2022
Nicotine dose-dependent epigenomic-wide DNA methylation changes in the mice with long-term electronic cigarette exposure.
Peng G, Xi Y, Bellini C, Pham K, Zhuang ZW, Yan Q, Jia M, Wang G, Lu L, Tang MS, Zhao H, Wang H. Nicotine dose-dependent epigenomic-wide DNA methylation changes in the mice with long-term electronic cigarette exposure. American Journal Of Cancer Research 2022, 12: 3679-3692. PMID: 36119846, PMCID: PMC9442002.Peer-Reviewed Original ResearchElectronic cigarette exposureCigarette exposureMale ApoE-/- miceApoE-/- miceCytokine mRNA expressionPoor health outcomesWhite blood cellsElectronic cigarette useDose-dependent mannerE-cigarette aerosolAerosol inhalationCigarette smokingActivation of MAPKHigher nicotine concentrationsMAPK pathway activationCell-damaging effectsCpG sitesHealth outcomesCigarette useMRNA expressionNicotine concentrationsPathway activationSignificant CpG sitesBlood cellsSignificant alterationsHIV viral transcription and immune perturbations in the CNS of people with HIV despite ART
Farhadian SF, Lindenbaum O, Zhao J, Corley MJ, Im Y, Walsh H, Vecchio A, Garcia-Milian R, Chiarella J, Chintanaphol M, Calvi R, Wang G, Ndhlovu LC, Yoon J, Trotta D, Ma S, Kluger Y, Spudich S. HIV viral transcription and immune perturbations in the CNS of people with HIV despite ART. JCI Insight 2022, 7: e160267. PMID: 35801589, PMCID: PMC9310520, DOI: 10.1172/jci.insight.160267.Peer-Reviewed Original ResearchConceptsCerebrospinal fluidHIV infectionHIV-1-infected cellsCNS viral persistenceCentral memory CD4T-cell abnormalitiesHIV-1 RNAMicroglia-like cellsT cell activationSystemic viral suppressionAbnormal CD8HIV neuropathogenesisViral suppressionMemory CD4CNS reservoirsImmune perturbationsExperience elevated ratesNeuroimmune effectsPeripheral bloodNeurological impairmentViral persistenceT cellsCell abnormalitiesUninfected controlsCell activationMonospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617
Peng L, Hu Y, Mankowski MC, Ren P, Chen RE, Wei J, Zhao M, Li T, Tripler T, Ye L, Chow RD, Fang Z, Wu C, Dong MB, Cook M, Wang G, Clark P, Nelson B, Klein D, Sutton R, Diamond MS, Wilen CB, Xiong Y, Chen S. Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617. Nature Communications 2022, 13: 1638. PMID: 35347138, PMCID: PMC8960874, DOI: 10.1038/s41467-022-29288-3.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Authentic SARS-CoV-2Effective therapeutic optionPotent SARS-CoV-2SARS-CoV-2 variantsVariants of concernRepertoire of therapeuticsBreakthrough infectionsTherapeutic optionsMultiple vaccinesPathogen SARS-CoV-2Delta variantB cellsPotent efficacyHumanized antibodyDistinct epitopesBispecific antibodiesOriginal virusSpike receptorStrong inhibitory activityMonoclonal antibodiesAntibodiesStrong potencyLead clonesLead antibodiesSingle-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
2021
Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics
Cheemarla NR, Watkins TA, Mihaylova VT, Wang B, Zhao D, Wang G, Landry ML, Foxman EF. Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics. Journal Of Experimental Medicine 2021, 218: e20210583. PMID: 34128960, PMCID: PMC8210587, DOI: 10.1084/jem.20210583.