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-regulatedAuto-sumoylation of the Ubc9 E2 SUMO-conjugating Enzyme Extends Cellular Lifespan.
Ryu HY, Jeong DW, Kim SY, Jeoung SW, Zhao D, Knight J, Lam T, Jin JH, Lee HS, Hochstrasser M. Auto-sumoylation of the Ubc9 E2 SUMO-conjugating Enzyme Extends Cellular Lifespan. Res Sq 2024 PMID: 38562857, DOI: 10.21203/rs.3.rs-4016606/v1.Peer-Reviewed Original ResearchASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts.
Hu B, Wiesehöfer M, de Miguel F, Liu Z, Chan L, Choi J, Melnick M, Arnal Estape A, Walther Z, Zhao D, Lopez-Giraldez F, Wurtz A, Cai G, Fan R, Gettinger S, Xiao A, Yan Q, Homer R, Nguyen D, Politi K. ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts. Cancer Research 2024, 84: 1303-1319. PMID: 38359163, PMCID: PMC11142404, DOI: 10.1158/0008-5472.can-23-0438.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsPatient-derived xenograftsEGFR mutant lung cancerMutant lung cancerPre-treatment tumorsResidual diseaseDrug toleranceLung cancerResidual tumor cells in vivoEGFR mutant lung adenocarcinomaTyrosine kinase inhibitor osimertinibEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitor treatmentTumor cells in vivoMutant lung adenocarcinomaMaximal tumor regressionTranscription factor Ascl1Drug-tolerant cellsTime of maximal responseEvidence of cellsCells in vivoOsimertinib treatmentTumor regressionSingle cell transcriptional profilingTumor cells
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 responseHigh-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways
Mendes H, Neelakantan U, Liu Y, Fitzpatrick S, Chen T, Wu W, Pruitt A, Jin D, Jamadagni P, Carlson M, Lacadie C, Enriquez K, Li N, Zhao D, Ijaz S, Sakai C, Szi C, Rooney B, Ghosh M, Nwabudike I, Gorodezky A, Chowdhury S, Zaheer M, McLaughlin S, Fernandez J, Wu J, Eilbott J, Vander Wyk B, Rihel J, Papademetris X, Wang Z, Hoffman E. High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways. Cell Reports 2023, 42: 112243. PMID: 36933215, PMCID: PMC10277173, DOI: 10.1016/j.celrep.2023.112243.Peer-Reviewed Original ResearchConceptsGene lossFunctional analysisHigh-throughput functional analysisZebrafish mutantsGene discoverySelect mutantsASD genesAutism genesKey pathwaysASD biologyBrain size differencesMutantsGenesSize differencesPathwayGlobal increaseRelevant mechanismsBiologyCentral challengeNeuroimmune dysfunctionRegionFunctionDiscoveryAutism spectrum disorderNasal 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
Long-read single molecule real-time (SMRT) sequencing of GBA1 locus in Gaucher disease national cohort from Argentina reveals high frequency of complex allele underlying severe skeletal phenotypes: Collaborative study from the Argentine Group for Diagnosis and Treatment of Gaucher Disease
Drelichman G, Escobar N, Soberon B, Basack N, Frabasil J, Schenone A, Aguilar G, Larroudé M, Knight J, Zhao D, Ruan J, Mistry PK, Disease A. Long-read single molecule real-time (SMRT) sequencing of GBA1 locus in Gaucher disease national cohort from Argentina reveals high frequency of complex allele underlying severe skeletal phenotypes: Collaborative study from the Argentine Group for Diagnosis and Treatment of Gaucher Disease. Molecular Genetics And Metabolism Reports 2021, 29: 100820. PMID: 34820281, PMCID: PMC8600149, DOI: 10.1016/j.ymgmr.2021.100820.Peer-Reviewed Original ResearchSevere skeletal manifestationsDiagnóstico y tratamientoSevere skeletal phenotypeGenotype/phenotype correlationGrupo ArgentinoNational cohortDisease manifestationsSkeletal manifestationsGaucher diseaseSkeletal diseaseLarge burdenDiseaseSkeletal phenotypePhenotype correlationComplex allelesArgentine groupCollaborative studyManifestationsChildhoodCollaborative groupsGroupHigh frequencyCohortCIDEA 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 correlationInduction of interferon signaling and allograft inflammatory factor 1 in macrophages in a mouse model of breast cancer metastases
