2024
Expression of Random Sequences and de novo Evolved Genes From the Mouse in Human Cells Reveals Functional Diversity and Specificity
Aldrovandi S, Castro J, Ullrich K, Karger A, Luria V, Tautz D. Expression of Random Sequences and de novo Evolved Genes From the Mouse in Human Cells Reveals Functional Diversity and Specificity. Genome Biology And Evolution 2024, 16: evae175. PMID: 39663928, PMCID: PMC11635099, DOI: 10.1093/gbe/evae175.Peer-Reviewed Original ResearchConceptsOpen reading frameGene open reading frameCellular regulatory pathwaysNoncoding DNAReading frameHuman cell linesHuman genomeAlpha-helicesGrowth experimentsCellular physiologyFunctional diversityPositive selectionBeta-sheetTranscriptomic responseRegulatory pathwaysAdaptive advantageHuman cellsGenesCell clonesCell linesSequenceClonesRandom sequencePathwayCells
2023
Epigenetic markers and therapeutic targets for metastasis
Kravitz C, Yan Q, Nguyen D. Epigenetic markers and therapeutic targets for metastasis. Cancer And Metastasis Reviews 2023, 42: 427-443. PMID: 37286865, PMCID: PMC10595046, DOI: 10.1007/s10555-023-10109-y.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEpigenomic alterationsLineage integrityTherapeutic targetEpigenetic markersCancer cellsGenetic aberrationsCurrent knowledgeHuman tumorsMalignant cell cloneTumor progressionDNANumber of discoveriesCell clonesDisseminated diseaseCertain organsPrimary tumorTherapeutic responseMetastatic cancerEpigenomeChromatinHistonesLiquid biopsyAlterationsClonesTargetGraft-versus-host disease is locally maintained in target tissues by resident progenitor-like T cells
Sacirbegovic F, Günther M, Greco A, Zhao D, Wang X, Zhou M, Rosenberger S, Oberbarnscheidt M, Held W, McNiff J, Jain D, Höfer T, Shlomchik W. Graft-versus-host disease is locally maintained in target tissues by resident progenitor-like T cells. Immunity 2023, 56: 369-385.e6. PMID: 36720219, PMCID: PMC10182785, DOI: 10.1016/j.immuni.2023.01.003.Peer-Reviewed Original ResearchConceptsHost diseaseAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationChronic antigen stimulationStem cell transplantationAlloreactive effectorsAdoptive transferCell transplantationΑβ TAntigen stimulationCell exhaustionGVHDRecipient tissuesEffector poolMajor causeCell clonesTarget tissuesAffected tissuesDiseaseGraftTissueTCF-1CellsDiseased tissuesMorbidity
2022
Application of B cell immortalization for the isolation of antibodies and B cell clones from vaccine and infection settings
Boswell K, Watkins T, Cale E, Samsel J, Andrews S, Ambrozak D, Driscoll J, Messina M, Narpala S, Hopp C, Cagigi A, Casazza J, Yamamoto T, Zhou T, Schief W, Crompton P, Ledgerwood J, Connors M, Gama L, Kwong P, McDermott A, Mascola J, Koup R. Application of B cell immortalization for the isolation of antibodies and B cell clones from vaccine and infection settings. Frontiers In Immunology 2022, 13: 1087018. PMID: 36582240, PMCID: PMC9794141, DOI: 10.3389/fimmu.2022.1087018.Peer-Reviewed Original ResearchConceptsB cell subsetsB cell clonesB-cell immortalizationMemory B cellsB cellsCell subsetsCell clonesHIV-1 infected individualsMemory B cell subsetsDifferent B cell populationsIsolation of antibodiesRecent malaria infectionFuture vaccine designCell immortalizationB cell populationsB cell survivalMalaria infectionPrimary B cellsVaccine settingInfection settingsImmunoglobulin secretionHealthy individualsTonsil tissueAntibody secretionBCL-6Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy