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAngiotensin-Converting Enzyme 2Case-Control StudiesChemokine CXCL10COVID-19Disease SusceptibilityFemaleGene Expression ProfilingHost-Pathogen InteractionsHumansImmunity, InnateInterferonsMaleMiddle AgedNasopharynxPicornaviridae InfectionsSARS-CoV-2Viral LoadVirus ReplicationConceptsSARS-CoV-2 infectionSARS-CoV-2 exposureSARS-CoV-2Interferon-stimulated genesUpper respiratory tractRespiratory tractEarly SARS-CoV-2 infectionDynamic innate immune responseViral replicationSARS-CoV-2 replicationPatient nasopharyngeal samplesInnate immune responseLow infectious doseViral loadNasopharyngeal samplesImmune responseInfectious doseISG responseAntiviral responseInfection progressionViral transmissionLevel correlatesInfectionISG inductionInitial replicationSingle-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replicationNeuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2020
A single-cell analysis of the molecular lineage of chordate embryogenesis
Zhang T, Xu Y, Imai K, Fei T, Wang G, Dong B, Yu T, Satou Y, Shi W, Bao Z. A single-cell analysis of the molecular lineage of chordate embryogenesis. Science Advances 2020, 6: eabc4773. PMID: 33148647, PMCID: PMC7673699, DOI: 10.1126/sciadv.abc4773.Peer-Reviewed Original ResearchConceptsCell typesEmbryonic cell lineagesSingle-cell RNA sequencing analysisAsymmetric cell divisionWild-type embryosCell lineage differentiationMouse cell typesOnset of gastrulationSingle-cell datasetsRNA sequencing analysisSingle-cell analysisMolecular lineagesFate transformationChordate embryogenesisEarly embryogenesisConvergent differentiationMother cellsNotochord lineageCell divisionTranscription factorsLineage developmentMaster regulatorLineage differentiationGene pathwaysCell lineagesSmooth Muscle Cell Reprogramming in Aortic Aneurysms
Chen PY, Qin L, Li G, Malagon-Lopez J, Wang Z, Bergaya S, Gujja S, Caulk AW, Murtada SI, Zhang X, Zhuang ZW, Rao DA, Wang G, Tobiasova Z, Jiang B, Montgomery RR, Sun L, Sun H, Fisher EA, Gulcher JR, Fernandez-Hernando C, Humphrey JD, Tellides G, Chittenden TW, Simons M. Smooth Muscle Cell Reprogramming in Aortic Aneurysms. Cell Stem Cell 2020, 26: 542-557.e11. PMID: 32243809, PMCID: PMC7182079, DOI: 10.1016/j.stem.2020.02.013.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsAortic aneurysmAneurysm developmentMedial smooth muscle cellsAortic aneurysm developmentContractile smooth muscle cellsGrowth factor βHypercholesterolemic dietSmooth muscleAortic wallMesenchymal stem cellsMuscle cellsAneurysmsMarked increaseFactor βExuberant growthStem cellsHuman diseasesCell massCellsAtherosclerosisHypercholesterolemiaInflammationAortaApoEChronic mTOR activation induces a degradative smooth muscle cell phenotype
Li G, Wang M, Caulk AW, Cilfone NA, Gujja S, Qin L, Chen PY, Chen Z, Yousef S, Jiao Y, He C, Jiang B, Korneva A, Bersi MR, Wang G, Liu X, Mehta S, Geirsson A, Gulcher JR, Chittenden TW, Simons M, Humphrey JD, Tellides G. Chronic mTOR activation induces a degradative smooth muscle cell phenotype. Journal Of Clinical Investigation 2020, 130: 1233-1251. PMID: 32039915, PMCID: PMC7269581, DOI: 10.1172/jci131048.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic Aneurysm, ThoracicAortic DissectionBeta CateninDisease Models, AnimalLysosomesMechanistic Target of Rapamycin Complex 1MiceMice, Knockout, ApoEMicrophthalmia-Associated Transcription FactorMyocytes, Smooth MuscleSignal TransductionTOR Serine-Threonine KinasesTuberous Sclerosis Complex 1 ProteinConceptsMTOR activationMTOR complex 1Smooth muscle cell phenotypeMuscle cell phenotypeContext of hyperlipidemiaSmooth muscle cell proliferationThoracic aortic aneurysmDegradative organellesMuscle cell proliferationHematopoietic lineage markersSMC phenotypeLysosomal clearanceAdvanced diseaseMedial degenerationAortic diseaseLysosomal markersAortic aneurysmExtracellular matrixPhenotypic modulationConventional macrophagesMacrophage markersMedial SMCsConditional disruptionLineage markersImmune effectors
