2025
Mapping pesticide-induced metabolic alterations in human gut bacteria
Chen L, Yan H, Di S, Guo C, Zhang H, Zhang S, Gold A, Wang Y, Hu M, Wu D, Johnson C, Wang X, Zhu J. Mapping pesticide-induced metabolic alterations in human gut bacteria. Nature Communications 2025, 16: 4355. PMID: 40348778, PMCID: PMC12065874, DOI: 10.1038/s41467-025-59747-6.Peer-Reviewed Original ResearchConceptsModulating gut microbiota compositionGut bacteria speciesGut microbial speciesHuman gut bacteriaGut microbiota compositionGut bacterial metabolismPesticide exposureHost healthGut bacteriaMicrobiota compositionMicrobial speciesBacterial metabolismBacteria speciesMolecular mechanismsComprehensive atlasLipid metabolismGutIn vivo mouse modelPesticidesHostMetabolismSpeciesInteractive atlasMouse modelMetabolic changesRecommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models.
Daugherty A, Milewicz D, Dichek D, Ghaghada K, Humphrey J, LeMaire S, Li Y, Mallat Z, Saeys Y, Sawada H, Shen Y, Suzuki T, Zhou Z. Recommendations for Design, Execution, and Reporting of Studies on Experimental Thoracic Aortopathy in Preclinical Models. Arteriosclerosis Thrombosis And Vascular Biology 2025 PMID: 40079138, DOI: 10.1161/atvbaha.124.320259.Peer-Reviewed Original ResearchEngineering Mice to Study Human Immunity.
Sefik E, Xiao T, Chiorazzi M, Odell I, Zhang F, Agrawal K, Micevic G, Flavell R. Engineering Mice to Study Human Immunity. Annual Review Of Immunology 2025 PMID: 40020225, DOI: 10.1146/annurev-immunol-082523-124415.Peer-Reviewed Original ResearchHumanized miceHuman hematopoiesisImmune responseImmune systemHumanized mouse modelHuman hematopoietic stemImmunocompromised murine hostsResident immune cellsHuman immune responseStudy human immunityHuman immune systemIntegration of multi-omicsHematopoietic stemImmune cell growthImmune cellsEngineered miceProgenitor cellsMouse modelImmunological diseasesMurine hostCancer treatmentPreclinical drugsHuman immunityMiceModel diseaseFAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma
Lubrano S, Cervantes-Villagrana R, Faraji F, Ramirez S, Sato K, Adame-Garcia S, Officer A, Arang N, Rigiracciolo D, Anguiano Quiroz P, Martini C, Wang Y, Ferguson F, Bacchiocchi A, Halaban R, Coma S, Holmen S, Pachter J, Aplin A, Gutkind J. FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma. Cancer Cell 2025, 43: 428-445.e6. PMID: 40020669, PMCID: PMC11903146, DOI: 10.1016/j.ccell.2025.02.001.Peer-Reviewed Original ResearchConceptsBRAF V600E melanomaFocal adhesion kinaseV600E melanomaFAK inhibitorActivated focal adhesion kinaseFocal adhesion kinase inhibitionRaf-MEKActivation of focal adhesion signalingFocal adhesion kinase inhibitorResistance to BRAFiSyngeneic mouse modelMAPK pathway inhibitionFocal adhesion signalingPro-apoptotic activityMelanoma patientsAdhesion signalingImmune therapyBRAF mutationsBRAFiTranscriptome analysisMelanomaMouse modelPathway inhibitionBRAFMelanoma cellsTumorigenesis Driven by BRAFV600E Requires Secondary Mutations that Overcome it's Feedback Inhibition of RAC1 and Migration.
