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
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 cancer
2019
Lung 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 programsCD44Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2‐mediated signalling
Nguyen MB, Valdes VJ, Cohen I, Pothula V, Zhao D, Zheng D, Ezhkova E. Dissection of Merkel cell formation in hairy and glabrous skin reveals a common requirement for FGFR2‐mediated signalling. Experimental Dermatology 2019, 28: 374-382. PMID: 30758073, PMCID: PMC6488392, DOI: 10.1111/exd.13901.Peer-Reviewed Original ResearchConceptsCell formationCommon genetic programPaw skinMerkel cellsLineage-tracing experimentsBack skinTranscriptome studiesMerkel cell developmentGenetic programMAPK signalingPrimary hair folliclesCell developmentSpecialized structuresMechanosensory cellsSimilar regulatorsUpstream factorsCritical functionsPrecursor cellsFGFR2SignalingCellsTouch domesGlabrous skinMurineHair follicles
2017
Transcriptome 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
Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development
Perdigoto CN, Dauber KL, Bar C, Tsai PC, Valdes VJ, Cohen I, Santoriello FJ, Zhao D, Zheng D, Hsu YC, Ezhkova E. Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development. PLOS Genetics 2016, 12: e1006151. PMID: 27414999, PMCID: PMC4944976, DOI: 10.1371/journal.pgen.1006151.Peer-Reviewed Original ResearchConceptsMerkel cell specificationCell specificationPrimary hair folliclesLoss of PolycombImportance of ShhCell differentiation programHair follicle functionSonic hedgehog (Shh) signalingPRC2 targetsSpecialized keratinocytesEpidermal progenitorsDevelopmental programHair folliclesEpigenetic processesDifferentiation programHedgehog signalingShh ligandMature Merkel cellsShh signalingSkin developmentMurine dorsal skinEpidermal cellsMerkel cellsPRC2 lossCell formation
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