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
2012
The PreAmplifier ShAper for the ALICE TPC detector
Soltveit H, Stachel J, Braun-Munzinger P, Musa L, Gustafsson H, Bonnes U, Oeschler H, Osterman L, Lang S, Collaboration F. The PreAmplifier ShAper for the ALICE TPC detector. Nuclear Instruments And Methods In Physics Research Section A Accelerators Spectrometers Detectors And Associated Equipment 2012, 676: 106-119. DOI: 10.1016/j.nima.2012.02.012.Peer-Reviewed Original ResearchTime projection chamberCharge sensitive amplifierALICE Time Projection ChamberPb-Pb collisionsPole-zero networkEquivalent noise chargeFront-end cardsProjection chamberTPC detectorALICE experimentDetector capacitanceNoise chargeSensitive amplifierAlicePreamplifierDetectorP-PIdentical channelsInput capacitanceIntegral non-linearityYears of operationShaperBias networkChargeLHC
2011
Corrections: Viral Infection of the Placenta Leads to Fetal Inflammation and Sensitization to Bacterial Products Predisposing to Preterm Labor
Cardenas I, Means R, Aldo P, Koga K, Lang S, Booth C, Manzur A, Oyarzun E, Romero R, Mor G. Corrections: Viral Infection of the Placenta Leads to Fetal Inflammation and Sensitization to Bacterial Products Predisposing to Preterm Labor. The Journal Of Immunology 2011, 187: 2835-2835. DOI: 10.4049/jimmunol.1190048.Peer-Reviewed Original Research
2010
The Kaposi's sarcoma-associated herpesvirus E3 ubiquitin ligase K5 acts as a novel oncogene, altering cellular metabolism and signaling: implications for tumorigenesis
Karki R, Lang S, Means R. The Kaposi's sarcoma-associated herpesvirus E3 ubiquitin ligase K5 acts as a novel oncogene, altering cellular metabolism and signaling: implications for tumorigenesis. Infectious Agents And Cancer 2010, 5: a79. PMCID: PMC3002742, DOI: 10.1186/1750-9378-5-s1-a79.Peer-Reviewed Original ResearchViral infection sensitizes pregnancy to LPS leading to preterm labor
Cardenas I, Aldo P, Means R, Lang S, Stabach P, Mor G. Viral infection sensitizes pregnancy to LPS leading to preterm labor. Journal Of Reproductive Immunology 2010, 86: 33. DOI: 10.1016/j.jri.2010.06.061.Peer-Reviewed Original Research
2008
Vaccine Protection by Live, Attenuated Simian Immunodeficiency Virus in the Absence of High-Titer Antibody Responses and High-Frequency Cellular Immune Responses Measurable in the Periphery
Mansfield K, Lang S, Gauduin M, Sanford H, Lifson J, Johnson R, Desrosiers R. Vaccine Protection by Live, Attenuated Simian Immunodeficiency Virus in the Absence of High-Titer Antibody Responses and High-Frequency Cellular Immune Responses Measurable in the Periphery. Journal Of Virology 2008, 82: 4135-4148. PMID: 18272584, PMCID: PMC2292994, DOI: 10.1128/jvi.00015-08.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralInterferon-gammaIntestinal MucosaLymphoid TissueMacaca mulattaNeutralization TestsRetroviridae ProteinsRNA, ViralSAIDS VaccinesSequence DeletionSimian Acquired Immunodeficiency SyndromeSimian immunodeficiency virusT-LymphocytesVaccines, AttenuatedViral Envelope ProteinsViral LoadViremiaConceptsAnti-SIV antibody responsesSimian immunodeficiency virusAntibody responseImmune responseVaccine protectionImmunodeficiency virusCopies/Gamma interferon enzyme-linked immunospotVaccine/challenge experimentsAttenuated simian immunodeficiency virusGut-associated lymphoid tissueHigh-titer antibody responsesAnti-SIV immune responsesEnzyme-linked immunospotMacrophage marker CD68Cellular immune responsesHumoral immune responseViral load measurementsWeeks of infectionNeutralization-resistant strainDouble-labeling experimentsVaccinated monkeysViral loadPeripheral bloodLymphoid tissue
2007
