2024
Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity
Zhang T, Yu W, Cheng X, Yeung J, Ahumada V, Norris P, Pearson M, Yang X, van Deursen W, Halcovich C, Nassar A, Vesely M, Zhang Y, Zhang J, Ji L, Flies D, Liu L, Langermann S, LaRochelle W, Humphrey R, Zhao D, Zhang Q, Zhang J, Gu R, Schalper K, Sanmamed M, Chen L. Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity. Science Immunology 2024, 9: eadh2334. PMID: 38669316, DOI: 10.1126/sciimmunol.adh2334.Peer-Reviewed Original ResearchConceptsT cell infiltrationT cell exclusionT cellsResistance to anti-PD-1 immunotherapyPoor T-cell infiltrationAnti-PD-1 immunotherapyImmunogenic mouse tumorsT cell mobilizationHuman cancer tissuesTherapeutic immunotherapyCancer immunotherapyMouse tumorsChemokine systemImmunotherapyTumor tissuesImpaired infiltrationTumorLipid metabolitesHuman cancersCancer tissuesInfiltrationA2 groupCancerPLA2G10Up-regulated
2023
Transcriptomic identification of genes expressed in invasive S. aureus diabetic foot ulcer infection
Agidigbi T, Kwon H, Knight J, Zhao D, Lee F, Oh I. Transcriptomic identification of genes expressed in invasive S. aureus diabetic foot ulcer infection. Frontiers In Cellular And Infection Microbiology 2023, 13: 1198115. PMID: 37434783, PMCID: PMC10332306, DOI: 10.3389/fcimb.2023.1198115.Peer-Reviewed Original ResearchConceptsDiabetic foot ulcersPeripheral blood mononuclear cellsHost immune responseActive infectionImmune responseDiabetic foot ulcer infectionsInfected diabetic foot ulcersFoot ulcer infectionsPatients 8 weeksIntravenous antibiotic therapyBlood mononuclear cellsWound healing statusDFU infectionsPBMC expressionSalvage therapyUlcer infectionDifferent time pointsAntibiotic therapyMajor complicationsSurgical treatmentFoot ulcersMononuclear cellsPotential intervention optionsSpecies-specific infectionTreatment responseNasal host response-based screening for undiagnosed respiratory viruses: a pathogen surveillance and detection study
Cheemarla N, Hanron A, Fauver J, Bishai J, Watkins T, Brito A, Zhao D, Alpert T, Vogels C, Ko A, Schulz W, Landry M, Grubaugh N, van Dijk D, Foxman E. Nasal host response-based screening for undiagnosed respiratory viruses: a pathogen surveillance and detection study. The Lancet Microbe 2023, 4: e38-e46. PMID: 36586415, PMCID: PMC9835789, DOI: 10.1016/s2666-5247(22)00296-8.Peer-Reviewed Original ResearchConceptsRespiratory virus panelPg/mLCXCL10 concentrationsSARS-CoV-2Bacterial pathobiontsRespiratory virusesSARS-CoV-2 negative samplesViral respiratory infectionsSARS-CoV-2 positive samplesClinical virology laboratoryHealth care systemVirus-positive samplesQuantitative RT-PCRInfluenza C virusSymptomatic patientsRespiratory infectionsSeasonal coronavirusesNasopharyngeal swabsVirus panelC virusCommon virusesCXCL10Host responseInterferon responseVirology laboratory
2022
RASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition.