Fichtner ML, Hoehn KB, Ford EE, Mane-Damas M, Oh S, Waters P, Payne AS, Smith ML, Watson CT, Losen M, Martinez-Martinez P, Nowak RJ, Kleinstein SH, O’Connor K. Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy. Acta Neuropathologica Communications 2022, 10: 154. PMID: 36307868, PMCID: PMC9617453, DOI: 10.1186/s40478-022-01454-0.Peer-Reviewed Original ResearchConceptsB cell depletion therapyB cell clonesMuSK-MG patientsMyasthenia gravisB cellsMG patientsDepletion therapyCell clonesAutoantibody-producing B cellsMuscle-specific tyrosine kinaseComplete stable remissionB cell receptor repertoireCell receptor repertoireValuable candidate biomarkersB cell receptorMG relapseClinical relapseStable remissionDisease relapseAutoimmune disordersRelapsePatientsAcetylcholine receptorsCandidate biomarkersReceptor repertoireInhibition of a Chromatin and Transcription Modulator, SLTM, Increases HIV-1 Reactivation Identified by a CRISPR Inhibition Screen
Pedersen SF, Collora JA, Kim RN, Yang K, Razmi A, Catalano AA, Yeh YJ, Mounzer K, Tebas P, Montaner LJ, Ho YC. Inhibition of a Chromatin and Transcription Modulator, SLTM, Increases HIV-1 Reactivation Identified by a CRISPR Inhibition Screen. Journal Of Virology 2022, 96: e00577-22. PMID: 35730977, PMCID: PMC9278143, DOI: 10.1128/jvi.00577-22.Peer-Reviewed Original ResearchConceptsHIV-1-infected cellsHIV-1 reactivationT cell clonesHIV-1HIV-1 protein expressionAntiretroviral therapyDrug treatmentProtein expressionInfected cellsInfected individualsHIV-1-infected individualsCell clonesEffective antiretroviral therapyHIV-1 cureLong-term therapyHIV-1 gene expressionHIV-1 persistenceHIV-1 provirusHIV-1 transcriptionImmune cell killingNovel therapeutic targetCell deathLatent reservoirImmune cellsT cellsSingle-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones
Collora JA, Liu R, Pinto-Santini D, Ravindra N, Ganoza C, Lama JR, Alfaro R, Chiarella J, Spudich S, Mounzer K, Tebas P, Montaner LJ, van Dijk D, Duerr A, Ho YC. Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones. Immunity 2022, 55: 1013-1031.e7. PMID: 35320704, PMCID: PMC9203927, DOI: 10.1016/j.immuni.2022.03.004.Peer-Reviewed Original ResearchConceptsHIV-1 eradicationHIV-1 RNAHIV-1Effector memory Th1 cellsHIV-1-infected individualsHIV-1-infected CD4Clonal expansionCell clonesMemory Th1 cellsCell clonal expansionPersistent antigenAntiretroviral therapyViral suppressionCytotoxic CD4Cytotoxic TTh1 cellsAntigen stimulationClonal expansion dynamicsUninfected individualsSurface protein expressionTNF responseUnstimulated conditionsTCR sequencesProtein expressionCD4Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
2020
Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis
