Yile Dai
Research
Publications
2026
Off-target reactivity in clinical monoclonal antibodies
Dai Y, Brouillard J, Jaycox J, Yeon S, Huck J, Yandamuri S, Zhong Z, O'Connor K, Burnina I, Henkel C, LeMay A, Lilov A, McGurk E, Morrill M, Parker L, Sackett T, Sandberg C, Sivasubramanian A, Geoghegan J, Ring A. Off-target reactivity in clinical monoclonal antibodies. Structure 2026 PMID: 41850278, DOI: 10.1016/j.str.2026.02.012.Peer-Reviewed Original ResearchMonoclonal antibodiesOff-target reactivityClinical monoclonal antibodiesHuman extracellular proteinsOff-target interactionsOff-target bindingOff-target hitsFDA approvalAntibody specificityProtein familyExtracellular proteinsAntibodiesTherapeutic antibodiesEpitope mimicryBiophysical analysisDrug developmentBiological drug developmentVariable domainsProteinClinical-stage antibodiesTarget affinityTanezumab
2025
CTLA-4 blockade shifts the B cell repertoire towards autoimmunity
Çakan E, Wang M, Dai Y, Mirouse A, Villanueva-Pachas C, Bouis D, Boeckers J, Gera R, Yraita S, Clapp L, Perdigoto A, Delmotte F, Massad C, Bacchiocchi A, Ring A, Kluger Y, Kluger H, Herold K, Meffre E. CTLA-4 blockade shifts the B cell repertoire towards autoimmunity. Journal Of Clinical Investigation 2025, 135: e189074. PMID: 41026527, PMCID: PMC12618075, DOI: 10.1172/jci189074.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsAnti-PD-1CTLA-4 blockadeMature naive B cellsCTLA-4Naive B cellsB cell repertoireB cellsCheckpoint inhibitorsPD-1Emergence of immune-related adverse eventsAnti-CTLA-4 combination therapyCancer patientsReactivity of recombinant antibodiesCentral B cell tolerancePeripheral B cell repertoireAnti-CTLA-4B cell frequenciesBlood of cancer patientsAutoreactive B cellsB cell toleranceTreatment of cancer patientsSingle B cellsAntitumor responseCombination therapyHumoral 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 factorTick feeding or vaccination with tick antigens elicits immunity to the Ixodes scapularis exoproteome in guinea pigs and humans
Hart T, Cui Y, Telford S, Marín-López A, Calloway K, Dai Y, Matias J, DePonte K, Jaycox J, DeBlasio M, Hoornstra D, Belperron A, Cibichakravarthy B, Johnson E, Alameh M, Dwivedi G, Hovius J, Bockenstedt L, Weissman D, Ring A, Fikrig E. Tick feeding or vaccination with tick antigens elicits immunity to the Ixodes scapularis exoproteome in guinea pigs and humans. Science Translational Medicine 2025, 17: eads9207. PMID: 40138454, PMCID: PMC12067475, DOI: 10.1126/scitranslmed.ads9207.Peer-Reviewed Original ResearchConceptsTick antigensTick resistanceVector of tick-borne pathogensAcquired tick resistanceTick-borne pathogensIxodes scapularisTick feedingAntitick vaccinesDetectable antibody responseGuinea pigsTicksTick bitesAntigen cocktailPigsPrimary vectorFeedingAntibody responseHumoral responseImmunogen candidateAntigenLyme diseaseImmunoglobulin GRepeated exposureIxodesNorth America
2024
A host–microbiota interactome reveals extensive transkingdom connectivity