Hunihan L, Zhao D, Lazowski H, Li M, Qian Y, Abriola L, Surovtseva YV, Muthusamy V, Tanoue LT, Rothberg BE, Schalper KA, Herbst RS, Wilson FH. RASGRF1 Fusions Activate Oncogenic RAS Signaling and Confer Sensitivity to MEK Inhibition. Clinical Cancer Research 2022, 28: 3091-3103. PMID: 35247929, PMCID: PMC9288503, DOI: 10.1158/1078-0432.ccr-21-4291.Peer-Reviewed Original ResearchConceptsLung adenocarcinomaSmoking historyPack-year smoking historyMinimal smoking historySubset of patientsPancreatic ductal adenocarcinoma cell linesPotential treatment strategyTight junction protein occludinJunction protein occludinWhole-exome sequencingAdenocarcinoma cell lineAdvanced malignanciesCancer Genome AtlasRaf-MEKAdvanced tumorsMultiple malignanciesTreatment strategiesKRAS mutationsTherapeutic strategiesTherapeutic targetOncogenic RAS SignalingRelated commentaryOncogenic driversMEK inhibitionOncogenic alterationsFunctional Analysis of MET Exon 14 Skipping Alteration in Cancer Invasion and Metastatic DisseminationMET Exon 14 Skipping Alteration Promotes Metastasis
Wang F, Liu Y, Qiu W, Shum E, Feng M, Zhao D, Zheng D, Borczuk A, Cheng H, Halmos B. Functional Analysis of MET Exon 14 Skipping Alteration in Cancer Invasion and Metastatic DisseminationMET Exon 14 Skipping Alteration Promotes Metastasis. Cancer Research 2022, 82: 1365-1379. PMID: 35078819, DOI: 10.1158/0008-5472.can-21-1327.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerMetastasis in vivoLung cancerInvasive capacity in vitroExtracellular matrix disassemblyReceptor kinase activityTumor progression of non-small cell lung cancerRNA sequencing analysisImpaired receptor internalizationTreatment of lung cancerMetastasis-related pathwaysCell lung cancerMolecular mechanisms of actionCytoskeleton remodelingEndocytic degradationSequence analysisCell scatteringEffective treatment of lung cancerPotential therapeutic optionCRISPR editingCell movementKinase activityMechanistic functionProgression of non-small cell lung cancerMatrix disassembly
2021
CIDEA expression in SAT from adolescent girls with obesity and unfavorable patterns of abdominal fat distribution
Tarabra E, Nouws J, Vash‐Margita A, Hellerstein M, Shabanova V, McCollum S, Pierpont B, Zhao D, Shulman GI, Caprio S. CIDEA expression in SAT from adolescent girls with obesity and unfavorable patterns of abdominal fat distribution. Obesity 2021, 29: 2068-2080. PMID: 34672413, PMCID: PMC8612981, DOI: 10.1002/oby.23295.Peer-Reviewed Original ResearchConceptsAbdominal fat distributionVisceral adipose tissueCIDEA expressionFat distributionProtein levelsAbdominal SATAdolescent girlsHigher visceral adipose tissueSubcutaneous adipose tissue biopsiesAdipose tissue biopsiesReverse transcription-polymerase chain reactionTranscription-polymerase chain reactionMagnetic resonance imagingWeight gain effectsExpression of CIDEAAdipocyte dysfunctionSAT biopsiesAdipose lipidsInsulin resistanceAdipocyte hypertrophySmall adipocytesAdipose tissueTissue biopsiesUnfavorable patternsStrong inverse correlationDynamic 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 replicationA Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Sanmamed MF, Nie X, Desai SS, Villaroel-Espindola F, Badri T, Zhao D, Kim AW, Ji L, Zhang T, Quinlan E, Cheng X, Han X, Vesely MD, Nassar AF, Sun J, Zhang Y, Kim TK, Wang J, Melero I, Herbst RS, Schalper KA, Chen L. A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy. Cancer Discovery 2021, 11: 1700-1715. PMID: 33658301, PMCID: PMC9421941, DOI: 10.1158/2159-8290.cd-20-0962.