2016
The time-resolved transcriptome of C. elegans
Boeck ME, Huynh C, Gevirtzman L, Thompson OA, Wang G, Kasper DM, Reinke V, Hillier LW, Waterston RH. The time-resolved transcriptome of C. elegans. Genome Research 2016, 26: 1441-1450. PMID: 27531719, PMCID: PMC5052054, DOI: 10.1101/gr.202663.115.Peer-Reviewed Original ResearchConceptsTime-resolved transcriptomeAlternative splice formsPost-embryonic stagesRNA-seq dataLife cycleC. elegansNematode CaenorhabditisHistone mRNATranscriptional programsLate embryogenesisRNA-seqSplice formsPromoter usageSplice junctionsDifferential usageDetailed annotationGenesExpression correlatesCaenorhabditisElegansTranscriptomeOperonWormBaseEmbryogenesisSL1
2014
The C. elegans SNAPc Component SNPC-4 Coats piRNA Domains and Is Globally Required for piRNA Abundance
Kasper DM, Wang G, Gardner KE, Johnstone TG, Reinke V. The C. elegans SNAPc Component SNPC-4 Coats piRNA Domains and Is Globally Required for piRNA Abundance. Developmental Cell 2014, 31: 145-158. PMID: 25373775, PMCID: PMC4223638, DOI: 10.1016/j.devcel.2014.09.015.Peer-Reviewed Original ResearchConceptsRNA genesPIWI-interacting RNA (piRNA) pathwayTransfer RNA genesSmall RNA genesDiscrete genomic regionsDNA-binding subunitSmall nuclear RNAPiRNA abundanceRNA pathwaysPiRNA genesChromatin organizationPiRNA clustersPiRNA expressionProtein complexesGenomic regionsCoordinated expressionNuclear RNAExpression environmentForeign sequencesGenesExpressionDomainPiRNAsLocalizationTransposonComparative analysis of the transcriptome across distant species
Gerstein MB, Rozowsky J, Yan KK, Wang D, Cheng C, Brown JB, Davis CA, Hillier L, Sisu C, Li JJ, Pei B, Harmanci AO, Duff MO, Djebali S, Alexander RP, Alver BH, Auerbach R, Bell K, Bickel PJ, Boeck ME, Boley NP, Booth BW, Cherbas L, Cherbas P, Di C, Dobin A, Drenkow J, Ewing B, Fang G, Fastuca M, Feingold EA, Frankish A, Gao G, Good PJ, Guigó R, Hammonds A, Harrow J, Hoskins RA, Howald C, Hu L, Huang H, Hubbard TJ, Huynh C, Jha S, Kasper D, Kato M, Kaufman TC, Kitchen RR, Ladewig E, Lagarde J, Lai E, Leng J, Lu Z, MacCoss M, May G, McWhirter R, Merrihew G, Miller DM, Mortazavi A, Murad R, Oliver B, Olson S, Park PJ, Pazin MJ, Perrimon N, Pervouchine D, Reinke V, Reymond A, Robinson G, Samsonova A, Saunders GI, Schlesinger F, Sethi A, Slack FJ, Spencer WC, Stoiber MH, Strasbourger P, Tanzer A, Thompson OA, Wan KH, Wang G, Wang H, Watkins KL, Wen J, Wen K, Xue C, Yang L, Yip K, Zaleski C, Zhang Y, Zheng H, Brenner SE, Graveley BR, Celniker SE, Gingeras TR, Waterston R. Comparative analysis of the transcriptome across distant species. Nature 2014, 512: 445-448. PMID: 25164755, PMCID: PMC4155737, DOI: 10.1038/nature13424.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaenorhabditis elegansChromatinCluster AnalysisDrosophila melanogasterGene Expression ProfilingGene Expression Regulation, DevelopmentalHistonesHumansLarvaModels, GeneticMolecular Sequence AnnotationPromoter Regions, GeneticPupaRNA, UntranslatedSequence Analysis, RNATranscriptome
2013
Common PTP4A1‐PHF3‐EYS variants are specific for alcohol dependence
