximity ligation assayProtein complexesMembrane protrusionsProtein interactionsPlasma membraneLigation assayMAL2Membrane stabilityStructural organizationPotential therapeutic targetPhysical interactionMembrane retentionProteinRaftsTherapeutic targetCellsIntracellular calcium concentrationLow intracellular calcium concentration
2019
Co-Expression of SYK and ZAP70 Subverts Negative B-Cell Selection and Enables Oncogenic Signaling in Multiple B-Cell Malignancies
Sadras T, Martin M, Kim-Sing L, Cutler J, Lenz G, Knapp A, Ghergus D, Delmotte F, Schleiss C, Korganow A, Soulas-Sprauel P, Chen Z, Pandey A, Weinstock D, Jumaa H, Meffre E, Martin T, Müschen M. Co-Expression of SYK and ZAP70 Subverts Negative B-Cell Selection and Enables Oncogenic Signaling in Multiple B-Cell Malignancies. Blood 2019, 134: 295. DOI: 10.1182/blood-2019-128999.Peer-Reviewed Original ResearchB-cell chronic lymphocytic leukemiaNegative B cell selectionB cellsB-cell malignanciesB cell selectionCo-expressing cellsT cellsBCR-stimulated B cellsZAP70 expressionMultiple B-cell malignanciesLymphoma cellsAutoreactive BCRsCentral tolerance checkpointsCell deathT cell populationsB cell compartmentChronic lymphocytic leukemiaProximity ligation assayB-cell lymphoma cellsMantle cell lymphomaTumor B cellsExpression of ZAP70Human B-cell lymphoma cellsImmature B cellsDevelopment of leukemiaInhibition of Heat Shock Protein 90 suppresses TWIST1 Transcription
Chong KY, Kang M, Garofalo F, Ueno D, Liang H, Cady S, Madarikan O, Pitruzzello N, Tsai CH, Hartwich T, Shuch B, Yang-Hartwich Y. Inhibition of Heat Shock Protein 90 suppresses TWIST1 Transcription. Molecular Pharmacology 2019, 96: 168-179. PMID: 31175180, DOI: 10.1124/mol.119.116137.Peer-Reviewed Original ResearchMeSH KeywordsBenzoquinonesCell Line, TumorDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHSP90 Heat-Shock ProteinsHumansKidney NeoplasmsLactams, MacrocyclicNasopharyngeal NeoplasmsNuclear ProteinsOvarian NeoplasmsPhosphorylationPromoter Regions, GeneticSTAT3 Transcription FactorTissue Array AnalysisTranscription, GeneticTwist-Related Protein 1ConceptsEpithelial-mesenchymal transitionHsp90 inhibitorsTwist1 transcriptionMolecular chaperone heat shock protein 90Chaperone heat shock protein 90Involvement of Hsp90Heat shock protein 90Cancer cell linesRole of Hsp90Binding of STAT3Inhibition of Hsp90Shock protein 90Cell linesProximity ligation assayHsp90 inhibitor 17TWIST1 mRNA expressionTranscription factorsSignal transducerProtein 90Promoter activityTranscription 3New therapeutic opportunitiesHsp90Molecular mechanismsSTAT3 activity
2017
Immune marker profiling and PD-L1, PD-L2 expression mechanisms across non-small cell lung cancer mutations.
Toki M, Mani N, Smithy J, Liu Y, Altan M, Wasserman B, Tuktamyshov R, Syrigos K, Rimm D. Immune marker profiling and PD-L1, PD-L2 expression mechanisms across non-small cell lung cancer mutations. Journal Of Clinical Oncology 2017, 35: 9076-9076. DOI: 10.1200/jco.2017.35.15_suppl.9076.Peer-Reviewed Original ResearchNon-small cell lung cancerEpidermal growth factor receptorPD-L1 expressionPD-L2 expressionPD-L1Stroma expressionTIL activationKRAS mutantPD-1/PD-L1 axis inhibitorsMutation statusResponse rateProximity ligation assayHigh PD-L1 levelsActivation statusProgrammed Death Ligand 1EGFR mutantsHigh PD-L1NSCLC patient tumorsTherapy response ratesPD-L1 levelsDeath ligand 1Cell lung cancerEGFR-mutant tumorsPD-L1 tumorsHigh response rate
2016
Methyltransferase-like protein 16 binds the 3′-terminal triple helix of MALAT1 long noncoding RNA
Brown JA, Kinzig CG, DeGregorio SJ, Steitz JA. Methyltransferase-like protein 16 binds the 3′-terminal triple helix of MALAT1 long noncoding RNA. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 14013-14018. PMID: 27872311, PMCID: PMC5150381, DOI: 10.1073/pnas.1614759113.Peer-Reviewed Original ResearchConceptsGel shift assaysMetastasis-associated lung adenocarcinoma transcript 1RNA triple helicesPutative RNA methyltransferaseCompetitive gel shift assaysRNA-protein interactionsRNA stability elementAbundant nuclear proteinNative gel shift assaysRich internal loopSitu proximity ligation assayTriple helixHEK293T cell lysatesStem-loop structureProximity ligation assayT cell lysatesRNA methyltransferaseVivo UVNucleotide compositionNuclear proteinsLung adenocarcinoma transcript 1RNA immunoprecipitationStability elementMETTL16Rich tractA proximity-dependent assay for specific RNA–protein interactions in intact cells