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesExhausted T cellsTIL subsetsTumor microenvironmentCancer immunotherapyT cellsAdvanced non-small cell lung cancerPatient-derived tumor xenograft modelAnti-PD therapyT cell subsetsCell lung cancerPotential tissue biomarkersBaseline tumor tissueLung cancer tissuesSingle-cell mass cytometryTumor xenograft modelApoptotic CD8Dysfunctional CD8Immunotherapy resistancePD-1Activation markersAdjacent nontumoral tissuesPathway-dependent mannerLung cancerPolycomb complexes redundantly maintain epidermal stem cell identity during development
Cohen I, Bar C, Liu H, Valdes VJ, Zhao D, Galbo PM, Silva JM, Koseki H, Zheng D, Ezhkova E. Polycomb complexes redundantly maintain epidermal stem cell identity during development. Genes & Development 2021, 35: 354-366. PMID: 33602871, PMCID: PMC7919412, DOI: 10.1101/gad.345363.120.Peer-Reviewed Original ResearchConceptsFunctional redundancyTranscription factorsRepressive chromatin domainsStem cell identityEpidermal stem cellsStrong derepressionEpidermal identityPolycomb complexesChromatin domainsDevelopmental regulatorsIdentity genesPRC2 functionGene repressionGenomic bindingCell identityMolecular dissectionEpidermal progenitorsLineage identityPRC2PRC1Ectopic expressionSevere defectsEpidermal stratificationPhysiological significanceStem cellsMulti-omics analysis to identify susceptibility genes for colorectal cancer
Yuan Y, Bao J, Chen Z, Villanueva A, Wen W, Wang F, Zhao D, Fu X, Cai Q, Long J, Shu X, Zheng D, Moreno V, Zheng W, Lin W, Guo X. Multi-omics analysis to identify susceptibility genes for colorectal cancer. Human Molecular Genetics 2021, 30: 321-330. PMID: 33481017, PMCID: PMC8485221, DOI: 10.1093/hmg/ddab021.Peer-Reviewed Original ResearchMeSH KeywordsCarcinogenesisCell Line, TumorCell ProliferationColorectal NeoplasmsDNA MethylationGene Expression Regulation, NeoplasticGenetic Association StudiesGenetic Predisposition to DiseaseGenomeGenome-Wide Association StudyHumansNerve Tissue ProteinsPolymorphism, Single NucleotideRepressor ProteinsRisk FactorsTranscriptomeConceptsGenome-wide association studiesMulti-omics analysisSusceptibility genesTarget genesPutative target genesGWAS-identified variantsMost genetic variantsDNA methylation dataNovel susceptibility genesGenotype-Tissue ExpressionGenetic risk lociPutative susceptibility genesGene regulationIntergenic regionPathogenic dysregulationCancer Genome AtlasEpithelial-mesenchymal transitionRisk lociGene expressionMethylation dataAssociation studiesGenesCell behaviorGenetic variantsGenome Atlas
2019
Genomic sites hypersensitive to ultraviolet radiation
Premi S, Han L, Mehta S, Knight J, Zhao D, Palmatier MA, Kornacker K, Brash DE. Genomic sites hypersensitive to ultraviolet radiation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 24196-24205. PMID: 31723047, PMCID: PMC6883822, DOI: 10.1073/pnas.1907860116.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated RegionsCells, CulturedDNA DamageFibroblastsGene Expression RegulationGenome, HumanHigh-Throughput Nucleotide SequencingHumansMelanocytesMelanomaMutationPromoter Regions, GeneticProtein BiosynthesisPyrimidine DimersPyrimidine NucleotidesSkin NeoplasmsTOR Serine-Threonine KinasesUltraviolet RaysConceptsCyclobutane pyrimidine dimersETS family transcription factorsIndividual gene promotersFamily transcription factorsRNA-binding proteinPrimary human melanocytesSingle-base resolutionEpigenetic marksGenomic averageTranslation regulationGenomic sitesMotif locationsTranscription factorsCell physiologyGene promoterCancer driversGenomeHuman melanocytesCell typesTumor evolutionCell pathwaysRare mutationsUV targetPyrimidine dimersApurinic sitesLung Mammary Metastases but Not Primary Tumors Induce Accumulation of Atypical Large Platelets and Their Chemokine Expression