Gadal S, Boyer J, Roy S, Outmezguine N, Sharma M, Li H, Fan N, Chan E, Romin Y, Barlas A, Chang Q, Pancholi P, Timaul N, Overholtzer M, Yaeger R, Manova-Todorova K, de Stanchina E, Bosenberg M, Rosen N. Tumorigenesis Driven by BRAFV600E Requires Secondary Mutations that Overcome it's Feedback Inhibition of RAC1 and Migration. Cancer Research 2025 PMID: 39992718, DOI: 10.1158/0008-5472.can-24-2220.Peer-Reviewed Original ResearchInhibition of Rac1Rac1 activationLevels of ERK activationSecondary mutationsBRAFV600E mutationInhibition of Rac1 activityMutant Rac1Cell motilityRac1ERK activationMesenchymal migrationFeedback inhibitionRestored migrationMutationsGenetically engineered mouse modelsCell proliferationSelection of lesionsTumor evolutionPTEN inactivationTumorigenesisOncogenic driversBRAFV600EMalignant transformationBenign neviMouse modelCCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models
Leser F, Júnyor F, Pagnoncelli I, Delgado A, Medeiros I, Nóbrega A, Andrade B, de Lima M, da Silva N, Jacob L, Boyé K, Geraldo L, de Souza A, Maron-Gutierrez T, Castro-Faria-Neto H, Follmer C, Braga C, Neves G, Eichmann A, Romão L, Lima F. CCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson’s disease models. Journal Of Neuroinflammation 2025, 22: 31. PMID: 39894839, PMCID: PMC11789347, DOI: 10.1186/s12974-024-03318-x.Peer-Reviewed Original ResearchConceptsMouse model of PDModel of PDMouse modelDopaminergic neuronsNeuron-microglia communicationNeuron-glia communicationParkinson's diseaseCCR7-dependent mannerMicroglial cell activationCCR7 expressionCCL21-CCR7Progressive degenerative diseaseCCR7 receptorMicroglial cell migrationInflammatory profileChemokine CCL21Cell activationCCL21Therapeutic strategiesChemokine inhibitorsTherapeutic implicationsMicroglial activationReceptor pathwayCCR7Behavioral deficitsParadoxical control of multifocal mammary oncogenesis by radiation therapy
Galluzzi L, Buqué A. Paradoxical control of multifocal mammary oncogenesis by radiation therapy. OncoImmunology 2025, 14: 2458886. PMID: 39873285, PMCID: PMC11776481, DOI: 10.1080/2162402x.2025.2458886.Peer-Reviewed Original ResearchAtgl-dependent adipocyte lipolysis promotes lipodystrophy and restrains fibrogenic responses during skin fibrosis
Caves E, Jussila A, Forni M, Benvie A, Lei V, King D, Edelman H, Hamdan M, Odell I, Hinchcliff M, Atit R, Horsley V. Atgl-dependent adipocyte lipolysis promotes lipodystrophy and restrains fibrogenic responses during skin fibrosis. Journal Of Investigative Dermatology 2025 PMID: 39884454, DOI: 10.1016/j.jid.2024.12.022.Peer-Reviewed Original ResearchLipid storageAdipocyte lipolysisExtracellular matrix proteinsFatty acidsTranscriptional analysisSkin fibrosisAdipocyte lipid storageTranscriptional changesSkin fibrosis developmentExtracellular matrix remodelingFibrosis developmentLipid-filled adipocytesDermal extracellular matrixHuman diseasesTreating fibrotic diseasesMouse modelMatrix proteinsDermal adipocytesFibrogenic responseGenetic modelsExtracellular matrixAdipocytesLoss of adipose tissueBleomycin-treated miceFibrotic mouse modelThe fungal microbiota modulate neonatal oxygen-induced lung injury
Martin I, Silverberg M, Abdelgawad A, Tanaka K, Halloran B, Nicola T, Myers E, Desai J, White C, Karabayir I, Akbilgic O, Tipton L, Gentle S, Ambalavanan N, Peters B, Vu L, Jain V, Lal C, Cormier S, Pierre J, Jilling T, Talati A, Willis K. The fungal microbiota modulate neonatal oxygen-induced lung injury. Microbiome 2025, 13: 24. PMID: 39871397, PMCID: PMC11773857, DOI: 10.1186/s40168-025-02032-x.Peer-Reviewed Original ResearchConceptsBronchopulmonary dysplasiaLung injury severityLung injuryDevelopment of bronchopulmonary dysplasiaSeverity of lung injuryAugmented lung injuryMorbidities of prematurityVery preterm infantsOxygen-induced lung injuryChronic lung diseaseIntestinal microbiomeMicrobiome of infantsPotential therapeutic strategyPreterm infantsNeonatal microbiomePremature infantsPremature neonatesInjury severityMurine modelNeonatal healthLung diseaseMouse modelTherapeutic strategiesLoss of function approachesFungal communitiesPharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage
Schlosser A, Pilecki B, Allen C, Benest A, Lynch A, Hua J, Ved N, Blackley Z, Andersen T, Hennig D, Graversen J, Möller S, Skallerup S, Ormhøj M, Lange C, Agostini H, Grauslund J, Heegaard S, Dacheva I, Koss M, Hu W, Iglesias B, Lawrence M, Beck H, Steffensen L, Laursen N, Andersen G, Holmskov U, Bates D, Sorensen G. Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage. Molecular Therapy 2025, 33: 1048-1072. PMID: 39863929, PMCID: PMC11897753, DOI: 10.1016/j.ymthe.2025.01.038.Peer-Reviewed Original ResearchConceptsMicrofibrillar-associated protein 4Vascular leakageNeovascular age-related macular degenerationAge-related macular degenerationChoroidal neovascularization mouse modelDiabetic macular edemaProtein 4Treatment of neovascularizationLaser-induced choroidal neovascularization mouse modelVascular leakage areaDuration of efficacyVascular endothelial cellsRetinal neoangiogenesisMacular edemaRetinal neovascularizationMacular degenerationVision lossRetinal diseasesPharmacological blockMuller cellsRetinal astrocytesVascular permeabilityVascular mural cellsEndothelial cell motilityMouse modelMicroglia modulate the cerebrovascular reactivity through ectonucleotidase CD39
Fu Z, Ganesana M, Hwang P, Tan X, Kinkaid M, Sun Y, Bian E, Weybright A, Chen H, Sol-Church K, Eyo U, Pridans C, Quintana F, Robson S, Kumar P, Venton B, Schaefer A, Kuan C. Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39. Nature Communications 2025, 16: 956. PMID: 39843911, PMCID: PMC11754601, DOI: 10.1038/s41467-025-56093-5.Peer-Reviewed Original ResearchConceptsCerebral blood flowEctonucleotidases CD39Whisker stimulationResponse to whisker stimulationCerebrovascular reactivityDeletion of CD39Blood flowInjection of adenosine triphosphateModulation of cerebral blood flowRegulation of cerebral blood flowExtracellular adenosine triphosphateInjection of adenosineBorder-associated macrophagesMicroglia repopulationExtracellular adenosineAdenosine triphosphateFemale miceBlood flow anomaliesP2RY12 receptorCo-transmitterMouse modelPharmacological inhibitionCD39MicrogliaMiceType 2 immunity to the rescue: enhancing antitumor immunity for skin cancer prevention
Vesely M, Christensen S. Type 2 immunity to the rescue: enhancing antitumor immunity for skin cancer prevention. Journal Of Clinical Investigation 2025, 135: e188018. PMID: 39744952, PMCID: PMC11684797, DOI: 10.1172/jci188018.Peer-Reviewed Original ResearchConceptsCutaneous squamous cell carcinomaThymic stromal lymphopoietinType 2 immunityActinic keratosisAK lesionsTh2 cellsPrevent cutaneous squamous cell carcinomaRecruitment of Th2 cellsCSCC preventionSquamous cell carcinomaMouse model of skin carcinogenesisModel of skin carcinogenesisDamage-associated molecular patternsKeratinocyte cell deathAntitumor immunityTopical calcipotriolSkin cancer preventionCell carcinomaPaired biopsiesPrecursor lesionsSkin carcinogenesisUnaffected skinMouse modelCancer preventionPremalignant keratinocytesOlanzapine Induces Adipogenesis and Glucose Uptake by Activating Glycolysis and Synergizing with the PI3K-AKT Pathway
Li S, Fu Y, Wang W, Qiu J, Huang Y, Li X, Yang K, Yu X, Ma Y, Zhang Y, Zhang M, Li J, Li W. Olanzapine Induces Adipogenesis and Glucose Uptake by Activating Glycolysis and Synergizing with the PI3K-AKT Pathway. Current Neuropharmacology 2025, 23: 412-425. PMID: 39150031, DOI: 10.2174/1570159x22666240815120547.Peer-Reviewed Original ResearchAdministration of olanzapineTreated with olanzapineReactive oxygen speciesDownstream PI3K-Akt signal pathwayAssociated with obesityActive glycolysisAssessed body weightWeight gainDifferentiated 3T3-L1 preadipocytesLiver fat levelsPI3K-Akt pathwayOlanzapineDrug doseFemale miceDietary patternsMetabolic markersPI3K-AktFood intakeGlucose uptakeMouse modelGlycolipid abnormalitiesRodent modelsBody weightGAPDH expressionSignaling pathway
