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 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
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 formationReduced 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