2025
Investigation of tumor-associated macrophages (TAMs) and therapeutic resistance to immune checkpoint inhibitors (ICI) through single-cell analysis of renal cell carcinoma (RCC).
Kashima S, Rout R, Hugaboom M, Ye Z, Schindler N, Malik R, Dighe A, Sun M, Lee G, Xu W, Signoretti S, Schoenfeld D, Hurwitz M, Adeniran A, Humphrey P, Kenney P, McGregor B, McKay R, Choueiri T, Braun D. Investigation of tumor-associated macrophages (TAMs) and therapeutic resistance to immune checkpoint inhibitors (ICI) through single-cell analysis of renal cell carcinoma (RCC). Journal Of Clinical Oncology 2025, 43: 4527-4527. DOI: 10.1200/jco.2025.43.16_suppl.4527.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsTumor-associated macrophagesRenal cell carcinomaICI-based therapyRCC tumor microenvironmentTumor microenvironmentNon-respondersGene programResistance to immune checkpoint inhibitorsImmune checkpoint inhibitor resistanceTumor-associated macrophage populationSuppress antitumor immunityWilcoxon Signed Rank TestInterferon-stimulated genesMechanisms of resistanceCheckpoint inhibitorsAntitumor immunityStable diseaseSystemic therapyCombination therapyCell carcinomaPotential therapeutic targetTreatment resistanceAntigen presentationTumor samplesCutaneous lupus features specialized stromal niches and altered retroelement expression
Gehlhausen J, Kong Y, Baker E, Ramachandran S, Koumpouras F, Ko C, Vesely M, Little A, Damsky W, King B, Iwasaki A. Cutaneous lupus features specialized stromal niches and altered retroelement expression. Journal Of Investigative Dermatology 2025 PMID: 40409678, DOI: 10.1016/j.jid.2025.04.033.Peer-Reviewed Original ResearchRetroelement expressionCGAS-STING pathwayRIG-IType I interferonCutaneous lupusCGAS-STINGElevated expression of genesPathway enrichment analysisI interferonExpression of genesResponse to type I interferonsLupus skinRetroelement familiesInterferon-stimulated genesNucleic acid signalsApoptotic signalingSingle-cell RNAMultiple cell typesAcid signalingEnrichment analysisInflammatory cell recruitmentType II interferonInflammatory skin diseaseTumor necrosis factorCell typesSARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults’ responses
Nehar-Belaid D, Mejías A, Xu Z, Marches R, Yerrabelli R, Chen G, Mertz S, Ye F, Sánchez P, Tsang J, Aydillo T, Miorin L, Cupic A, García-Sastre A, Ucar D, Banchereau J, Pascual V, Ramilo O. SARS-CoV-2 induced immune perturbations in infants vary with disease severity and differ from adults’ responses. Nature Communications 2025, 16: 4562. PMID: 40379618, PMCID: PMC12084365, DOI: 10.1038/s41467-025-59411-z.Peer-Reviewed Original ResearchConceptsResponse to SARS-CoV-2Infected infantsT cellsSARS-CoV-2B cellsCytotoxic CD8+ T cellsImmune profile of childrenISG signatureNaive CD4+ T cellsCD8+ T cellsCD4+ T cellsImmune response to SARS-CoV-2Anti-IFN autoantibodiesAntibody response to SARS-CoV-2Transitional B cellsEarly life immunityCD14+ monocytesIncreased serum concentrationsInflammasome-related moleculesInterferon-stimulated genesImmune profileImmune perturbationsSerum concentrationsInflammatory cytokinesImmune responseHSPA2 influences the differentiation and production of immunomodulatory mediators in human immortalized epidermal keratinocyte lines