Sonnert N, Rosen C, Ghazi A, Franzosa E, Duncan-Lowey B, González-Hernández J, Huck J, Yang Y, Dai Y, Rice T, Nguyen M, Song D, Cao Y, Martin A, Bielecka A, Fischer S, Guan C, Oh J, Huttenhower C, Ring A, Palm N. A host–microbiota interactome reveals extensive transkingdom connectivity. Nature 2024, 628: 171-179. PMID: 38509360, DOI: 10.1038/s41586-024-07162-0.Peer-Reviewed Original ResearchNiche colonizationHost–microorganism interactionsHost-microbiota interactionsInvade host tissuesStrain-specific interactionsHost cells in vitroConspecific strainsEffect of indigenous microorganismsHost biologyHost proteinsSecreted proteinsCommensal microorganismsExoproteinsBacterial strainsDiverse phylogenyMolecular basisMyriad microorganismsTissue of originTissue isolationCells in vitroInteractomeBinding patternsHost tissuesBiological logicHost immune system in vivo
2023
Distinguishing features of long COVID identified through immune profiling
Klein J, Wood J, Jaycox J, Dhodapkar R, Lu P, Gehlhausen J, Tabachnikova A, Greene K, Tabacof L, Malik A, Silva Monteiro V, Silva J, Kamath K, Zhang M, Dhal A, Ott I, Valle G, Peña-Hernández M, Mao T, Bhattacharjee B, Takahashi T, Lucas C, Song E, McCarthy D, Breyman E, Tosto-Mancuso J, Dai Y, Perotti E, Akduman K, Tzeng T, Xu L, Geraghty A, Monje M, Yildirim I, Shon J, Medzhitov R, Lutchmansingh D, Possick J, Kaminski N, Omer S, Krumholz H, Guan L, Dela Cruz C, van Dijk D, Ring A, Putrino D, Iwasaki A. Distinguishing features of long COVID identified through immune profiling. Nature 2023, 623: 139-148. PMID: 37748514, PMCID: PMC10620090, DOI: 10.1038/s41586-023-06651-y.Peer-Reviewed Original ResearchConceptsLong COVIDSARS-CoV-2Infection syndromeExaggerated humoral responseSoluble immune mediatorsEpstein-Barr virusPost-exertional malaiseCross-sectional studyHigher antibody responseImmune mediatorsImmune phenotypingImmune profilingHumoral responseAntibody responseLymphocyte populationsCOVID statusUnbiased machineCortisol levelsLC statusRelevant biomarkersViral pathogensSyndromeCOVIDFuture studiesBiological featuresInvestigating Autoantibody Profiles in Seronegative Myasthenia Gravis (P1-5.005)
Masi G, Pham M, Dai Y, Li Y, Karatz T, Oxendine S, Juel V, Ring A, Nowak R, Guptill J, O’Connor K. Investigating Autoantibody Profiles in Seronegative Myasthenia Gravis (P1-5.005). Neurology 2023, 100 DOI: 10.1212/wnl.0000000000202639.Peer-Reviewed Original Research
2021
Diverse functional autoantibodies in patients with COVID-19
Wang EY, Mao T, Klein J, Dai Y, Huck JD, Jaycox JR, Liu F, Zhou T, Israelow B, Wong P, Coppi A, Lucas C, Silva J, Oh JE, Song E, Perotti ES, Zheng NS, Fischer S, Campbell M, Fournier JB, Wyllie AL, Vogels CBF, Ott IM, Kalinich CC, Petrone ME, Watkins AE, Dela Cruz C, Farhadian S, Schulz W, Ma S, Grubaugh N, Ko A, Iwasaki A, Ring A. Diverse functional autoantibodies in patients with COVID-19. Nature 2021, 595: 283-288. PMID: 34010947, DOI: 10.1038/s41586-021-03631-y.Peer-Reviewed Original ResearchConceptsPeripheral immune cell compositionSARS-CoV-2 infectionCOVID-19Effects of autoantibodiesTissue-associated antigensSpecific clinical characteristicsInnate immune activationImmune cell compositionCOVID-19 exhibitCOVID-19 manifestsAnalysis of autoantibodiesSARS-CoV-2Functional autoantibodiesMouse surrogateClinical characteristicsVirological controlClinical outcomesImmune activationMild diseaseAsymptomatic infectionAutoantibody reactivityDisease progressionHealthcare workersHigh prevalenceAutoantibodiesNeuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection