Le Zhang, PhD
Assistant Professor of Neurology and of NeuroscienceCards
About
Research
Publications
2026
Shared 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 PMID: 41826324, 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 burdenThe 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
Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma
Schoenfeld D, Djureinovic D, Su D, Zhang L, Lu B, Kamga L, Mann J, Huck J, Hurwitz M, Braun D, Jilaveanu L, Ring A, Kluger H. Decoy-resistant IL-18 reshapes the tumor microenvironment and enhances rejection by anti-CTLA-4 in renal cell carcinoma. JCI Insight 2024, 10: e184545. PMID: 39561007, PMCID: PMC11721305, DOI: 10.1172/jci.insight.184545.Peer-Reviewed Original ResearchAnti-CTLA-4Renal cell carcinomaIL-18IL-18BPCell carcinomaTumor microenvironmentTumor typesPatients treated with immune checkpoint inhibitorsRegulatory T cell levelsAnti-PD-1 treatmentCD8+ T cellsAnti-PD-1Immune checkpoint inhibitorsCell renal cell carcinomaNon-responder patientsMyeloid cell populationsT cell levelsCytokine interleukin-18Anti-cancer efficacySecreted binding proteinCheckpoint inhibitorsResponding patientsPreclinical modelsT cellsMurine modelSingle-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 Research
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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Events
Apr 202623Thursday
Yale Only Akiko Iwasaki, PhD - Noah Wolcott Palm, PhD - Emilia Favuzzi, PhD - Shawn Ferguson, PhD - Le Zhang, PhD - David R. Martinez, PhD - Yifei Cai