2025
The first-in-human phase 1/2 study of TSN1611, a highly selective KRAS G12D inhibitor, in patients with advanced solid tumors.
Fu S, Shen L, Lu S, Sommerhalder D, Liu T, Spira A, Li J, Yu Y, Li W, Li J, Song B, Dong C, Lai L, Ma S, Shang E, Zhong B, Zhang T. The first-in-human phase 1/2 study of TSN1611, a highly selective KRAS G12D inhibitor, in patients with advanced solid tumors. Journal Of Clinical Oncology 2025, 43: 3083-3083. DOI: 10.1200/jco.2025.43.16_suppl.3083.Peer-Reviewed Original ResearchMaximum tolerated doseNon-small cell lung cancer modelTreatment related adverse eventsPancreatic ductal carcinomaColorectal cancerSolid tumorsFirst-in-human phase 1/2 studyRecommended phase 2 doseTumor cells in vitroMedian prior linesPhase 1/2 studyPhase 1b/2 studyPhase 2 dosePhase 2 partRelated grade 3Dose-limiting toxicityAdvanced solid tumorsDose-escalation partEvaluated dose rangeNausea and diarrheaInhibited tumor growthLung cancer modelRelated adverse eventsStandard of careCells in vitroInvestigation of the protein corona and biodistribution profile of polymeric nanoparticles for intra-amniotic delivery
Lynn A, Shin K, Eaton D, Rose M, Zhang X, Ene M, Grundler J, Deschenes E, Rivero R, Bracaglia L, Glazer P, Stitelman D, Saltzman W. Investigation of the protein corona and biodistribution profile of polymeric nanoparticles for intra-amniotic delivery. Biomaterials 2025, 320: 123238. PMID: 40064138, PMCID: PMC11972154, DOI: 10.1016/j.biomaterials.2025.123238.Peer-Reviewed Original ResearchAmniotic fluidProtein corona formationProtein coronaIntra-amniotic deliveryNP delivery systemPEGylated nanoparticlesSurface polyethylene glycolPoly(lactic-co-glycolic acidProtein corona compositionLung cells in vitroCorona formationPLA-PEG nanoparticlesNon-PEGylated nanoparticlesCells in vitroLevels of albuminFetal bowelFetal lungFetal organsNP biodistributionPoly(lactic-acidDense brush conformationCorona compositionPolyvinyl alcoholBiodistribution profileCellular associationExploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma
Yang L, Pham K, Xi Y, Wu Q, Liu D, Robertson K, Liu C. Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma. PLOS ONE 2025, 20: e0317401. PMID: 39841705, PMCID: PMC11753693, DOI: 10.1371/journal.pone.0317401.Peer-Reviewed Original ResearchConceptsGlypican-3Hepatocellular carcinomaCAR-NKNatural killerCell linesCAR-NK therapyCAR-NK cellsTreatment of hepatocellular carcinomaNK cell lineAnti-tumor effectsCancer-related mortalitySuppressed tumor growthPrimary liver cancerInfluence therapeutic outcomesCells in vitroHepatocellular carcinoma treatmentHepG2 cells in vitroNK92MI cellsImmunotherapy strategiesNSG miceImmunotherapy targetOncofetal glycoproteinTherapy resistanceImprove patient outcomesPoor prognosis
2024
A framework for neural organoids, assembloids and transplantation studies
Pașca S, Arlotta P, Bateup H, Camp J, Cappello S, Gage F, Knoblich J, Kriegstein A, Lancaster M, Ming G, Novarino G, Okano H, Parmar M, Park I, Reiner O, Song H, Studer L, Takahashi J, Temple S, Testa G, Treutlein B, Vaccarino F, Vanderhaeghen P, Young-Pearse T. A framework for neural organoids, assembloids and transplantation studies. Nature 2024, 639: 315-320. PMID: 39653126, DOI: 10.1038/s41586-024-08487-6.Peer-Reviewed Original ResearchNovel immunotherapeutics against LGR5 to target multiple cancer types
Chen H, Mueller N, Stott K, Kapeni C, Rivers E, Sauer C, Beke F, Walsh S, Ashman N, O’Brien L, Rafati Fard A, Ghodsinia A, Li C, Joud F, Giger O, Zlobec I, Olan I, Aitken S, Hoare M, Mair R, Serrao E, Brenton J, Garcia-Gimenez A, Richardson S, Huntly B, Spring D, Skjoedt M, Skjødt K, de la Roche M, de la Roche M. Novel immunotherapeutics against LGR5 to target multiple cancer types. EMBO Molecular Medicine 2024, 16: 2233-2261. PMID: 39169164, PMCID: PMC11393416, DOI: 10.1038/s44321-024-00121-2.Peer-Reviewed Original ResearchConceptsHepatocellular carcinomaColorectal cancerTarget multiple cancer typesBispecific T-cell engagerCell killing in vitroChimeric antigen receptorT-cell engagersCancer cells in vitroPre-B-ALLAnti-tumor efficacyCancer cell killing in vitroKilling in vitroCells in vitroAntibody-drug conjugatesMultiple cancer typesLgr5 overexpressionTumor burdenAntigen receptorMurine modelNovel immunotherapeuticsCancer modelsTumor cellsEffective modalityEffective tumorLgr5Lipocoacervate, a tunable vesicle for protein delivery