2024
Heterogeneous Cardiac-Derived and Neural Crest–Derived Aortic Smooth Muscle Cells Exhibit Similar Transcriptional Changes After TGFβ Signaling Disruption
Ren P, Jiang B, Hassab A, Li G, Li W, Assi R, Tellides G. Heterogeneous Cardiac-Derived and Neural Crest–Derived Aortic Smooth Muscle Cells Exhibit Similar Transcriptional Changes After TGFβ Signaling Disruption. Arteriosclerosis Thrombosis And Vascular Biology 2024, 45: 260-276. PMID: 39697172, DOI: 10.1161/atvbaha.124.321706.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic AneurysmCell LineageDisease Models, AnimalGene Expression ProfilingHomeobox Protein Nkx-2.5HumansMaleMarfan SyndromeMiceMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleMyosin Heavy ChainsNeural CrestPhenotypeReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSignal TransductionSingle-Cell AnalysisTranscription, GeneticTranscriptomeTransforming Growth Factor betaWnt1 ProteinConceptsSmooth muscle cell clustersSmooth muscle cellsAortic smooth muscle cellsNeural crest-derived smooth muscle cellsCardiac derivativesMurine aortic smooth muscle cellsNeural crest originReceptor deletionAortic rootAdult miceNeural crest progenitorsNKX2-5Proximal aortaTranscriptional changesMouse modelTGFB signalingMuscle cellsConditional deletionAdult human aortaEmbryological originIncreased expressionAnalyzed single-cell transcriptomesTGFB receptorsBasal stateAortic homeostasisImpact of radiation therapy dose, fractionation, and immunotherapeutic partner in a mouse model of hormone receptor–positive mammary carcinogenesis
Buqué A, Bloy N, Petroni G, Jiménez-Cortegana C, Sato A, Iribarren C, Yamazaki T, Galassi C, Hensler M, Bhinder B, Guarracino A, Rippon B, Beltran-Visiedo M, Soler-Agesta R, Pannellini T, Fucikova J, Demaria S, Zhou X, Elemento O, Formenti S, Galluzzi L. Impact of radiation therapy dose, fractionation, and immunotherapeutic partner in a mouse model of hormone receptor–positive mammary carcinogenesis. Journal Of The National Cancer Institute 2024, djae329. PMID: 39661487, DOI: 10.1093/jnci/djae329.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRadiation therapyFocal RTOverall survivalMammary carcinogenesisPD-1Impact of radiotherapy doseMouse modelPD-1 blockerRT plus immunotherapyPrimary tumor growthPrimary disease controlIncrease local controlCheckpoint inhibitorsRadiotherapy doseHypofractionated RTOS benefitTumor burdenPrimary tumorBreast cancerTumor growthNeoplastic lesionsLocal controlICI sensitivityEffective immunitySlow and fast cortical cholinergic arousal is reduced in a mouse model of focal seizures with impaired consciousness
Sieu L, Singla S, Liu J, Zheng X, Sharafeldin A, Chandrasekaran G, Valcarce-Aspegren M, Niknahad A, Fu I, Doilicho N, Gummadavelli A, McCafferty C, Crouse R, Perrenoud Q, Picciotto M, Cardin J, Blumenfeld H. Slow and fast cortical cholinergic arousal is reduced in a mouse model of focal seizures with impaired consciousness. Cell Reports 2024, 43: 115012. PMID: 39643969, PMCID: PMC11817788, DOI: 10.1016/j.celrep.2024.115012.Peer-Reviewed Original ResearchCortical slow wavesFocal seizuresBehavioral responsesAuditory stimuliImpaired behavioral responsesFocal temporal lobe seizuresImpaired consciousnessMouse modelAwake mouse modelResponses to auditory stimuliBehavioral responses to auditory stimuliDecreased cortical arousalImpaired behaviorSlow wavesTemporal lobe seizuresCholinergic releaseModel of focal seizuresHigh-frequency activityCortical functionCortical arousalDepressed cortical functionSubcortical arousalArousalAcetylcholine releaseRat modelEzrin drives adaptation of monocytes to the inflamed lung microenvironment
Gudneppanavar R, Di Pietro C, H Öz H, Zhang P, Cheng E, Huang P, Tebaldi T, Biancon G, Halene S, Hoppe A, Kim C, Gonzalez A, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. Cell Death & Disease 2024, 15: 864. PMID: 39613751, PMCID: PMC11607083, DOI: 10.1038/s41419-024-07255-8.Peer-Reviewed Original ResearchConceptsActivation of focal adhesion kinaseExtracellular matrixActin-binding proteinsFocal adhesion kinaseLung extracellular matrixKnock-out mouse modelProtein kinase signalingCortical cytoskeletonLoss of ezrinKinase signalingPlasma membraneCell migrationSignaling pathwayEzrinResponse to lipopolysaccharideTissue-resident macrophagesMouse modelLipopolysaccharideCytoskeletonEzrin expressionLung microenvironmentKinaseMonocyte recruitmentProteinAktMouse Models Enable the Functional Investigation of Tertiary Lymphoid Structures in Cancer
Jeevanandam A, Yin Z, Connolly K, Joshi N. Mouse Models Enable the Functional Investigation of Tertiary Lymphoid Structures in Cancer. Methods In Molecular Biology 2024, 2864: 57-76. PMID: 39527217, DOI: 10.1007/978-1-0716-4184-2_4.Peer-Reviewed Original ResearchConceptsTertiary lymphoid structuresTertiary lymphoid structure formationSecondary lymphoid organsLymphoid structuresMurine modelFeatures of tertiary lymphoid structuresFunction of tertiary lymphoid structuresMouse modelPersistent inflammatory stimulationAssociated with positive clinical outcomesTissue-specific regulatory mechanismsPositive clinical outcomesPrognostic significanceClinical outcomesGut environmentNonlymphoid tissuesLymphoid aggregatesLymphoid organsMouse lungCancer patientsGenetic sequencesInflammatory stimulationRegulatory mechanismsTherapeutic modulationClinical effortsEfficient and selective kidney targeting by chemically modified carbohydrate conjugates
Kumar V, Wahane A, Tham M, Somlo S, Gupta A, Bahal R. Efficient and selective kidney targeting by chemically modified carbohydrate conjugates. Molecular Therapy 2024, 32: 4383-4400. PMID: 39532098, PMCID: PMC11638880, DOI: 10.1016/j.ymthe.2024.10.020.Peer-Reviewed Original ResearchProximal convoluted tubulesPeptide nucleic acidConvoluted tubulesNucleic acid analogsDecreased collagen depositionAntisense peptide nucleic acidFibrosis mouse modelCarbohydrate conjugatesKidney disease modelsSystemic deliveryFibrosis progressionSmall moleculesKidney cell lineAdverse reactionsMiR-33Mouse modelBiodistribution studiesImmunofluorescence stainingCollagen depositionKidney targetingTargeted deliveryLigandCell linesEndocytic uptakeAcid analogsMISTRG6kitW41: Enhanced Engraftment in a Cytokine Humanized Patient-Derived Xenotransplantation Mouse Model
Baassiri A, Maziarz J, Blackburn H, Maul-Newby H, VanOudenhove J, Zhang X, Matthews M, Paul S, Liu W, Sefik E, Salomonis N, Grimes H, Flavell R, Halene S. MISTRG6kitW41: Enhanced Engraftment in a Cytokine Humanized Patient-Derived Xenotransplantation Mouse Model. Blood 2024, 144: 1815-1815. DOI: 10.1182/blood-2024-211908.Peer-Reviewed Original ResearchPeripheral blood-mobilized stem cellsAcute myeloid leukemiaProgression to secondary acute myeloid leukemiaHematopoietic stem cellsWeeks post-engraftmentSecondary acute myeloid leukemiaStudies of myelodysplastic syndromesMyelodysplastic syndromeCD34+ cellsEngraftment levelsPeripheral bloodBone marrowK micePost-engraftmentMouse modelNSG miceMDS samplesEngraftment of human hematopoietic stem cellsEnhanced engraftmentProgression to acute myeloid leukemiaHealthy donor peripheral bloodHuman CD45+ cellsHuman hematopoietic stem cellsAnalysis of CD34+ cellsPercentage of lymphoid cells
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