Featured Publications
Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition
Gale M, Li Y, Cao J, Liu ZZ, Holmbeck MA, Zhang M, Lang SM, Wu L, Do Carmo M, Gupta S, Aoshima K, DiGiovanna MP, Stern DF, Rimm DL, Shadel GS, Chen X, Yan Q. Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition. Cancer Research 2020, 80: 524-535. PMID: 31690671, PMCID: PMC7002225, DOI: 10.1158/0008-5472.can-18-3985.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBreast NeoplasmsCell ProliferationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHumansMiceMice, Inbred NODMice, SCIDMitochondrial Proton-Translocating ATPasesOligomycinsReceptor, ErbB-2TrastuzumabTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsResistant cellsHER2-Targeted TherapyTrastuzumab-resistant tumorsNew therapeutic strategiesNovel potential targetDrug-free mediumAntibody therapySynthase inhibitionLow doseTherapeutic strategiesTrastuzumabBreast tumorsHER2TherapyAcquired ResistanceTumorsPotential targetMitochondrial respirationCellsSelective dependencyInhibitionMinimal changesNovel vulnerabilitiesATP synthase inhibitionOligomycin AKDM5 histone demethylases repress immune response via suppression of STING
Wu L, Cao J, Cai WL, Lang SM, Horton JR, Jansen DJ, Liu ZZ, Chen JF, Zhang M, Mott BT, Pohida K, Rai G, Kales SC, Henderson MJ, Hu X, Jadhav A, Maloney DJ, Simeonov A, Zhu S, Iwasaki A, Hall MD, Cheng X, Shadel GS, Yan Q. KDM5 histone demethylases repress immune response via suppression of STING. PLOS Biology 2018, 16: e2006134. PMID: 30080846, PMCID: PMC6095604, DOI: 10.1371/journal.pbio.2006134.Peer-Reviewed Original ResearchConceptsImmune responseSTING expressionCyclic GMP-AMP synthase stimulatorSuppression of STINGCancer cellsCancer immunotherapy agentsHuman papilloma virusAdaptive immune responsesMultiple clinical trialsExpression of STINGBreast cancer cellsInnate immune defenseRobust interferon responseMultiple cancer typesIntratumoral CD8Immunotherapy agentsAnticancer immunotherapyPatient survivalNeck cancerPapilloma virusClinical trialsT cellsSTING agonistsKDM5 histonePositive headKDM5 lysine demethylases are involved in maintenance of 3′UTR length
Blair LP, Liu Z, Labitigan RL, Wu L, Zheng D, Xia Z, Pearson EL, Nazeer FI, Cao J, Lang SM, Rines RJ, Mackintosh SG, Moore CL, Li W, Tian B, Tackett AJ, Yan Q. KDM5 lysine demethylases are involved in maintenance of 3′UTR length. Science Advances 2016, 2: e1501662. PMID: 28138513, PMCID: PMC5262454, DOI: 10.1126/sciadv.1501662.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsBreast NeoplasmsCyclin D1DEAD-box RNA HelicasesFemaleHumansJumonji Domain-Containing Histone DemethylasesMCF-7 CellsNeoplasm ProteinsNuclear ProteinsRepressor ProteinsRetinoblastoma-Binding Protein 2Ribonuclease IIISaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsConceptsAlternative mRNA formsLysine demethylasesLysine demethylasePolyadenylation sitesJhd2Novel roleProcessing machineryKDM5B expressionMRNA formsBreast cancer cellsDemethylasesTargetable mechanismHuman breast tumor tissuesKDM5BProtein expressionCancer cellsKDM5AGenesCritical roleBreast tumor tissuesCellsExpressionChromatinSaccharomycesDemethylaseMitochondrial DNA stress primes the antiviral innate immune response
West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, Bestwick M, Duguay BA, Raimundo N, MacDuff DA, Kaech SM, Smiley JR, Means RE, Iwasaki A, Shadel GS. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 2015, 520: 553-557. PMID: 25642965, PMCID: PMC4409480, DOI: 10.1038/nature14156.Peer-Reviewed Original ResearchKaposi’s Sarcoma-Associated Herpesvirus K3 and K5 Proteins Down Regulate Both DC-SIGN and DC-SIGNR