Gogler A, Wilk A, Sojka D, Adamiec-Organiściok M, Matysiak N, Kania D, Wiecha K, Małusecka E, Cortez A, Zamojski D, Marczyk M, Mazurek A, Oziębło S, Scieglinska D. HSPA2 influences the differentiation and production of immunomodulatory mediators in human immortalized epidermal keratinocyte lines. Cell Death & Disease 2025, 16: 344. PMID: 40287440, PMCID: PMC12033329, DOI: 10.1038/s41419-025-07565-5.Peer-Reviewed Original ResearchConceptsChaperone proteinsKeratinocyte differentiationCell type-specific expression patternsHomologous chaperone proteinsEpidermal keratinocyte differentiationInterferon-mediated signalingInterferon-stimulated genesControl proteostasisExtracellular secretionTranscriptome analysisMolecular machineryKeratinocyte differentiation markersHSPA2Upper epidermal layersDifferentiation defectsExpression patternsSomatic cellsMolecular networksPro-inflammatory IL-6 cytokinePotential therapeutic targetFunctional analysisSecretion of IL-6Keratinocyte linePathogenic factorsReduced levelsPhospholipid scramblase 1: a frontline defense against viral infections
Yang A, Norbrun C, Sorkhdini P, Zhou Y. Phospholipid scramblase 1: a frontline defense against viral infections. Frontiers In Cellular And Infection Microbiology 2025, 15: 1573373. PMID: 40248364, PMCID: PMC12003403, DOI: 10.3389/fcimb.2025.1573373.Peer-Reviewed Original ResearchConceptsPhospholipid scramblase 1Human immunodeficiency virusInfluenza A virusToll-like receptor 9Human T-cell leukemia virus type 1Epstein-Barr virusHepatitis B virusInterferon-stimulated genesViral infectionHuman cytomegalovirusVirus type 1Antiviral activityTranslocation of phospholipidsFrontline defenseTransactivation of human immunodeficiency virusImmunodeficiency virusActivation of JAK/STAT pathwayImmune cellsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virusB virusReceptor 9Respiratory syndrome coronavirus 2Entry of severe acute respiratory syndrome coronavirus 2Therapeutic JAK inhibition does not impact lung injury during viral or bacterial pneumonia in male mice
Sharma L, Singh R, Ngeow C, van der Geest R, Duray A, Tolman N, McVerry B, Dela Cruz C, Alcorn J, Bain W, Robinson K. Therapeutic JAK inhibition does not impact lung injury during viral or bacterial pneumonia in male mice. Physiological Reports 2025, 13: e70232. PMID: 39921246, PMCID: PMC11805821, DOI: 10.14814/phy2.70232.Peer-Reviewed Original ResearchConceptsMurine model of influenzaIL-6 deletionMRSA pneumoniaModel of influenzaInflammatory cell recruitmentIL-6Interferon-stimulated genesMurine modelCell recruitmentJAK inhibitionElevated levels of IL-6Tissue injuryLevels of IL-6IL-6 deficiencyJAK inhibitor baricitinibSuppression of cytokinesLimit tissue injuryLung tissue injurySecondary bacterial infectionInfluenza infectionJAK/STAT signaling pathwayBaricitinib treatmentInhibitory therapyClinical efficacyBacterial burdenAcute inflammation induces acute megakaryopoiesis with impaired platelet production during fetal hematopoiesis.
