Le Zhang, PhD
Assistant Professor of Neurology and of NeuroscienceCards
About
Research
Publications
2025
The subfornical organ is a nucleus for gut-derived T cells that regulate behaviour
Yoshida T, Nguyen M, Zhang L, Lu B, Zhu B, Murray K, Mineur Y, Zhang C, Xu D, Lin E, Luchsinger J, Bhatta S, Waizman D, Coden M, Ma Y, Israni-Winger K, Russo A, Wang H, Song W, Al Souz J, Zhao H, Craft J, Picciotto M, Grutzendler J, Distasio M, Palm N, Hafler D, Wang A. The subfornical organ is a nucleus for gut-derived T cells that regulate behaviour. Nature 2025, 643: 499-508. PMID: 40437096, DOI: 10.1038/s41586-025-09050-7.Peer-Reviewed Original ResearchMeningeal T cellsCentral nervous systemT cellsSubfornical organCD4 T cellsInnate immune compartmentGut-brain axisSteady-state brainGut microbiotaSpecialized immune cellsCentral nervous system homeostasisAdaptive immune systemBiological functionsImmune compartmentGut-derived T cellsImmune cellsWhite adiposeImmune systemNervous systemAdipose tissueComposition of adipose tissueGastrointestinal tissuesWell-characterizedHomeostasisBrainTranscriptomic profiling after B-cell depletion reveals central and peripheral immune cell changes in multiple sclerosis
Wei J, Moon J, Yasumizu Y, Zhang L, Raddassi K, Buitrago-Pocasangre N, Deerhake M, Strauli N, Chen C, Herman A, Pedotti R, Raposo C, Yim I, Pappalardo J, Longbrake E, Sumida T, Axisa P, Hafler D. Transcriptomic profiling after B-cell depletion reveals central and peripheral immune cell changes in multiple sclerosis. Journal Of Clinical Investigation 2025, 135: e182790. PMID: 40067358, PMCID: PMC12126227, DOI: 10.1172/jci182790.Peer-Reviewed Original ResearchConceptsB-cell depletionImmune landscapeMultiple sclerosisAnti-CD20-mediated B-cell depletionPeripheral CD4+ T cell populationsEffect of B cell depletionB cell depletion treatmentCD4+ T cell populationB cell depletion therapyCerebrospinal fluidCD4+ T cellsTreatment of early diseaseCD16+ monocytesImmune cell changesImmune cell subsetsT cell populationsPeripheral blood monocytesFlow cytometry-based methodTNF-a mRNACell type-specific changesCell subsetsT cellsImmunological changesAutoimmune activityB cells
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, PMCID: PMC12372474, 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 vulnerabilityThe single-cell opioid responses in the context of HIV (SCORCH) consortium
Ament S, Campbell R, Lobo M, Receveur J, Agrawal K, Borjabad A, Byrareddy S, Chang L, Clarke D, Emani P, Gabuzda D, Gaulton K, Giglio M, Giorgi F, Gok B, Guda C, Hadas E, Herb B, Hu W, Huttner A, Ishmam M, Jacobs M, Kelschenbach J, Kim D, Lee C, Liu S, Liu X, Madras B, Mahurkar A, Mash D, Mukamel E, Niu M, O’Connor R, Pagan C, Pang A, Pillai P, Repunte-Canonigo V, Ruzicka W, Stanley J, Tickle T, Tsai S, Wang A, Wills L, Wilson A, Wright S, Xu S, Yang J, Zand M, Zhang L, Zhang J, Akbarian S, Buch S, Cheng C, Corley M, Fox H, Gerstein M, Gummuluru S, Heiman M, Ho Y, Kellis M, Kenny P, Kluger Y, Milner T, Moore D, Morgello S, Ndhlovu L, Rana T, Sanna P, Satterlee J, Sestan N, Spector S, Spudich S, Tilgner H, Volsky D, White O, Williams D, Zeng H. The single-cell opioid responses in the context of HIV (SCORCH) consortium. Molecular Psychiatry 2024, 29: 3950-3961. PMID: 38879719, PMCID: PMC11609103, DOI: 10.1038/s41380-024-02620-7.Peer-Reviewed Original ResearchContext of human immunodeficiency virusHuman immunodeficiency virusSubstance use disordersOpioid responseAnimal modelsEffects of substance use disordersOpioid pain medicationsPrevalence of co-morbid conditionsChronic pain syndromesStage of diseaseCell typesAffected cell typesCo-morbid conditionsPain syndromeImmunodeficiency virusPain medicationOpioid addictionIncreased riskRisk factorsHuman cohortsDrug addictionBrain tissue collectionBrain cell typesTissue collectionSingle-cell levelSingle-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE)
Hanin A, Zhang L, Huttner A, Plu I, Mathon B, Bielle F, Navarro V, Hirsch L, Hafler D. Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE). Neurology Neuroimmunology & Neuroinflammation 2024, 11: e200259. PMID: 38810181, PMCID: PMC11139018, DOI: 10.1212/nxi.0000000000200259.Peer-Reviewed Original ResearchConceptsNew-onset refractory status epilepticusTemporal lobe epilepsyGABAergic neuronsExcitatory neuronsInfiltrating MacrophagesProportion of GABAergic neuronsChronic temporal lobe epilepsyRefractory status epilepticusInhibitory GABAergic neuronsSingle-cell transcriptome analysisDecreased expression of genesDegree of demyelinationImmune disturbancesNeuronal excitabilityImmune dysregulationNew-onsetStatus epilepticusPoor outcomeRefractory epilepsyHealthy childrenMicroglial reactivitySingle-nucleus RNA sequencingNLRP3 inflammasome activationInflammatory responseLobe epilepsy
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 data
Academic Achievements & Community Involvement
News
News
- June 30, 2025
Biomedical Research Saves Human Lives
- November 07, 2024
Parkinson’s Disease Associated With Neuroinflammation in the Brain, New Analyses Reveal
- July 23, 2024
Advancements in Women’s Health Research
- March 16, 2022
Revealing Communications Between Brain and Body
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Apr 202623Thursday
Yale Only Emilia Favuzzi, PhD - Shawn Ferguson, PhD - Yifei Cai - David R. Martinez, PhD - Le Zhang, PhD - Noah Wolcott Palm, PhD - Akiko Iwasaki, PhD