Lang SM, Bynoe MO, Karki R, Tartell MA, Means RE. Kaposi’s Sarcoma-Associated Herpesvirus K3 and K5 Proteins Down Regulate Both DC-SIGN and DC-SIGNR. PLOS ONE 2013, 8: e58056. PMID: 23460925, PMCID: PMC3584050, DOI: 10.1371/journal.pone.0058056.Peer-Reviewed Original ResearchAmino Acid MotifsCell Adhesion MoleculesCell MembraneDown-RegulationEndocytosisHEK293 CellsHerpesvirus 8, HumanHumansImmunoprecipitationLectins, C-TypeLysosomesProteasome Endopeptidase ComplexProtein StabilityProtein Structure, TertiaryProteolysisReceptors, Cell SurfaceStructure-Activity RelationshipTyrosineUbiquitinationViral Proteins
2022
CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression
Zhang M, Liu ZZ, Aoshima K, Cai WL, Sun H, Xu T, Zhang Y, An Y, Chen JF, Chan LH, Aoshima A, Lang SM, Tang Z, Che X, Li Y, Rutter SJ, Bossuyt V, Chen X, Morrow JS, Pusztai L, Rimm DL, Yin M, Yan Q. CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression. Science Translational Medicine 2022, 14: eabf5473. PMID: 35108062, PMCID: PMC9003667, DOI: 10.1126/scitranslmed.abf5473.Peer-Reviewed Original ResearchConceptsBreast cancer metastasisReticuloendotheliosis viral oncogene homolog ACancer metastasisImmune suppressionM2 macrophagesWorse metastasis-free survivalMetastatic breast cancerMetastasis-free survivalV-rel avian reticuloendotheliosis viral oncogene homolog ACancer-related deathPrimary breast tumorsMultiple mouse modelsNF-κB signalingImmunocompetent settingNuclear factor-κB family membersMetastasis-promoting genesDistant metastasisMetastatic sitesPrimary tumorEffective therapyBreast cancerMetastasis treatmentMouse modelBreast tumorsMetastasis
2006
A Genetic System for Rhesus Monkey Rhadinovirus: Use of Recombinant Virus To Quantitate Antibody-Mediated Neutralization
Bilello J, Morgan J, Damania B, Lang S, Desrosiers R. A Genetic System for Rhesus Monkey Rhadinovirus: Use of Recombinant Virus To Quantitate Antibody-Mediated Neutralization. Journal Of Virology 2006, 80: 1549-1562. PMID: 16415030, PMCID: PMC1346924, DOI: 10.1128/jvi.80.3.1549-1562.2006.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseAnimalsAntibodies, ViralBase SequenceCell LineCloning, MolecularCosmidsDNA, ViralGene LibraryGenes, ReporterGenome, ViralGreen Fluorescent ProteinsHerpesviridae InfectionsHumansMacaca mulattaNeutralization TestsRecombination, GeneticRhadinovirusTumor Virus InfectionsConceptsRhesus monkey rhadinovirusGreen fluorescent proteinGenetic systemRhesus monkey fibroblastsGFP reporter geneMonkey fibroblastsGamma-2 herpesvirusKaposi's sarcoma-associated herpesvirusDifferent cell typesGenome reconstitutionSarcoma-associated herpesvirusCosmid clonesTerminal repeat regionR1 geneReporter geneRepeat regionFluorescent proteinExpression cassetteCell typesSEAP activityRRV infectivityRecombinant virusesGenomeB cellsGenes
2002
The First HxRxG Motif in Simian Immunodeficiency Virus mac239 Vpr Is Crucial for G2/M Cell Cycle Arrest
Mueller S, Lang S. The First HxRxG Motif in Simian Immunodeficiency Virus mac239 Vpr Is Crucial for G2/M Cell Cycle Arrest. Journal Of Virology 2002, 76: 11704-11709. PMID: 12388729, PMCID: PMC136740, DOI: 10.1128/jvi.76.22.11704-11709.2002.Peer-Reviewed Original ResearchConceptsCell cycle arrestCell cycle arrest functionCycle arrestArrest functionVpr mutantsAlpha-helical domainAlpha-helical regionG2/M cell cycle arrestLong terminal repeatM cell cycle arrestNuclear importArrest of cellsSIV long terminal repeatTranscriptional transactivationPreintegration complexSecond motifFunctional domainsReduced transactivationVpr proteinTerminal repeatAmino acidsTransactivationSingle substitutionMotifMutantsExperimentelle Untersuchungen zu Gentherapie und Gentransfer bei Kopf-Hals-Karzinomen im Rahmen eines multimodalen Therapiekonzeptes