Hu X, He Y, Li S, Jiang Y, Yu R, Wu Y, Fu X, Song Y, Lin C, Shi J, Li H, Gao Y. Acute inflammation induces acute megakaryopoiesis with impaired platelet production during fetal hematopoiesis. Development 2025, 152 PMID: 39817838, DOI: 10.1242/dev.204226.Peer-Reviewed Original ResearchFetal hematopoiesisMegakaryocyte-erythroid progenitorsAcute inflammationInterferon-stimulated genesDouble-stranded RNAMegakaryocyte maturationPlatelet productionImpaired platelet productionFormation of double-stranded RNADownstream interferon-stimulated genesCell fate determinationRNA m6A modificationPhosphorylation of STAT1Hematopoietic progenitorsMegakaryocyte progenitorsHematopoietic cellsM6A methyltransferase METTL3Hematopoietic developmentGene expression analysisImmune responseMegakaryopoiesisHematopoiesisInflammationFate determinationIGF1 expressionInterferon-Stimulated Genes and Immune Metabolites as Broad-Spectrum Biomarkers for Viral Infections
Huang C, Laurent-Rolle M, Grove T, Hsu J. Interferon-Stimulated Genes and Immune Metabolites as Broad-Spectrum Biomarkers for Viral Infections. Viruses 2025, 17: 132. PMID: 39861921, PMCID: PMC11768885, DOI: 10.3390/v17010132.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsInterferon-stimulated genesReceiver Operating CharacteristicViral infectionAntiviral functionType I interferonTarget various stagesIFN-II interferonViral replicationClinical practiceDiagnostic potentialClinical applicationProtein levelsBiomarkersImmune defenseInfectionViral pathogensMetabolitesBroad spectrumGenesEffective translation
2024
Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract
Mao T, Kim J, Peña-Hernández M, Valle G, Moriyama M, Luyten S, Ott I, Gomez-Calvo M, Gehlhausen J, Baker E, Israelow B, Slade M, Sharma L, Liu W, Ryu C, Korde A, Lee C, Monteiro V, Lucas C, Dong H, Yang Y, Initiative Y, Gopinath S, Wilen C, Palm N, Dela Cruz C, Iwasaki A, Vogels C, Hahn A, Chen N, Breban M, Koch T, Chaguza C, Tikhonova I, Castaldi C, Mane S, De Kumar B, Ferguson D, Kerantzas N, Peaper D, Landry M, Schulz W, Grubaugh N. Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2319566121. PMID: 38648490, PMCID: PMC11067057, DOI: 10.1073/pnas.2319566121.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesRespiratory infectionsStrains of influenza A virusTreatment of respiratory viral infectionsRespiratory virus infectionsInfluenza A virusMouse model of COVID-19Respiratory viral infectionsNeomycin treatmentExpression of interferon-stimulated genesUpper respiratory infectionInterferon-stimulated gene expressionLower respiratory infectionsBroad spectrum of diseasesAdministration of neomycinRespiratory viral diseasesDisease to patientsUpper respiratory tractIntranasal deliveryCongenic miceIntranasal applicationNasal mucosaSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2A virus154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery
Robert S, Kiziltug E, Lu B, Arnal-Estape A, Nguyen D, Chiang V. 154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery. Neurosurgery 2024, 70: 35-36. DOI: 10.1227/neu.0000000000002809_154.Peer-Reviewed Original ResearchRadiation necrosisFluorescence-activated cell sortingInterferon-stimulated genesStereotactic radiosurgeryNatural killerMyeloid cellsImmune cellsRadiosurgical treatment of brain metastasesTreatment of brain metastasesCD4+ T cellsExpression of immune cellsMorbid side effectsTreatment of RNSubpopulations of myeloid cellsStereotactic radio surgeryMetastatic brain tumorsInvasive brain biopsyCellular immune profilesInflammatory immune responseCSF of patientsRN patientsBrain metastasesCD8+Immunotherapy optionsMetastatic tumorsLung Gene Expression Suggests Roles for Interferon-Stimulated Genes and Adenosine Deaminase Acting against RNA‑1 in Pathologic Responses to Diisocyanate