Jiang R, Hoehn KB, Lee CS, Pham MC, Homer RJ, Detterbeck FC, Aban I, Jacobson L, Vincent A, Nowak RJ, Kaminski HJ, Kleinstein SH, O'Connor KC. Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 30649-30660. PMID: 33199596, PMCID: PMC7720237, DOI: 10.1073/pnas.2007206117.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAutoantibodiesB-LymphocytesBiomarkersClonal EvolutionClonal Selection, Antigen-MediatedDisease SusceptibilityFemaleHumansLymphocyte CountMaleMiddle AgedModels, BiologicalMyasthenia GravisRadioimmunoassayReceptors, CholinergicThymectomyThymus GlandV(D)J RecombinationYoung AdultConceptsB cell clonesMyasthenia gravisB cell repertoireB cellsCell clonesPlasma cellsCell repertoireAdditional immunosuppressive treatmentDiminished clinical responseThymic lymphofollicular hyperplasiaComplete stable remissionMajority of patientsAntigen-experienced B cellsRandomized clinical trialsClinical symptom measuresAChR autoantibodiesImmunosuppressive treatmentSteroid doseAutoantibody titersMG thymusClinical responseStable remissionClinical scoresAutoimmune diseasesClinical trialsHuman germinal centres engage memory and naive B cells after influenza vaccination
Turner JS, Zhou JQ, Han J, Schmitz AJ, Rizk AA, Alsoussi WB, Lei T, Amor M, McIntire KM, Meade P, Strohmeier S, Brent RI, Richey ST, Haile A, Yang YR, Klebert MK, Suessen T, Teefey S, Presti RM, Krammer F, Kleinstein SH, Ward AB, Ellebedy AH. Human germinal centres engage memory and naive B cells after influenza vaccination. Nature 2020, 586: 127-132. PMID: 32866963, PMCID: PMC7566073, DOI: 10.1038/s41586-020-2711-0.Peer-Reviewed Original ResearchConceptsB cell clonesInfluenza vaccinationGerminal center B cellsB cellsGerminal center reactionCell clonesLymph nodesMonoclonal antibodiesPre-existing memory B cellsGerminal center B cell responsesStrain-specific monoclonal antibodiesCenter reactionUltrasound-guided fine-needle aspirationMajor public health threatEarly plasmablast responsesInfluenza virus vaccinationSeasonal influenza vaccinationCross-reactive monoclonal antibodiesB cell responsesMemory B cellsB-cell originFine-needle aspirationNaive B cellsPublic health threatHuman germinal centreSingle-cell repertoire tracing identifies rituximab-resistant B cells during myasthenia gravis relapses
Jiang R, Fichtner ML, Hoehn KB, Pham MC, Stathopoulos P, Nowak RJ, Kleinstein SH, O'Connor KC. Single-cell repertoire tracing identifies rituximab-resistant B cells during myasthenia gravis relapses. JCI Insight 2020, 5 PMID: 32573488, PMCID: PMC7453893, DOI: 10.1172/jci.insight.136471.Peer-Reviewed Original ResearchConceptsMuscle-specific kinase myasthenia gravisMemory B cellsB cell subsetsAntibody-secreting cellsB cellsCell subsetsAutoantibody-producing B cellsB-cell depleting therapyCell-depleting therapyB cell clonesB cell survivalGene expression signaturesMyasthenia gravisAutoimmune disordersRelapseB cell samplesReceptor profilingCell clonesExpression signaturesRituximabTherapyCell survivalCellsTreatmentCell samples
2019
Cyclin E Overexpression in Human Mammary Epithelial Cells Promotes Epithelial Cancer-Specific Copy Number Alterations
Giraldez S, Tamayo P, Wineinger N, Kim W, Reed S. Cyclin E Overexpression in Human Mammary Epithelial Cells Promotes Epithelial Cancer-Specific Copy Number Alterations. IScience 2019, 19: 850-859. PMID: 31513970, PMCID: PMC6739637, DOI: 10.1016/j.isci.2019.08.043.Peer-Reviewed Original ResearchChromosomal copy number alterationsCopy number alterationsCyclin ECell cycle regulatory proteinsOverexpression of cyclin EChromosomal lociCyclin E overexpressionEpithelial cell clonesRegulatory proteinsReplication stressCell cycleAberrant mitosesS phaseEpithelial-like tumorsCyclinE overexpressionCell clonesClonesOncogenesisComputational approachReplicationPotential mechanismsChromosomal damageCellsLociPathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity
Ruff WE, Dehner C, Kim WJ, Pagovich O, Aguiar CL, Yu AT, Roth AS, Vieira SM, Kriegel C, Adeniyi O, Mulla MJ, Abrahams VM, Kwok WW, Nussinov R, Erkan D, Goodman AL, Kriegel MA. Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity. Cell Host & Microbe 2019, 26: 100-113.e8. PMID: 31227334, PMCID: PMC8194364, DOI: 10.1016/j.chom.2019.05.003.Peer-Reviewed Original ResearchConceptsAntiphospholipid syndromePathogenic monoclonal antibodyHuman autoimmune diseasesGut commensalsB-cell autoepitopesHuman gut commensalGPI IgGAPS patientsIgG titersOral gavageMemory TSusceptible miceAntigenic loadAutoimmune diseasesAutoimmune pathologyTrigger autoimmunityHuman autoimmunityGlycoprotein IGPI autoantibodiesAutoimmunityMonoclonal antibodiesCell clonesCross reactMimotopesAutoantibodiesIsolation of gene-edited cells via knock-in of short glycophosphatidylinositol-anchored epitope tags
Zotova A, Pichugin A, Atemasova A, Knyazhanskaya E, Lopatukhina E, Mitkin N, Holmuhamedov E, Gottikh M, Kuprash D, Filatov A, Mazurov D. Isolation of gene-edited cells via knock-in of short glycophosphatidylinositol-anchored epitope tags. Scientific Reports 2019, 9: 3132. PMID: 30816313, PMCID: PMC6395743, DOI: 10.1038/s41598-019-40219-z.Peer-Reviewed Original ResearchConceptsEpitope tagKnock-inDonor DNA constructsTag-specific antibodiesTarget lociProtein tagsTarget promotersGene-edited cellsMammalian cellsGenome modificationSecreted proteinsChimeric proteinIsolation of cellsPlasma membraneTarget genesExpression cassetteDNA constructsCell clonesFACS sortingProteinGenesCassetteTransgene integrationIsolatesTags
2018
Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus
Greiling TM, Dehner C, Chen X, Hughes K, Iñiguez AJ, Boccitto M, Ruiz DZ, Renfroe SC, Vieira SM, Ruff WE, Sim S, Kriegel C, Glanternik J, Chen X, Girardi M, Degnan P, Costenbader KH, Goodman AL, Wolin SL, Kriegel MA. Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Science Translational Medicine 2018, 10 PMID: 29593104, PMCID: PMC5918293, DOI: 10.1126/scitranslmed.aan2306.Peer-Reviewed Original ResearchConceptsLupus patientsGlomerular immune complex depositsPositive lupus patientsImmune complex depositsGerm-free miceSigns of autoimmunityB cell responsesT cell clonesNovel treatment approachesTriggers of autoimmunityCommensal bacterial speciesEarliest autoantibodiesChronic autoimmunityAutoimmune diseasesHealthy controlsT cellsTreatment approachesSusceptible individualsAutoimmunityCell responsesCommensal speciesLupusPatientsCell clonesGut commensalsB Cell Presentation of Chlamydia Antigen Selects Out Protective CD4γ13 T Cells: Implications for Genital Tract Tissue-Resident Memory Lymphocyte Clusters
Johnson RM, Yu H, Strank N, Karunakaran K, Zhu Y, Brunham RC. B Cell Presentation of Chlamydia Antigen Selects Out Protective CD4γ13 T Cells: Implications for Genital Tract Tissue-Resident Memory Lymphocyte Clusters. Infection And Immunity 2018, 86: 10.1128/iai.00614-17. PMID: 29158429, PMCID: PMC5778355, DOI: 10.1128/iai.00614-17.Peer-Reviewed Original ResearchConceptsMemory lymphocyte clustersPeripheral blood mononuclear cellsT cell subsetsAntigen-presenting cellsT cell clonesB cell populationsT cellsLymphocyte clustersCell subsetsB cellsTissue-resident memory T cellsCD4 T-cell clonesCD4 T cell subsetsHuman peripheral blood mononuclear cellsCell clonesMemory T cellsBlood mononuclear cellsIL-13 responsesImmune B cellsB cell presentationCell populationsAdoptive transferImmune miceIntracellular bacterial pathogenChlamydia antigen