Zheng W, Zhang H, Zhao D, Zhang J, Pollard JW. Lung Mammary Metastases but Not Primary Tumors Induce Accumulation of Atypical Large Platelets and Their Chemokine Expression. Cell Reports 2019, 29: 1747-1755.e4. PMID: 31722193, PMCID: PMC6919330, DOI: 10.1016/j.celrep.2019.10.016.Peer-Reviewed Original ResearchConceptsTumor microenvironmentLung metastasesEndothelial cellsLarge plateletsPrimary mammary tumorsEndothelial progenitor cellsConsiderable cellular heterogeneityMammary cancer metastasisAuthentic endothelial cellsMammary metastasesMetastatic sitesChemokine expressionMammary tumorsMetastatic growthMetastasisTherapeutic interventionsCellular playersCD44 upregulationCancer metastasisProgenitor cellsPlateletsInduces accumulationIndirect mechanismsDistinct gene expression programsCD44
2018
SMARTcleaner: identify and clean off-target signals in SMART ChIP-seq analysis
Zhao D, Zheng D. SMARTcleaner: identify and clean off-target signals in SMART ChIP-seq analysis. BMC Bioinformatics 2018, 19: 544. PMID: 30587107, PMCID: PMC6307164, DOI: 10.1186/s12859-018-2577-4.Peer-Reviewed Original ResearchEnriched expression of genes associated with autism spectrum disorders in human inhibitory neurons
Wang P, Zhao D, Lachman HM, Zheng D. Enriched expression of genes associated with autism spectrum disorders in human inhibitory neurons. Translational Psychiatry 2018, 8: 13. PMID: 29317598, PMCID: PMC5802446, DOI: 10.1038/s41398-017-0058-6.Peer-Reviewed Original ResearchConceptsASD candidatesEnriched expressionSingle-cell transcriptomic dataSingle-cell transcriptome profilesCo-expression gene modulesDifferent developmental stagesExcitatory/inhibitory (E/I) imbalance hypothesisInhibitory neuronsGene networksTranscriptome profilesGene modulesTranscriptomic dataUpregulated genesDownstream targetsGene expressionDevelopmental stagesCell typesGenesNeuron subtypesFunctional evidenceAutism spectrum disorderExpressionASD brainCortex samplesExcitatory neurons
2017
Characteristics of allelic gene expression in human brain cells from single-cell RNA-seq data analysis
Zhao D, Lin M, Pedrosa E, Lachman HM, Zheng D. Characteristics of allelic gene expression in human brain cells from single-cell RNA-seq data analysis. BMC Genomics 2017, 18: 860. PMID: 29126398, PMCID: PMC5681780, DOI: 10.1186/s12864-017-4261-x.Peer-Reviewed Original ResearchConceptsMonoallelic expressionHuman brain cellsGene expressionMonoallelic gene expressionAllelic gene expressionGenome-wide levelSingle-cell RNA-seq datasetsRNA-seq data analysisAllelic expression studiesSingle-cell RNA-seq data analysisRNA-seq datasetsSingle nucleotide variantsBrain cellsCellular identityAutosomal genesNeuronal diversityExpression studiesNucleotide variantsCorrelated expressionGenesIndividual cellsHuman psychiatric disordersNeuronal cellsSingle cellsCell functionTranscriptome analysis of microglia in a mouse model of Rett syndrome: differential expression of genes associated with microglia/macrophage activation and cellular stress