Wisnewski A, Liu J. Lung Gene Expression Suggests Roles for Interferon-Stimulated Genes and Adenosine Deaminase Acting against RNA‑1 in Pathologic Responses to Diisocyanate. Chemical Research In Toxicology 2024, 37: 476-485. PMID: 38494904, PMCID: PMC11748834, DOI: 10.1021/acs.chemrestox.3c00325.Peer-Reviewed Original ResearchLung gene expressionNonsensitized miceImmune-sensitizationType I interferon-stimulated genesI interferon-stimulated genesAllergen-induced asthmaChemical-induced asthmaMolecular pathwaysADAR-1Ovalbumin-induced asthmaRegulation of innateInterferon-stimulated genesGene transcriptionGene expressionPathological responseAdenosine Deaminase ActingMurine modelAsthma-likeNonsensitized hostsLevels up to 10-foldLung tissueInnate responseLungTissue damageMice
2023
CMPK2 restricts Zika virus replication by inhibiting viral translation
Pawlak J, Hsu J, Xia H, Han P, Suh H, Grove T, Morrison J, Shi P, Cresswell P, Laurent-Rolle M. CMPK2 restricts Zika virus replication by inhibiting viral translation. PLOS Pathogens 2023, 19: e1011286. PMID: 37075076, PMCID: PMC10150978, DOI: 10.1371/journal.ppat.1011286.Peer-Reviewed Original ResearchConceptsCytidine/uridine monophosphate kinase 2I interferon-stimulated genesZika virus replicationYellow fever virusAntiviral activityAntiviral effectVirus replicationKunjin virusType I interferon-stimulated genesFirst lineOverall antiviral responseHost's first lineEffective therapeutic interventionsViral translationBroad antiviral activityInterferon-stimulated genesGlobal health threatAntiviral treatmentFlaviviral infectionsPathogenic flavivirusesAntiviral functionDrug AdministrationTherapeutic interventionsAntiviral responseDengue virus
2022
Viperin triggers ribosome collision-dependent translation inhibition to restrict viral replication
Hsu JC, Laurent-Rolle M, Pawlak JB, Xia H, Kunte A, Hee JS, Lim J, Harris LD, Wood JM, Evans GB, Shi PY, Grove TL, Almo SC, Cresswell P. Viperin triggers ribosome collision-dependent translation inhibition to restrict viral replication. Molecular Cell 2022, 82: 1631-1642.e6. PMID: 35316659, PMCID: PMC9081181, DOI: 10.1016/j.molcel.2022.02.031.Peer-Reviewed Original ResearchConceptsInterferon-stimulated genesS-adenosyl methionineTranslation inhibitionRadical S-adenosyl methionineInnate immune responseIntegrated stress response pathwayStress response pathwaysViral RNA translationImmune responseAntiviral responseInnate immunityAntiviral mechanismTranslation regulatorsTranslational repressionViral replicationEnzymatic productDidehydro-CTPResponse pathwaysRNA translationViperinSAM activityPathwayInhibitionBroad spectrumReplication
2021
Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics
Cheemarla NR, Watkins TA, Mihaylova VT, Wang B, Zhao D, Wang G, Landry ML, Foxman EF. Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics. Journal Of Experimental Medicine 2021, 218: e20210583. PMID: 34128960, PMCID: PMC8210587, DOI: 10.1084/jem.20210583.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAngiotensin-Converting Enzyme 2Case-Control StudiesChemokine CXCL10COVID-19Disease SusceptibilityFemaleGene Expression ProfilingHost-Pathogen InteractionsHumansImmunity, InnateInterferonsMaleMiddle AgedNasopharynxPicornaviridae InfectionsSARS-CoV-2Viral LoadVirus ReplicationConceptsSARS-CoV-2 infectionSARS-CoV-2 exposureSARS-CoV-2Interferon-stimulated genesUpper respiratory tractRespiratory tractEarly SARS-CoV-2 infectionDynamic innate immune responseViral replicationSARS-CoV-2 replicationPatient nasopharyngeal samplesInnate immune responseLow infectious doseViral loadNasopharyngeal samplesImmune responseInfectious doseISG responseAntiviral responseInfection progressionViral transmissionLevel correlatesInfectionISG inductionInitial replicationDiversity in responses to oncolytic Lassa-vesicular stomatitis virus in patient-derived glioblastoma cells