Human gammaherpesvirus immune evasion strategies
Means R, Lang S, Jung J. Human gammaherpesvirus immune evasion strategies. 2007, 559-586. DOI: 10.1017/cbo9780511545313.032.Peer-Reviewed Original ResearchEpstein-Barr virusMulticentric Castleman's diseasePrimary effusion lymphomaImmune systemKaposi's sarcoma-associated herpesvirusKaposi's sarcomaImmune responsePersistent infectionNasopharyngeal carcinomaInnate responseSarcoma-associated herpesvirusHemophagocytic lymphohistiocytosis syndromeNatural killer cellsNormal immune systemClearance of infectionImmune evasion strategiesInfectious mononucleosisImmunocompromised hostHodgkin's diseaseKiller cellsImmunocompetent hostsCastleman's diseaseHHV-4HHV-8Gastric cancer
2006
Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus
Kaur A, Sanford H, Garry D, Lang S, Klumpp S, Watanabe D, Bronson R, Lifson J, Rosati M, Pavlakis G, Felber B, Knipe D, Desrosiers R. Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus. Virology 2006, 357: 199-214. PMID: 16962628, PMCID: PMC1819472, DOI: 10.1016/j.virol.2006.08.007.Peer-Reviewed Original ResearchConceptsSimian immunodeficiency virusELISPOT responsesImmunodeficiency virusHSV vectorsHerpes simplex virus vectorsPlasma SIV RNAPlasma viremia levelsVector-based vaccinesDay of challengeSimplex virus vectorsNef fusion proteinRecombinant HSV vectorsSIV RNAIntravenous challengeViremia levelsAntibody titersVaccine approachesImmune responseRhesus macaquesProtective capacityMacaquesRecombinant herpesvirusDNA vectorsFusion proteinEnvInfection and Persistence of Rhesus Monkey Rhadinovirus in Immortalized B-Cell Lines
Bilello J, Lang S, Wang F, Aster J, Desrosiers R. Infection and Persistence of Rhesus Monkey Rhadinovirus in Immortalized B-Cell Lines. Journal Of Virology 2006, 80: 3644-3649. PMID: 16537632, PMCID: PMC1440374, DOI: 10.1128/jvi.80.7.3644-3649.2006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternB-LymphocytesCell Culture TechniquesCell Line, TransformedCell NucleusCell Transformation, ViralFibroblastsGenes, ReporterGenome, ViralGreen Fluorescent ProteinsHerpesviridae InfectionsHerpesvirus 4, HumanIn Situ Hybridization, FluorescenceMacaca mulattaRecombinant ProteinsRhadinovirusTime FactorsTumor Virus InfectionsVirus ReplicationA 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
2005
Immunization of Macaques with Single-Cycle Simian Immunodeficiency Virus (SIV) Stimulates Diverse Virus-Specific Immune Responses and Reduces Viral Loads after Challenge with SIVmac239
Evans D, Bricker J, Sanford H, Lang S, Carville A, Richardson B, Piatak M, Lifson J, Mansfield K, Desrosiers R. Immunization of Macaques with Single-Cycle Simian Immunodeficiency Virus (SIV) Stimulates Diverse Virus-Specific Immune Responses and Reduces Viral Loads after Challenge with SIVmac239. Journal Of Virology 2005, 79: 7707-7720. PMID: 15919923, PMCID: PMC1143664, DOI: 10.1128/jvi.79.12.7707-7720.2005.Peer-Reviewed Original ResearchConceptsSingle-Cycle Simian Immunodeficiency VirusesRNA copies/AIDS vaccine approachSingle-cycle SIVEnzyme-linked immunospotViral loadSimian immunodeficiency virusCopies/Immunodeficiency virusVaccine approachesGamma interferon enzyme-linked immunospotGag-specific T-cell responsesVirus-specific immune responsesMajor Histocompatibility Complex Class I DownregulationT cell proliferative responsesImmunization of macaquesPlasma viral loadT cell responsesMHC class IThird doseChronic phasePeripheral bloodWeek 8Immune responseControl animalsKaon and pion emission in asymmetric C+Au and Au+C collisions at 1.0A GeV and 1.8A GeV