Zuo L, Wang K, Wang G, Pan X, Zhang X, Zhang H, Luo X. Common PTP4A1‐PHF3‐EYS variants are specific for alcohol dependence. American Journal On Addictions 2013, 23: 411-414. PMID: 24961364, PMCID: PMC4111256, DOI: 10.1111/j.1521-0391.2013.12115.x.Peer-Reviewed Original ResearchTissue-specific direct targets of Caenorhabditis elegans Rb/E2F dictate distinct somatic and germline programs
Kudron M, Niu W, Lu Z, Wang G, Gerstein M, Snyder M, Reinke V. Tissue-specific direct targets of Caenorhabditis elegans Rb/E2F dictate distinct somatic and germline programs. Genome Biology 2013, 14: r5. PMID: 23347407, PMCID: PMC4053757, DOI: 10.1186/gb-2013-14-1-r5.Peer-Reviewed Original ResearchConceptsRb/E2FLin-35Target genesGenome-wide binding profilesGene expressionTissue-specific gene regulationLin-35 mutantsDistinct cell fatesSmall RNA pathwaysEffector target genesDirect target geneBinding profileGermline programHPL-2Chromatin associationH3K36 methylationRNA pathwaysCSR-1Germline transformationC. elegansGene regulationCell fateE2FDirect targetMultiple tissues
2011
A Comprehensive Analysis of Gene Expression Changes Provoked by Bacterial and Fungal Infection in C. elegans
Engelmann I, Griffon A, Tichit L, Montañana-Sanchis F, Wang G, Reinke V, Waterston RH, Hillier LW, Ewbank JJ. A Comprehensive Analysis of Gene Expression Changes Provoked by Bacterial and Fungal Infection in C. elegans. PLOS ONE 2011, 6: e19055. PMID: 21602919, PMCID: PMC3094335, DOI: 10.1371/journal.pone.0019055.Peer-Reviewed Original ResearchConceptsC. elegansGenome-wide transcriptional changesFuture functional dissectionGene expression changesInnate immune signalingFunctional dissectionTranscriptional responseAnnotation analysisTranscriptional changesD. coniosporaRNA sequencingFungal pathogensCertain genesExpression changesImmune signalingSmall proteinsStress responseElegansGenesDistinct pathogensBacterial pathogensPathogensPhysiological imbalanceFungal infectionsHost response
2010
Prediction and characterization of noncoding RNAs in C. elegans by integrating conservation, secondary structure, and high-throughput sequencing and array data
Lu ZJ, Yip KY, Wang G, Shou C, Hillier LW, Khurana E, Agarwal A, Auerbach R, Rozowsky J, Cheng C, Kato M, Miller DM, Slack F, Snyder M, Waterston RH, Reinke V, Gerstein MB. Prediction and characterization of noncoding RNAs in C. elegans by integrating conservation, secondary structure, and high-throughput sequencing and array data. Genome Research 2010, 21: 276-285. PMID: 21177971, PMCID: PMC3032931, DOI: 10.1101/gr.110189.110.Peer-Reviewed Original ResearchConceptsNovel ncRNA candidatesNcRNA candidatesC. elegansC. elegans genomeWhole-genome identificationSpecific transcription factorsHigh-throughput sequencingDistinct expression patternsSecondary structure stabilityEvolutionary conservationGenomic elementsModENCODE consortiumNucleic acid levelIntergenic regionTranscription factorsPotential ncRNAsExpression patternsExpression dataDevelopmental stagesSecondary structureElegansNcRNAsRNAsStructural familyArray data
2008
A C. elegans Piwi, PRG-1, Regulates 21U-RNAs during Spermatogenesis
Wang G, Reinke V. A C. elegans Piwi, PRG-1, Regulates 21U-RNAs during Spermatogenesis. Current Biology 2008, 18: 861-867. PMID: 18501605, PMCID: PMC2494713, DOI: 10.1016/j.cub.2008.05.009.Peer-Reviewed Original ResearchConceptsPRG-1Small RNAsC. elegansGerm cellsSubset of mRNAsPRG 2Cell totipotencyPIWI proteinsP granulesRibonucleoprotein granulesEpigenetic regulationSpecific family membersGerm linePiwi familyProper expressionPiwiSuccessful spermatogenesisDiverse classPiRNAsRNAElegansProteinSpermatogenesisExpressionFamily members