Kim T, Puckett S, Zhang K, Herpai D, Ornelles D, Davis J, van den Pol A, Debinski W, Lyles D. Diversity in responses to oncolytic Lassa-vesicular stomatitis virus in patient-derived glioblastoma cells. Molecular Therapy Oncology 2021, 22: 232-244. PMID: 34514102, PMCID: PMC8424128, DOI: 10.1016/j.omto.2021.06.003.Peer-Reviewed Original ResearchGreen fluorescent proteinGlioblastoma cell linesCell deathCell linesLevels of viral gene expressionViral gene expressionExpression of interferon-stimulated genesLassa virus glycoproteinInterferon-stimulated genesRNA-seqIndividual cell linesLow passagePatient-derived cellsPatient-derived glioblastoma cellsExpressing green fluorescent proteinRNA sequencingInterferon pathway activationFluorescent proteinGene expressionGlioma stem-like cellsStem-like cellsStomatitis virusCell viability assayBrain Tumor CenterSusceptible cellsTranslational shutdown and evasion of the innate immune response by SARS-CoV-2 NSP14 protein
Hsu JC, Laurent-Rolle M, Pawlak JB, Wilen CB, Cresswell P. Translational shutdown and evasion of the innate immune response by SARS-CoV-2 NSP14 protein. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2101161118. PMID: 34045361, PMCID: PMC8214666, DOI: 10.1073/pnas.2101161118.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Interferon-stimulated genesImmune responseSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Host protein synthesisRespiratory syndrome coronavirus 2Syndrome coronavirus 2Innate immune responseUnprecedented global health crisisCoronavirus 2N7-methyltransferase activityOngoing COVID-19 pandemicHuman coronavirusesTranslational shutdownVirus replicationNsp14 proteinGlobal health crisisProtein synthesisInhibition activityCausative agentCOVID-19COVID-19 pandemicSARS-CoV-2 nsp14Dependent inductionSingle-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replicationTranslational regulation of viral RNA in the type I interferon response
Hsu J, Laurent-Rolle M, Cresswell P. Translational regulation of viral RNA in the type I interferon response. Current Research In Virological Science 2021, 2: 100012. DOI: 10.1016/j.crviro.2021.100012.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsInterferon-stimulated genesViral infectionViral replicationIFN-I responsesType I interferon responseAntigen-independent mannerInnate immune responseVariety of mechanismsI interferon responseImmune responseVirus life cycleInfectious organismsInterferon responseHost factorsInfectionFirst lineViral RNAViral proteinsType IViral translationCommon cellular responseMolecular mechanismsInhibitionCellular responsesTranslation inhibition
2020
Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study
Wu A, Mihaylova VT, Landry ML, Foxman EF. Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study. The Lancet Microbe 2020, 1: e254-e262. PMID: 33103132, PMCID: PMC7580833, DOI: 10.1016/s2666-5247(20)30114-2.Peer-Reviewed Original ResearchConceptsRhinovirus infectionInterferon-stimulated genesExperimental infection studiesClinical data analysisMock infectionInfection studiesDay 3ISG expressionViral interferenceInterferon responsePrimary human airway epithelial culturesYale-New Haven HospitalHuman airway epithelial culturesIAV RNASeasonal influenza epidemicsNational InstituteAirway epithelial culturesReverse transcription-quantitative PCRTranscription-quantitative PCRElectronic medical record systemPeak virusAirway mucosaMedical record systemRespiratory virusesIAV infectionLung Atelectasis Promotes Immune and Barrier Dysfunction as Revealed by Transcriptome Sequencing in Female Sheep.
Zeng C, Motta-Ribeiro G, Hinoshita T, Lessa M, Winkler T, Grogg K, Kingston N, Hutchinson J, Sholl L, Fang X, Varelas X, Layne M, Baron R, Vidal Melo M. Lung Atelectasis Promotes Immune and Barrier Dysfunction as Revealed by Transcriptome Sequencing in Female Sheep. Anesthesiology 2020, 133: 1060-1076. PMID: 32796202, PMCID: PMC7572680, DOI: 10.1097/aln.0000000000003491.Peer-Reviewed Original ResearchConceptsAlveolar-capillary barrier functionInterferon-stimulated genesImmune responseLung atelectasisAerated lungBarrier functionAerated lung regionsPulmonary transcriptomeSystemic lipopolysaccharideYes-associated protein signalingPulmonary atelectasisGene Set Enrichment AnalysisSystemic inflammationBronchial blockerLung injuryRight lungBarrier dysfunctionComputed tomographyLipopolysaccharide exposureAtelectasisLipopolysaccharide infusionAbsolute fold changeYes-Associated ProteinAtelectatic lungLung
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