Zhao D, Mokhtari R, Pedrosa E, Birnbaum R, Zheng D, Lachman HM. Transcriptome analysis of microglia in a mouse model of Rett syndrome: differential expression of genes associated with microglia/macrophage activation and cellular stress. Molecular Autism 2017, 8: 17. PMID: 28367307, PMCID: PMC5372344, DOI: 10.1186/s13229-017-0134-z.Peer-Reviewed Original ResearchConceptsHeat shock protein familyShock protein familyWhole transcriptome analysisChromatin regulatorsAnalysis of microgliaPhenotypic phasesTranscriptome analysisProtein familyRNA-seqCellular stressMethyl-CpGRTT phenotypeRTT pathogenesisDe novo lossGene expressionM2 activation statesFemale miceDifferential expressionFunction mutationsHSP pathwayGenesMolecular pathwaysCell typesExtracellular matrixProtein 2
2016
Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks
Nebel RA, Zhao D, Pedrosa E, Kirschen J, Lachman HM, Zheng D, Abrahams BS. Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks. PLOS ONE 2016, 11: e0148039. PMID: 26824476, PMCID: PMC4732616, DOI: 10.1371/journal.pone.0148039.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultBase SequenceChromosomes, Human, Pair 15EpilepsyGene Expression ProfilingGene Expression RegulationGene Knockdown TechniquesGene Regulatory NetworksGenetic LociHeterozygoteHumansMaleMiddle AgedMolecular Sequence DataNerve Tissue ProteinsNeural Stem CellsPrimary Cell CultureRiskSchizophreniaSequence DeletionConceptsEpilepsy genesRole of CYFIP1Novel disease candidatesHuman neural progenitorsEpilepsy riskSubset of DEGsPostsynaptic density genesNeuronal differentiationFMRP targetsGene networksNeural progenitorsSchizophreniaCytoskeletal remodelingRNA-seqDeletion carriersKnockdown experimentsVariable expressivityDisease genesProgenitors resultsDisease candidatesGenesCellular assaysCYFIP1DisordersDysregulation
2015
MicroRNA Profiling of Neurons Generated Using Induced Pluripotent Stem Cells Derived from Patients with Schizophrenia and Schizoaffective Disorder, and 22q11.2 Del
Zhao D, Lin M, Chen J, Pedrosa E, Hrabovsky A, Fourcade HM, Zheng D, Lachman HM. MicroRNA Profiling of Neurons Generated Using Induced Pluripotent Stem Cells Derived from Patients with Schizophrenia and Schizoaffective Disorder, and 22q11.2 Del. PLOS ONE 2015, 10: e0132387. PMID: 26173148, PMCID: PMC4501820, DOI: 10.1371/journal.pone.0132387.Peer-Reviewed Original ResearchConceptsGenome-wide significanceUnderlying genetic basisInduced pluripotent stem cellsPluripotent stem cell (iPSC) technologyMiRNA expression profilingPluripotent stem cellsMiRNA expression patternsMicroRNA biogenesisMRNA targetsRegulated miRNAsGenetic basisExpression profilingStem cell technologyExpression patternsAutopsy samplesMiRNAsNeuropsychiatric disordersMicroRNA profilingStem cellsNominal significanceGenesPeripheral cellsPeripheral bloodWider significanceGenetic factors
2014
Heat Shock Alters the Expression of Schizophrenia and Autism Candidate Genes in an Induced Pluripotent Stem Cell Model of the Human Telencephalon
Lin M, Zhao D, Hrabovsky A, Pedrosa E, Zheng D, Lachman HM. Heat Shock Alters the Expression of Schizophrenia and Autism Candidate Genes in an Induced Pluripotent Stem Cell Model of the Human Telencephalon. PLOS ONE 2014, 9: e94968. PMID: 24736721, PMCID: PMC3988108, DOI: 10.1371/journal.pone.0094968.Peer-Reviewed Original ResearchConceptsCopy number variantsCandidate genesHS-inducible genesMaternal immune activationPluripotent stem cell modelsCellular stress pathwaysInduced Pluripotent Stem Cell ModelDisease-causing genetic variantsHeritable neuropsychiatric disorderStem cell modelAutism candidate genesPluripotent stem cellsCommon environmental stressorsCellular stressorsGenes decreasesRNA-seqASD candidatesASD genesHeat shockCopy lossHuman brain developmentEnvironmental stressorsHeat shock altersGenesStress pathways