Zheng W, Zhao D, Zhang H, Chinnasamy P, Sibinga N, Pollard JW. Induction of interferon signaling and allograft inflammatory factor 1 in macrophages in a mouse model of breast cancer metastases. Wellcome Open Research 2021, 6: 52. PMID: 33824914, PMCID: PMC8008350, DOI: 10.12688/wellcomeopenres.16569.2.Peer-Reviewed Original ResearchGene expression programsDifferent gene expression profilesGene-targeted mouse modelsGene expression profilesFactor 1Interferon-responsive genesAllograft inflammatory factor-1Metastatic breast cancer cellsExpression programsInflammatory factor-1Functional validationExpression profilesActivated pathwaysMetastatic growthC57BL6/J backgroundBreast cancer cellsSignificant enrichmentFunctional relevanceInterferon SignalingResident alveolar macrophagesBreast cancer metastasisQRT-PCRStrong upregulationCancer metastasisHuman macrophagesDynamic 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 replicationInduction of interferon signaling and allograft inflammatory factor 1 in macrophages in a mouse model of breast cancer metastases
Zheng W, Zhao D, Zhang H, Chinnasamy P, Sibinga N, Pollard J. Induction of interferon signaling and allograft inflammatory factor 1 in macrophages in a mouse model of breast cancer metastases. Wellcome Open Research 2021, 6: 52. DOI: 10.12688/wellcomeopenres.16569.1.Peer-Reviewed Original ResearchGene expression programsDifferent gene expression profilesGene-targeted mouse modelsGene expression profilesFactor 1Interferon-responsive genesAllograft inflammatory factor-1Metastatic breast cancer cellsExpression programsInflammatory factor-1Functional validationExpression profilesActivated pathwaysMetastatic growthC57BL6/J backgroundBreast cancer cellsSignificant enrichmentFunctional relevanceInterferon SignalingResident alveolar macrophagesBreast cancer metastasisQRT-PCRStrong upregulationCancer metastasisHuman macrophagesA 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
2020
Histone sumoylation promotes Set3 histone-deacetylase complex-mediated transcriptional regulation
Ryu HY, Zhao D, Li J, Su D, Hochstrasser M. Histone sumoylation promotes Set3 histone-deacetylase complex-mediated transcriptional regulation. Nucleic Acids Research 2020, 48: gkaa1093-. PMID: 33231641, PMCID: PMC7708062, DOI: 10.1093/nar/gkaa1093.Peer-Reviewed Original ResearchConceptsHistone deacetylase complexSet3 histone deacetylase complexHistone sumoylationTrans-tail regulationGenome-wide analysisSUMO-interacting motifSUMO conjugation pathwayAltered gene expression profilesDeacetylation of histonesGene expression profilesSet3 complexH2B ubiquitylationDeacetylase complexSpurious transcriptionRNA genesTranscriptional regulationActive genesTranscriptional fidelityTranscription initiationSUMOylationMRNA genesExpression profilesCrosstalk pathwaysHistone deacetylaseGenes
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 programsCD44The Ulp2 SUMO protease promotes transcription elongation through regulation of histone sumoylation
Ryu H, Su D, Wilson‐Eisele N, Zhao D, López‐Giráldez F, Hochstrasser M. The Ulp2 SUMO protease promotes transcription elongation through regulation of histone sumoylation. The EMBO Journal 2019, 38: e102003. PMID: 31313851, PMCID: PMC6694223, DOI: 10.15252/embj.2019102003.Peer-Reviewed Original ResearchConceptsSmall ubiquitin-like modifierRNA polymerase IIC-terminal domainHistone sumoylationTranscription elongationActive genesSUMO proteaseRNAPII C-terminal domainChromatin regulatory mechanismsTranscriptional elongation defectsUbiquitin-like modifierCtk1 kinaseH2B ubiquitylationEukaryotic proteinsNucleosome associationElongation defectsPolySUMO chainsPolymerase IITranscript elongationCUP1 geneUlp2Saccharomyces cerevisiaeRegulatory mechanismsImpaired associationSerine 2