Lang S. Experimentelle Untersuchungen zu Gentherapie und Gentransfer bei Kopf-Hals-Karzinomen im Rahmen eines multimodalen Therapiekonzeptes. Laryngo-Rhino-Otologie 2002, 81: 534-536. PMID: 12173066, DOI: 10.1055/s-2002-33283.Peer-Reviewed Original ResearchDie Expression der ζ-Kette des T-Zell-Rezeptors als Prognosemarker bei Kopf-Hals-Karzinomen
Müller D, Lang S, Roskrow M, Wollenberg B. Die Expression der ζ-Kette des T-Zell-Rezeptors als Prognosemarker bei Kopf-Hals-Karzinomen. Laryngo-Rhino-Otologie 2002, 81: 516-520. PMID: 12173063, DOI: 10.1055/s-2002-33289.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesZeta chain expressionPeripheral blood lymphocytesT cell receptorTumor stageZeta chainCorrelated to clinical dataMechanisms of immune suppressionT cell receptor zeta chainSystemic immune defectsAnti-tumor responsesEarly tumor stageHigher tumor stageSquamous cell carcinomaHead and neckT cell activationFlow cytometric analysisSystemic immunomodulationImmune defectsInfiltrating lymphocytesClinical aggressivenessCell carcinomaImmune suppressionBlood lymphocytesSCCHNZur Aussagefähigkeit koronarer Sekundärrekonstruktionen computertomographischer Sequenzen der Nasennebenhöhlen
Lang S, Jäger L, Grevers G. Zur Aussagefähigkeit koronarer Sekundärrekonstruktionen computertomographischer Sequenzen der Nasennebenhöhlen. Laryngo-Rhino-Otologie 2002, 81: 418-421. PMID: 12063628, DOI: 10.1055/s-2002-32212.Peer-Reviewed Original ResearchConceptsMultidetector computed tomographyAnterior skull baseCoronal reconstructionsConventional CTComputed tomographySkull baseParanasal sinusesSinus surgeryCT evaluationElderly patientsCoronal scansDiagnostic evaluationComplex anatomyCoronal imagesCoronal sectionsCT generationAnatomical landmarksCT imagesSinusPatientsTomographyStandard procedureSurgeryMultidetectorKorrelation von FDG-PET und MRT/CT mit der Histopathologie in Primärdiagnostik, Lymphknotenstaging und Rezidivdiagnostik von Kopf-Hals-Tumoren
Pöpperl G, Lang S, Dagdelen O, Jäger L, Tiling R, Hahn K, Tatsch K. Korrelation von FDG-PET und MRT/CT mit der Histopathologie in Primärdiagnostik, Lymphknotenstaging und Rezidivdiagnostik von Kopf-Hals-Tumoren. RöFo 2002, 174: 714-720. PMID: 12063600, DOI: 10.1055/s-2002-32215.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedDiagnosis, DifferentialFemaleFluorodeoxyglucose F18HumansLymph NodesLymphatic MetastasisMagnetic Resonance ImagingMaleMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingNeoplasms, Unknown PrimaryOtorhinolaryngologic NeoplasmsPrognosisRetrospective StudiesSensitivity and SpecificityTomography, Emission-ComputedTomography, X-Ray ComputedConceptsLymph node metastasisCervical lymph node metastasisDiagnosis of primary tumorLymph node involvementPrimary tumorPre-surgical diagnosisTumor recurrenceNode metastasisFDG-PETNode involvementPrimary lesionHistopathological findingsDiagnostic value of FDG-PETStaging of head and neck cancerPrimary lymph node involvementDiagnosis of tumor recurrenceHead and neck cancerTumor diameter <Occult primary tumorDetect tumor recurrenceMorphological imaging modalitiesRecurrent tumorsPT1 stageNeck cancerPatient prognosisKaposi's sarcoma associated herpesvirus immune evasion strategies.
