Le Zhang, PhD
Assistant Professor of Neurology and of NeuroscienceCards
About
Research
Publications
2026
Lineage and organ signals sequentially build organ intrinsic nervous systems.
Hsu IY, Zhao J, Lin Y, Guo Y, Xu QJ, Shao Y, Wang RL, Yin D, Ghoshal K, Mourad R, Pozzi A, Halabi CM, Young LH, Zhao H, Zhang L, Chang RB. Lineage and organ signals sequentially build organ intrinsic nervous systems. Nature 2026 PMID: 42129551, DOI: 10.1038/s41586-026-10490-y.Peer-Reviewed Original ResearchShared genetic and neuroimmune architecture links type 1 diabetes with neurocognitive traits
Saarah P, Syeda Z, Xu Z, Dong Y, Jiang H, Shanguyhia M, Roy S, Zhu B, Zhang L, Dewan A, Asgari S, Alagpulinsa D. Shared genetic and neuroimmune architecture links type 1 diabetes with neurocognitive traits. Nature Communications 2026, 17: 4057. PMID: 41826324, PMCID: PMC13139607, DOI: 10.1038/s41467-026-70694-8.Peer-Reviewed Original ResearchNeurocognitive traitsGenome-wide associationType 1 diabetes riskGenetic correlation analysisConcordant differential expressionNeuropsychiatric disease riskFalse discovery rate analysisBipolar disorderPleiotropic lociRegulatory variantsType 1 diabetesProtective effects of educational attainmentDifferential expressionAlzheimer's diseaseEffects of educational attainmentExecutive functionTraitsMendelian randomizationBiological mechanismsDisease-affectedNeuroimmune mechanismsChildhood onsetDisease riskRisk of myasthenia gravisEducational attainment
2025
Inferring spatial single-cell-level interactions through interpreting cell state and niche correlations learned by self-supervised graph transformer
Xiao X, Zhang L, Zhao H, Wang Z. Inferring spatial single-cell-level interactions through interpreting cell state and niche correlations learned by self-supervised graph transformer. Nature Machine Intelligence 2025, 8: 42-58. DOI: 10.1038/s42256-025-01161-0.Peer-Reviewed Original ResearchCell-cell interactionsGene expressionCell statesCell-cell interaction networkSpatial transcriptomics datasetsSingle-cell resolutionSender cellsLigand-receptor pairsTranscriptomic datasetsMultiple speciesReceiver cellsTissue developmentCentral cellCell-cell interaction patternsSpatial transcriptomicsCell clustersCellular neighborhoodsNicheCellsImproving immunotherapy responses by dual inhibition of macrophage migration inhibitory factor and PD-1
Tran T, Sánchez-Zuno G, Osmani L, Caulfield J, Valdez C, Piecychna M, Leng L, Armstrong M, Donnelly S, Bifulco C, Clister T, Kulkarni R, Zhang L, Sznol M, Jilaveanu L, Kluger H, Kang I, Bucala R. Improving immunotherapy responses by dual inhibition of macrophage migration inhibitory factor and PD-1. JCI Insight 2025, 10: e191539. PMID: 41122966, PMCID: PMC12581657, DOI: 10.1172/jci.insight.191539.Peer-Reviewed Original ResearchConceptsAnti-PD-1Macrophage migration inhibitory factorAnti-MIFMigration inhibitory factorTumor growthTherapeutic efficacyAnti-programmed cell death 1Intratumoral immune cell populationsAssociated with advanced diseaseHigh-expression MIF allelesCell death 1Inhibitory factorTh1 cytokine levelsInhibition of macrophage migration inhibitory factorDual inhibitionMurine tumor modelsColorectal cancer modelImmune cell populationsTumor-bearing animalsClinical trial developmentMultiple cancer typesAntitumor responseDeath-1PD-1Tumor burdenToward Imaging of the GABA Transporter Type 1 In Vivo: Quantitative Evaluation of 4 Novel PET Radiotracers in Nonhuman Primates
Gravel P, Gu J, Wang C, Volpi T, Gallezot J, Holden D, Fowles K, Zheng M, Zhang L, Borroni E, Honer M, Gobbi L, Tamagnan G, Huang Y, Carson R. Toward Imaging of the GABA Transporter Type 1 In Vivo: Quantitative Evaluation of 4 Novel PET Radiotracers in Nonhuman Primates. Journal Of Nuclear Medicine 2025, 66: 1652-1658. PMID: 40908122, PMCID: PMC12487869, DOI: 10.2967/jnumed.125.270332.Peer-Reviewed Original ResearchGABA transporter type 1Nonhuman primatesGAT-1Brain uptakeNondisplaceable binding potentialSubcortical gray matter regionsHuman studiesG-aminobutyric acidLow brain uptakeGray matter structuresLow specific bindingConclusion:Methods:Gray matter regionsType 1Results:Neuropsychiatric disordersPET radiotracersBinding potentialGABA signalingVolume of distributionMatter structuresRhesus monkeysBlock scanningGABA receptorsHumoral determinants of checkpoint immunotherapy
Dai Y, Aizenbud L, Qin K, Austin M, Jaycox J, Cunningham J, Wang E, Zhang L, Fischer S, Carroll S, van Aggelen H, Kluger Y, Herold K, Furchtgott L, Kluger H, Ring A. Humoral determinants of checkpoint immunotherapy. Nature 2025, 644: 527-536. PMID: 40702172, DOI: 10.1038/s41586-025-09188-4.Peer-Reviewed Original ResearchConceptsCheckpoint immunotherapyPreclinical mouse tumor modelsImmune-related adverse eventsIFN-IAntibody-mediated humoral immunityResponse to therapyTumor surface proteinMouse tumor modelsType I interferonIndividual autoantibodiesAutoantibody signaturesAdverse eventsAutoantibody responseCellular immunityTumor modelHumoral immunityAutoantibodiesOdds ratioIL-6Healthy control participantsHealthy individualsControl individualsI interferonPatientsGrowth factorThe 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, PMCID: PMC12768464, 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
CosGeneGate selects multi-functional and credible biomarkers for single-cell analysis
Liu T, Long W, Cao Z, Wang Y, He C, Zhang L, Strittmatter S, Zhao H. CosGeneGate selects multi-functional and credible biomarkers for single-cell analysis. Briefings In Bioinformatics 2024, 26: bbae626. PMID: 39592241, PMCID: PMC11596696, DOI: 10.1093/bib/bbae626.Peer-Reviewed Original ResearchSingle-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-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 vulnerability
Academic Achievements & Community Involvement
News
News
- June 03, 2026Source: Yale News
Beyond the Brain: Organs Help Shape the Nervous Systems that Control Them
- 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
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