Yeh C, Wright N, Loh C, Chu N, Wang Y. Lipocoacervate, a tunable vesicle for protein delivery. Nano Research 2024, 17: 9135-9140. DOI: 10.1007/s12274-024-6889-6.Peer-Reviewed Original ResearchProtein delivery vehiclesDelivery of proteinsCells in vitroGrowth factorVesiclesProteinMembrane functionControlled delivery of growth factorsTreated cells in vitroProtein deliveryControlled deliveryControlled delivery of proteinsDelivery of therapeuticsSalt concentrationDelivery of growth factorsMembraneVesicle sizeControlled delivery of therapeuticsBACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells
Thakore P, Schnell A, Huang L, Zhao M, Hou Y, Christian E, Zaghouani S, Wang C, Singh V, Singaraju A, Krishnan R, Kozoriz D, Ma S, Sankar V, Notarbartolo S, Buenrostro J, Sallusto F, Patsopoulos N, Rozenblatt-Rosen O, Kuchroo V, Regev A. BACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells. Nature Immunology 2024, 25: 1395-1410. PMID: 39009838, DOI: 10.1038/s41590-024-01901-1.Peer-Reviewed Original ResearchConceptsTransposase-accessible chromatin sequencingSingle-cell RNA sequencingTh17 heterogeneitySingle-cell assaysScATAC-seqChromatin landscapeChromatin stateChromatin sequencingRegulatory networksScRNA-seqTh17 cell pathogenicityHuman geneticsIn vivoRNA sequencingChromatin configurationRegulatory pathwaysTissue homeostasisCell statesCells in vitroBach2ChromatinSequenceCellsType 1 helper T (Th1) cellsCD4+ T cell subsetsPreclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma
McNamara B, Greenman M, Bellone S, Santin L, Demirkiran C, Mutlu L, Hartwich T, Yang-Hartwich Y, Ratner E, Schwartz P, Santin A. Preclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma. Gynecologic Oncology 2024, 189: 16-23. PMID: 38981151, DOI: 10.1016/j.ygyno.2024.07.002.Peer-Reviewed Original ResearchTargets trophoblast cell-surface antigen-2Epithelial ovarian cancerAntibody-dependent cellular cytotoxicityPreclinical activityAntibody drug conjugatesOvarian cancerCell linesTumor cellsTrophoblast cell surface antigen 2Cell line-derived xenograft modelFlow cytometryCompared to tumor cellsEpithelial ovarian cancer cell linesOvarian cancer cell linesTumor cells in vitroOvarian cancer patientsPeripheral-blood lymphocytesEOC cell linesTumor growth suppressionAnnexin V-positiveGynecologic cancer mortalityIn vivo antitumor activityCells in vitroPrimary cell linesUnmet medical needLiver Sinusoidal Endothelial Cells Contribute to Portal Hypertension Through Collagen Type IV–Driven Sinusoidal Remodeling
Gan C, Yaqoob U, Lu J, Xie M, Anwar A, Jalan-Sakrikar N, Jerez S, Sehrawat T, Navarro-Corcuera A, Kostallari E, Habash N, Cao S, Shah V. Liver Sinusoidal Endothelial Cells Contribute to Portal Hypertension Through Collagen Type IV–Driven Sinusoidal Remodeling. JCI Insight 2024, 9: e174775. PMID: 38713515, PMCID: PMC11382879, DOI: 10.1172/jci.insight.174775.Peer-Reviewed Original ResearchLiver sinusoidal endothelial cellsPortal hypertensionSinusoidal remodelingSinusoidal endothelial cellsSinusoidal resistanceComplication of liver cirrhosisEndothelial cellsSinusoidal endothelial cells in vitroEnhancer-promoter interactionsEpigenome editing approachesEndothelial cells in vitroChronic liver injuryCells in vitroMouse fibrotic liversCollagen type IVLiver cirrhosisGene mutationsExpression regulationLiver fibrosisLiver injuryEpigenetic repressionLiver diseaseCellular sourceCol4 expressionImmunofluorescence stainingDOCK8 and STAT3 cooperate to restrain IgE-inducing T follicular helper cells.
