2024
Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains
Zhu B, Park J, Coffey S, Russo A, Hsu I, Wang J, Su C, Chang R, Lam T, Gopal P, Ginsberg S, Zhao H, Hafler D, Chandra S, Zhang L. Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains. Science Translational Medicine 2024, 16: eabo1997. PMID: 39475571, DOI: 10.1126/scitranslmed.abo1997.Peer-Reviewed Original ResearchConceptsProteomic analysisAlzheimer's diseasePrefrontal cortexBrain cell typesGenetics of PDParkinson's diseaseCell-cell interactionsChaperone expressionSingle-nucleus transcriptomesExpressed genesTranscriptional changesPostmortem human brainPostmortem brain tissueDiseased brainSynaptic proteinsSingle-cellDown-regulationBrain cell populationsBrain regionsCell typesNeurodegenerative disordersLate-stage PDParkinson's disease brainsDisease etiologyNeuronal vulnerability
2023
scNAT: a deep learning method for integrating paired single-cell RNA and T cell receptor sequencing profiles
Zhu B, Wang Y, Ku L, van Dijk D, Zhang L, Hafler D, Zhao H. scNAT: a deep learning method for integrating paired single-cell RNA and T cell receptor sequencing profiles. Genome Biology 2023, 24: 292. PMID: 38111007, PMCID: PMC10726524, DOI: 10.1186/s13059-023-03129-y.Peer-Reviewed Original ResearchSingle-cell analysis reveals inflammatory interactions driving macular degeneration
Kuchroo M, DiStasio M, Song E, Calapkulu E, Zhang L, Ige M, Sheth A, Majdoubi A, Menon M, Tong A, Godavarthi A, Xing Y, Gigante S, Steach H, Huang J, Huguet G, Narain J, You K, Mourgkos G, Dhodapkar R, Hirn M, Rieck B, Wolf G, Krishnaswamy S, Hafler B. Single-cell analysis reveals inflammatory interactions driving macular degeneration. Nature Communications 2023, 14: 2589. PMID: 37147305, PMCID: PMC10162998, DOI: 10.1038/s41467-023-37025-7.Peer-Reviewed Original ResearchConceptsAge-related macular degenerationMacular degenerationNeurodegenerative diseasesNeurodegenerative conditionsLate-stage age-related macular degenerationPossible new therapeutic targetsPostmortem human retinaProgressive multiple sclerosisNew therapeutic targetsEarly phaseSingle-nucleus RNA sequencingInflammatory interactionsMultiple sclerosisInterleukin-1βDisease progressionControl retinasTherapeutic approachesGlial populationsGlial stateTherapeutic targetDisease pathogenesisRetinal diseasesAlzheimer's diseaseDiseaseHuman retina
2022
The immunology of Parkinson’s disease
Zhu B, Yin D, Zhao H, Zhang L. The immunology of Parkinson’s disease. Seminars In Immunopathology 2022, 44: 659-672. PMID: 35674826, PMCID: PMC9519672, DOI: 10.1007/s00281-022-00947-3.Peer-Reviewed Original ResearchConceptsAdaptive immune responsesImmune responseParkinson's diseaseT cellsGut-brain axis hypothesisOnset of PDΑ-synucleinGastro-intestinal symptomsCommon neurodegenerative disorderInnate immune responseΑ-synuclein aggregationPD patientsDopaminergic neuronsLewy bodiesSubstantia nigraNeuronal deathDisease progressionNeuropathological hallmarksProdromal phaseCurrent treatmentNeurodegenerative disordersDiseaseBrainMicrogliaPatientsReversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Pérez-Cañamás A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Science Translational Medicine 2022, 14: eabi8593. PMID: 35648810, PMCID: PMC9554345, DOI: 10.1126/scitranslmed.abi8593.Peer-Reviewed Original ResearchConceptsPositron emission tomographySilent allosteric modulatorsAlzheimer's diseaseMouse modelPhospho-tau accumulationAged mouse modelAlzheimer mouse modelImmune-mediated attackSAM treatmentMicroglial mediatorsSynaptic engulfmentSynaptic lossAD miceComplement component C1qSynapse lossGlutamate responseSynaptic densityDrug washoutSynaptic localizationTherapeutic benefitCognitive impairmentAllosteric modulatorsEmission tomographyNonhuman primatesComponent C1qA Markov random field model-based approach for differentially expressed gene detection from single-cell RNA-seq data
Zhu B, Li H, Zhang L, Chandra SS, Zhao H. A Markov random field model-based approach for differentially expressed gene detection from single-cell RNA-seq data. Briefings In Bioinformatics 2022, 23: bbac166. PMID: 35514182, PMCID: PMC9487630, DOI: 10.1093/bib/bbac166.Peer-Reviewed Original ResearchConceptsDE genesSeq dataSingle-cell RNA sequencing technologyDifferential expressionSingle-cell RNA-seq dataIdentification of genesRNA sequencing technologySpecific differential expressionSingle-cell resolutionRNA-seq dataMarkov random field modelMarkov random field model-based approachSimilar cell typesNovel statistical modelRandom field modelComplex biological systemsBiological pathwaysGene detectionGenesCell typesStatistical modelMouse datasetsField modelBiological systemsReal dataA multidimensional coding architecture of the vagal interoceptive system
Zhao Q, Yu CD, Wang R, Xu QJ, Dai Pra R, Zhang L, Chang RB. A multidimensional coding architecture of the vagal interoceptive system. Nature 2022, 603: 878-884. PMID: 35296859, PMCID: PMC8967724, DOI: 10.1038/s41586-022-04515-5.Peer-Reviewed Original ResearchPathological Role of Natural Killer Cells in Parkinson's Disease: A Systematic Review.