Means R, Lang S, Chung Y, Jung J. Kaposi's sarcoma associated herpesvirus immune evasion strategies. Frontiers In Bioscience-Landmark 2002, 7: e185-203. PMID: 11991843, DOI: 10.2741/a915.Peer-Reviewed Original Research
2000
Simian Immunodeficiency Virus Containing Mutations in N-Terminal Tyrosine Residues and in the PxxP Motif in Nef Replicates Efficiently in Rhesus Macaques
Carl S, Iafrate A, Lang S, Stolte N, Stahl-Hennig C, Mätz-Rensing K, Fuchs D, Skowronski J, Kirchhoff F. Simian Immunodeficiency Virus Containing Mutations in N-Terminal Tyrosine Residues and in the PxxP Motif in Nef Replicates Efficiently in Rhesus Macaques. Journal Of Virology 2000, 74: 4155-4164. PMID: 10756028, PMCID: PMC111930, DOI: 10.1128/jvi.74.9.4155-4164.2000.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesCD4 AntigensCell Line, TransformedCOS CellsDown-RegulationGene Products, nefHistocompatibility Antigens Class IHumansMacaca mulattaMutagenesisP21-Activated KinasesPhosphorylationProtein Serine-Threonine KinasesSimian immunodeficiency virusSrc Homology DomainsTyrosineViral LoadVirus ReplicationConceptsAbility of NefTyrosine-based endocytosis signalTyrosine residuesHigh viral loadCellular signal transductionTyrosine kinase SrcNef functionViral loadEndocytosis signalEndocytic machineryPXXP motifN-terminal tyrosine residueCell surface expressionKinase SrcKinase assaysSignal transductionProline residuesClass I major histocompatibility complexN-terminal tyrosineI major histocompatibility complexLigand domainCombined mutationsNef interactionsMajor histocompatibility complexMutations
1997
Association of simian immunodeficiency virus Nef with cellular serine/threonine kinases is dispensable for the development of AIDS in rhesus macaques
Lang S, Lafrate A, Stahl-Hennig C, Kuhn E, Nisslein T, Kaup F, Haupt M, Hunsmann G, Skowronski J, Kirchhoff F. Association of simian immunodeficiency virus Nef with cellular serine/threonine kinases is dispensable for the development of AIDS in rhesus macaques. Nature Medicine 1997, 3: 860-865. PMID: 9256276, DOI: 10.1038/nm0897-860.Peer-Reviewed Original ResearchConceptsCellular serine/threonine kinaseSerine/threonine kinaseThreonine kinaseTyrosine kinase SrcPutative SH3Simian immunodeficiency virus NefKinase SrcMutant formsEfficient replicationKinaseInduction of AIDSSimian immunodeficiency virusNef geneCD4 downregulationSIVmac NefRhesus macaquesRapid deathNef sequencesSH3NefSrcGenesDomainDifferent time pointsPathogenicity
1995
Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri
Jung J, Lang S, Jun T, Roberts T, Veillette A, Desrosiers R. Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri. Journal Of Virology 1995, 69: 7814-7822. PMID: 7494293, PMCID: PMC189725, DOI: 10.1128/jvi.69.12.7814-7822.1995.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceCell LineCell Line, TransformedCloning, MolecularDNA PrimersElectrophoresis, Polyacrylamide GelGene ExpressionHerpesvirus 2, SaimiriineHumansLymphocyte Specific Protein Tyrosine Kinase p56(lck)Molecular Sequence DataMolecular WeightPhosphoproteinsPlasmidsPolymerase Chain ReactionRecombinant Fusion ProteinsSignal TransductionSrc-Family KinasesT-LymphocytesTumor Cells, CulturedViral ProteinsConceptsExpression of tipSignal transductionTyrosine phosphorylationT cell signal transductionCellular signal transductionCellular tyrosine phosphorylationHuman Jurkat T cell lineJurkat T cell lineJurkat T cellsInhibition of LckSH3 domainLckTransductionHerpesvirus saimiriFibroblast cellsPhosphorylationStable complexesSurface expressionBinding assaysComplex formationExpressionCellsAnti-CD3 stimulationT cellsB cells