Zhang W, Xie M, Shu MD, Steitz JA, DiMaio D. A proximity-dependent assay for specific RNA–protein interactions in intact cells. RNA 2016, 22: 1785-1792. PMID: 27659050, PMCID: PMC5066630, DOI: 10.1261/rna.058248.116.Peer-Reviewed Original ResearchConceptsRNA-protein interactionsSpecific RNA-protein interactionsProximity ligation assayTarget RNAProtein-protein interactionsSame cellular compartmentCellular compartmentsRNA targetsIntact cellsLigation assayRNADiscrete compartmentsProteinDNA oligonucleotideFluorescent signalOligonucleotide complementaryCellsCompartmentsAssaysColocalizationHigh specificityInteractionStaining methodOligonucleotideAdaptationEGFR-GRB2 Protein Colocalization Is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma
Toki MI, Carvajal-Hausdorf DE, Altan M, McLaughlin J, Henick B, Schalper KA, Syrigos KN, Rimm DL. EGFR-GRB2 Protein Colocalization Is a Prognostic Factor Unrelated to Overall EGFR Expression or EGFR Mutation in Lung Adenocarcinoma. Journal Of Thoracic Oncology 2016, 11: 1901-1911. PMID: 27449805, PMCID: PMC5075503, DOI: 10.1016/j.jtho.2016.06.025.Peer-Reviewed Original ResearchConceptsEGFR pathway activationSeries of patientsLung adenocarcinomaMutation statusEGFR expressionPathway activationProximity ligation assayKRAS wild-type tumorsEGFR-mutant patientsKRAS-mutant casesCohort of patientsWild-type tumorsInteraction of EGFREGFR expression levelsEGFR protein expressionMAPK/ERK pathwayGrowth factor receptorActive EGFRPrognostic factorsDifferent mutation statusPatient groupPrognostic valueLonger survivalEGFR mutationsPrognostic marker
2015
The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3′ ends
Xie M, Zhang W, Shu MD, Xu A, Lenis DA, DiMaio D, Steitz JA. The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3′ ends. Genes & Development 2015, 29: 1552-1564. PMID: 26220997, PMCID: PMC4526738, DOI: 10.1101/gad.266973.115.Peer-Reviewed Original ResearchConceptsEnd processing signalsSmall nuclear RNAProximity ligation assayEnd processingPre-miRNAsHerpesvirus saimiriPre-miRNA hairpinsRNA-protein interactionsSitu proximity ligation assayIntegrator complexMiRNA 3MiRNA biogenesisSnRNA 3Primary miRNAMiRNA hairpinsIntegrator activityNuclear RNASequence downstreamOncogenic γ-herpesvirusesRescue experimentsLigation assayVivo knockdownComplex actsΓ-herpesvirusesHairpin
2014
Application of the Proximity-Dependent Assay and Fluorescence Imaging Approaches to Study Viral Entry Pathways
Lipovsky A, Zhang W, Iwasaki A, DiMaio D. Application of the Proximity-Dependent Assay and Fluorescence Imaging Approaches to Study Viral Entry Pathways. Methods In Molecular Biology 2014, 1270: 437-451. PMID: 25702134, DOI: 10.1007/978-1-4939-2309-0_30.Peer-Reviewed Original ResearchConceptsGenome-wide RNA interference screenEnriched gene categoriesConfirmation of phenotypesGenome-wide lossRNA interference screenVirus entryFunction genetic screenRNA interference studiesFluorescence imaging approachesProximity ligation assayGenetic screenGene categoriesInterference screenMembrane compartmentsIndividual genesBiochemical approachesCellular compartmentsMolecular intricaciesMicroscopy-based methodBioinformatics analysisProtein locationRNA interferenceCellular organellesViral entry pathwayCellular factorsA novel biomarker panel examining response to adjuvant pancreatic cancer therapy in RTOG 9704.
Heestand G, Murphy J, Moughan J, Regine W, Luo J, Graber M, Kunz P, Fisher G, Guha C, Lin B, Mowat R, Gaur R, Buyyounouski M, Chen Y, Chang D, Koong A. A novel biomarker panel examining response to adjuvant pancreatic cancer therapy in RTOG 9704. Journal Of Clinical Oncology 2014, 32: 176-176. DOI: 10.1200/jco.2014.32.3_suppl.176.Peer-Reviewed Original ResearchDisease-free survivalMatrix metalloproteinase-7RTOG 9704MMP-7 serum levelsProximity ligation assaySerum samplesBaseline serum specimensBaseline serum samplesResected stage ILevels of CEAPancreatic cancer patientsPancreatic cancer therapyNovel biomarker panelNational Cancer InstituteGEM armImproved OSEligible patientsOS benefitAdjuvant therapyGemcitabine chemotherapySerum levelsCA 19Cancer patientsClinical endpointsPancreatic cancer
2009
Identification of a biomarker panel using a multiplex proximity ligation assay improves accuracy of pancreatic cancer diagnosis
Chang ST, Zahn JM, Horecka J, Kunz PL, Ford JM, Fisher GA, Le QT, Chang DT, Ji H, Koong AC. Identification of a biomarker panel using a multiplex proximity ligation assay improves accuracy of pancreatic cancer diagnosis. Journal Of Translational Medicine 2009, 7: 105. PMID: 20003342, PMCID: PMC2796647, DOI: 10.1186/1479-5876-7-105.Peer-Reviewed Original ResearchConceptsPancreatic cancer diagnosisCA19-9Pancreatic cancerBiomarker panelProximity ligation assayOptimal biomarker panelCancer diagnosisPancreatic cancer patientsPancreatic ductal adenocarcinoma casesAge-matched controlsLogistic regression modelingCox survival modelsBackgroundPancreatic cancerClinical stagePrognostic significanceMultiplex proximity ligation assayCancer patientsPlasma biomarkersPlasma levelsAdenocarcinoma casesClinical cohortLigation assayDiagnosisCancerBiomarkers
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