Zhang L, Zhang Y, Fan D. Pathological Role of Natural Killer Cells in Parkinson's Disease: A Systematic Review. Frontiers In Aging Neuroscience 2022, 14: 890816. PMID: 35663564, PMCID: PMC9157643, DOI: 10.3389/fnagi.2022.890816.Peer-Reviewed Original Research
2021
Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells
Franjic D, Skarica M, Ma S, Arellano JI, Tebbenkamp ATN, Choi J, Xu C, Li Q, Morozov YM, Andrijevic D, Vrselja Z, Spajic A, Santpere G, Li M, Zhang S, Liu Y, Spurrier J, Zhang L, Gudelj I, Rapan L, Takahashi H, Huttner A, Fan R, Strittmatter SM, Sousa AMM, Rakic P, Sestan N. Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells. Neuron 2021, 110: 452-469.e14. PMID: 34798047, PMCID: PMC8813897, DOI: 10.1016/j.neuron.2021.10.036.Peer-Reviewed Original ResearchConceptsDisease-related proteinsCellular diversityCross-species analysisSingle-nucleus transcriptomesLipid droplet proteinsSpecies-specific propertiesImmature neuron populationTranscriptomic taxonomyAlzheimer's disease-related proteinsEndoplasmic reticulumCell typesHuman neuronsSpecies differencesHistologic signatureNeurogenic capabilityProteinExcitatory neuronsDiversityAdult miceGranule cellsAlzheimer's diseaseNeuron populationsCognitive functionEntorhinal cellsAdult humansCirculating clonally expanded T cells reflect functions of tumor-infiltrating T cells
Lucca LE, Axisa PP, Lu B, Harnett B, Jessel S, Zhang L, Raddassi K, Zhang L, Olino K, Clune J, Singer M, Kluger HM, Hafler DA. Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells. Journal Of Experimental Medicine 2021, 218: e20200921. PMID: 33651881, PMCID: PMC7933991, DOI: 10.1084/jem.20200921.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsUnique transcriptional patternsFeatures of exhaustionLongitudinal immune monitoringPeripheral immune environmentsT cell responsesT cell functionSingle-cell levelTranscriptional patternsTCR sharingTerminal exhaustionImmune environmentImmune monitoringCancer immunotherapyMetastatic melanomaEffector functionsCell responsesTumor tissueGene signatureTumorsCell functionImmunotherapyTCRαβBlood
2020
Transcriptomic and clonal characterization of T cells in the human central nervous system
Pappalardo JL, Zhang L, Pecsok MK, Perlman K, Zografou C, Raddassi K, Abulaban A, Krishnaswamy S, Antel J, van Dijk D, Hafler DA. Transcriptomic and clonal characterization of T cells in the human central nervous system. Science Immunology 2020, 5 PMID: 32948672, PMCID: PMC8567322, DOI: 10.1126/sciimmunol.abb8786.Peer-Reviewed Original ResearchConceptsCentral nervous systemCSF of patientsT cellsCerebrospinal fluidMultiple sclerosisImmune surveillanceNervous systemCSF T cellsHuman central nervous systemHealthy human donorsT cell activationImmune dysfunctionNeuroinflammatory diseasesCytotoxic capacityHealthy donorsHealthy individualsCell activationHuman donorsTissue adaptationPatientsClonal characterizationExpression of genesCellsSurveillanceFurther characterization
2018
EED, a member of the polycomb group, is required for nephron differentiation and the maintenance of nephron progenitor cells
Zhang L, Ettou S, Khalid M, Taglienti M, Jain D, Jung YL, Seager C, Liu Y, Ng KH, Park PJ, Kreidberg JA. EED, a member of the polycomb group, is required for nephron differentiation and the maintenance of nephron progenitor cells. Development 2018, 145: dev157149. PMID: 29945864, PMCID: PMC6514390, DOI: 10.1242/dev.157149.Peer-Reviewed Original ResearchConceptsNephron progenitor cellsGene expressionProgenitor cellsNephron differentiationSelf-renewing stem cellsThousands of nephronsRole of PRC2Expression of genesDifferentiation of stemMutant micePolycomb groupH3K27me3 marksProgenitor stateEpigenetic regulationPRC2 complexHistone H3Progenitor populationsEnhancer sitesRenal vesiclesNonredundant componentMammalian kidneyCrucial rolePhysiological homeostasisGenesStem cellsProgressive cystic lesion in a middle-aged patient with tuberous sclerosis complex: A case report.