2017
Commensal Ro60 Orthologs as Persistent Triggers of Human Lupus
Dehner C, Greiling T, Chen X, Renfroe S, Hughes K, Vieira S, Ruff W, Boccitto M, Sim S, Chen X, Kriegel C, Degnan P, Goodman A, Wolin S, Kriegel M. Commensal Ro60 Orthologs as Persistent Triggers of Human Lupus. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.55.3.Peer-Reviewed Original ResearchMesenteric lymph nodesSystemic lupus erythematosusT cell clonesLupus patientsSLE patientsTg miceAutoimmune diseasesMicrobial triggersCell clonesT cellsGerm-free (GF) C57BL/6 miceP. propionicumMemory CD4 T cellsHuman SLE seraPrototypical autoimmune diseaseCD4 T cellsHuman autoimmune diseasesGerm-free miceAnti-Ro60 antibodiesEarliest autoantibodiesRo60 antibodiesLupus modelsLupus erythematosusLymph nodesHuman lupus
2015
Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia
Shojaee S, Caeser R, Buchner M, Park E, Swaminathan S, Hurtz C, Geng H, Chan LN, Klemm L, Hofmann WK, Qiu YH, Zhang N, Coombes KR, Paietta E, Molkentin J, Koeffler HP, Willman CL, Hunger SP, Melnick A, Kornblau SM, Müschen M. Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia. Cancer Cell 2015, 28: 114-128. PMID: 26073130, PMCID: PMC4565502, DOI: 10.1016/j.ccell.2015.05.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Transformation, NeoplasticDNA-Binding ProteinsDual Specificity Phosphatase 6Host Cell Factor C1HumansIntracellular Signaling Peptides and ProteinsMAP Kinase Signaling SystemMembrane ProteinsMiceMice, TransgenicMolecular Sequence DataPrecursor Cell Lymphoblastic Leukemia-LymphomaPrognosisProtein Serine-Threonine KinasesSmall Molecule LibrariesTranscription FactorsConceptsAcute lymphoblastic leukemiaLymphoblastic leukemiaPatient-derived preNegative feedback regulationPre-B cell cloneCell deathImmediate cell deathMouse modelSmall molecule inhibitorsTherapeutic targetAcute activationMalignant transformationCell clonesFeedback regulationOncogenic signalingMolecule inhibitorsStrong activationLeukemiaDeathERKPre-B-cell transformationCell transformationActivationOncogenic transformationVast majorityThymic Selection: To Thine Own Self Be True
Kitz A, Hafler DA. Thymic Selection: To Thine Own Self Be True. Immunity 2015, 42: 788-789. PMID: 25992854, DOI: 10.1016/j.immuni.2015.05.007.Peer-Reviewed Original ResearchDecoding astrocyte heterogeneity: New tools for clonal analysis
Bribián A, Figueres-Oñate M, Martín-López E, López-Mascaraque L. Decoding astrocyte heterogeneity: New tools for clonal analysis. Neuroscience 2015, 323: 10-19. PMID: 25917835, DOI: 10.1016/j.neuroscience.2015.04.036.Peer-Reviewed Original ResearchConceptsEmbryonic developmentAstrocyte lineagePowerful genetic toolsBiology of astrocytesGenetic toolsCell heterogeneityLineagesOntogenetic originAstrocyte heterogeneityClonal analysisPhysiological featuresSpecific labelingAstrocyte progenitorsClonesAdult brainCell clonesAstrocyte clonesFinal fateExciting areaNew toolProgenyBiologyProgenitors
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