Schmah A, Lang S, Böttcher I, Dohrmann F, Förster A, Grosse E, Koczoń P, Kohlmeyer B, Laue F, Menzel M, Naumann L, Oeschler H, Scheinast W, Schuck T, Schwab E, Senger P, Shin Y, Ströbele H, Sturm C, Surówska G, Uhlig F, Wagner A, Waluś W, Fuchs C, Faessler A, Mansour H. Kaon and pion emission in asymmetric C+Au and Au+C collisions at 1.0A GeV and 1.8A GeV. Physical Review C 2005, 71: 064907. DOI: 10.1103/physrevc.71.064907.Peer-Reviewed Original ResearchNuclear equation of stateSymmetric collision systemsTransport model calculationsEquation of stateK+ mesonsNuclear equationPeripheral collisionsPion emissionCollision systemsIncident energyAu nucleiC nucleiMesonsModel calculationsGeVCollisionCentral reactionPT-IGeV.PionEmissionRapidityCalculationsEnergyNucleusReview of the results of the KaoS Collaboration
Förster A, Collaboration T, Böttcher <, Dohrmann F, Förster A, Grosse E, Koczoń P, Kohlmeyer B, Lang S, Laue F, Menzel M, Naumann L, Oeschler H, Płoskoń M, Pühlhofer F, Scheinast W, Schmah A, Schuck T, Schwab E, Senger P, Shin Y, Ströbele H, Sturm C, Uhlig F, Wagner A, Waluś W. Review of the results of the KaoS Collaboration. Journal Of Physics G Nuclear And Particle Physics 2005, 31: s693. DOI: 10.1088/0954-3899/31/6/009.Peer-Reviewed Original ResearchCollision centralityK mesonsBeam energySoft nuclear equation-of-stateNuclear equation-of-stateDecreasing beam energyHeavy-ion collisionsK-/K+ ratioProduction of K+Polar emission anglePolar emission patternsEquation-of-stateC+C reactionsKaon energyKaoS CollaborationStrangeness exchangeK+ mesonsHeavy-ionCollision systemsExcitation functionsReaction planeK emissionEmission angleIncident energyAzimuthal distribution
2004
Impact of Nef-Mediated Downregulation of Major Histocompatibility Complex Class I on Immune Response to Simian Immunodeficiency Virus
Swigut T, Alexander L, Morgan J, Lifson J, Mansfield K, Lang S, Johnson R, Skowronski J, Desrosiers R. Impact of Nef-Mediated Downregulation of Major Histocompatibility Complex Class I on Immune Response to Simian Immunodeficiency Virus. Journal Of Virology 2004, 78: 13335-13344. PMID: 15542684, PMCID: PMC525019, DOI: 10.1128/jvi.78.23.13335-13344.2004.Peer-Reviewed Original ResearchConceptsSimian immunodeficiency virusHuman immunodeficiency virusImmunodeficiency virusWeeks postinfectionMajor Histocompatibility Complex Class I DownregulationClass IMajor histocompatibility complex class IHistocompatibility complex class IComplex class IMHC class INef gene productParental wild-type virusImmune responseLymphocyte activationWild-type virusNef functionCD4 downregulationFunctional activityMHC downregulationDownregulationResponse-4VirusMonkeysPostinfectionNefVpx proteins of SIVmac239 and HIV-2ROD interact with the cytoskeletal protein α-actinin 1
Mueller S, Jung R, Weiler S, Lang S. Vpx proteins of SIVmac239 and HIV-2ROD interact with the cytoskeletal protein α-actinin 1. Journal Of General Virology 2004, 85: 3291-3303. PMID: 15483243, DOI: 10.1099/vir.0.80198-0.Peer-Reviewed Original ResearchMeSH KeywordsActininAmino Acid SequenceAnimalsBiological TransportChlorocebus aethiopsCOS CellsCytoplasmHIV-2Molecular Sequence DataProlineProtein Structure, TertiaryRetroviridae ProteinsSequence AlignmentSimian immunodeficiency virusTransfectionTwo-Hybrid System TechniquesViral Regulatory and Accessory ProteinsConceptsPre-integration complexNuclear localization signalNuclear importProline-rich C-terminal domainClassical import pathwayEfficient nuclear importTwo-hybrid screenAlpha-actinin 1Α-actinin 1C-terminal domainLoss of interactionImport pathwayLocalization signalCellular proteinsNuclear localizationSequence elementsCytoskeletal proteinsVpx geneVpx proteinsQuiescent cellsAA proteinViral proteinsProteinVirion particlesRed-capped mangabeys