Zhang L, Jiang XY, Chen N, Hao NY, Zhou D, Li JM. Progressive cystic lesion in a middle-aged patient with tuberous sclerosis complex: A case report. Medicine 2018, 97: e0407. PMID: 29642206, PMCID: PMC5908606, DOI: 10.1097/MD.0000000000010407.Peer-Reviewed Original Research
2013
Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model
Liu B, Wang Z, Zhang L, Ghosh S, Zheng H, Zhou Z. Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. Nature Communications 2013, 4: 1868. PMID: 23695662, PMCID: PMC3674265, DOI: 10.1038/ncomms2885.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDisease Models, AnimalDNA DamageDNA RepairEnzyme StabilityFibroblastsHEK293 CellsHeterochromatinHistonesHumansLamin Type ALongevityLysineMethylationMethyltransferasesMiceNuclear ProteinsProgeriaProtein BindingProtein PrecursorsProtein Processing, Post-TranslationalRepressor ProteinsConceptsHutchinson-Gilford progeria syndromeBody weight lossBone mineral densityProgeria syndromeDNA repair capacityMineral densityMouse modelProgeria mouse modelG608G mutationSyndromeWeight lossProgeroid featuresRepair capacityH3K9me3 levelsPremature agingG mutationPotential strategyEpigenetic alterations
2011
Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses
Goffin D, Allen M, Zhang L, Amorim M, Wang IT, Reyes AR, Mercado-Berton A, Ong C, Cohen S, Hu L, Blendy JA, Carlson GC, Siegel SJ, Greenberg ME, Zhou Z. Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses. Nature Neuroscience 2011, 15: 274-283. PMID: 22119903, PMCID: PMC3267879, DOI: 10.1038/nn.2997.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAge FactorsAlanineAnimalsCells, CulturedCerebral CortexChromatin ImmunoprecipitationConditioning, PsychologicalDNA Mutational AnalysisDNA-Binding ProteinsElectroencephalographyEmbryo, MammalianEvoked Potentials, Auditory, Brain StemExploratory BehaviorFearGene Expression RegulationHumansMaze LearningMethyl-CpG-Binding Protein 2MiceMice, Inbred C57BLMice, TransgenicMotor ActivityMutationNeuronsSpectrum AnalysisThreonineHistone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice
Krishnan V, Chow MZ, Wang Z, Zhang L, Liu B, Liu X, Zhou Z. Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 12325-12330. PMID: 21746928, PMCID: PMC3145730, DOI: 10.1073/pnas.1102789108.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAgingAging, PrematureAnimalsCells, CulturedCellular SenescenceChromosomal Proteins, Non-HistoneDisease Models, AnimalDNA RepairDNA-Binding ProteinsHistone AcetyltransferasesHistone Deacetylase InhibitorsHistonesHumansLamin Type ALysineMembrane ProteinsMetalloendopeptidasesMiceMice, KnockoutNuclear MatrixNuclear ProteinsProtein PrecursorsRNA, Small InterferingTumor Suppressor p53-Binding Protein 1ConceptsDNA damage responseHutchinson-Gilford progeria syndromeDamage responseProgeria syndromeRepair protein recruitmentDNA damage sitesZmpste24-deficient miceAge-associated phenotypesDefective DNA repairChromatin modificationsProtein recruitmentEpigenetic marksHistone H4Histone acetyltransferaseNuclear matrixSpecific point mutationsDNA repairLamin AGenomic instabilityEpigenetic changesRepair proteinsHistone deacetylase inhibitorsCellular senescenceMOF overexpressionMolecular mechanisms