Williams A, Siniscalco E, Grassmann J, Craft J, Eisenbarth S, Uthaman G. DOCK8 and STAT3 cooperate to restrain IgE-inducing T follicular helper cells. The Journal Of Immunology 2024, 212: 0620_4120-0620_4120. DOI: 10.4049/jimmunol.212.supp.0620.4120.Peer-Reviewed Original ResearchPeanut-specific IgET cellsSpecific IgEFood allergyT follicular helper cellsCD4+ T cellsDOCK8-deficient patientsFood-specific IgEPeanut-specific IgE.Human T cellsCells in vitroDifferentiation in vivoSevere food allergyTfh cellsRegulatory populationsOvercome toleranceHelper cellsDeficient patientsSpecific IgE.DOCK8IgE productionSTAT3 mutationsMiceCholera toxinIgEA 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
2022
Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells
North K, Benbarche S, Liu B, Pangallo J, Chen S, Stahl M, Bewersdorf J, Stanley R, Erickson C, Cho H, Pineda J, Thomas J, Polaski J, Belleville A, Gabel A, Udy D, Humbert O, Kiem H, Abdel-Wahab O, Bradley R. Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells. Nature Biotechnology 2022, 40: 1103-1113. PMID: 35241838, PMCID: PMC9288984, DOI: 10.1038/s41587-022-01224-2.Peer-Reviewed Original ResearchConceptsBreast cancerExpression of herpes simplex virus thymidine kinaseHerpes simplex virus thymidine kinaseCancer cellsPancreatic cancer cells in vitroWild-type cellsCancer cells in vitroCancer gene therapyTargeting of cancer cellsTumor-specific changesUveal melanoma cellsTreatment in vivoSynthetic intronChange-of-function mutationsCells in vitroUveal melanomaSF3B1 mutationsHSV-tkGene therapyTumor cellsIsogenic wild-type cellsMelanoma cellsRNA splicing factorsCancerHost survival
2017
FGF9 prevents pleural fibrosis induced by intrapleural adenovirus injection in mice
Justet A, Joannes A, Besnard V, Marchal-Sommé J, Jaillet M, Bonniaud P, Sallenave J, Solhonne B, Castier Y, Mordant P, Mal H, Cazes A, Borie R, Mailleux A, Crestani B. FGF9 prevents pleural fibrosis induced by intrapleural adenovirus injection in mice. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2017, 313: l781-l795. PMID: 28729349, DOI: 10.1152/ajplung.00508.2016.Peer-Reviewed Original ResearchConceptsFibroblast growth factor 9FGF9 overexpressionMesothelial cellsExpression of fibroblast growth factor 9Pleural thickeningMyofibroblast differentiationDay 5</i>Mesothelial cells in vivoFetal lung developmentMesothelial cells in vitroHuman idiopathic pulmonary fibrosisA-smooth muscle actinIdiopathic pulmonary fibrosisMarkers of inflammationDay 3</i>Effects of fibroblast growth factor 9In vitroInjury in vivoRat mesothelial cellsCells in vitroCells in vivoDiffuse pleural thickeningMesothelial cell migrationFGF receptorsAdenovirus injection10 Noninvasive optical imaging of stem cell differentiation in biomaterials using photonic crystal surfaces
Choi J, Zhuo Y, Cunningham B, Harley B. 10 Noninvasive optical imaging of stem cell differentiation in biomaterials using photonic crystal surfaces. 2017, 195-207. DOI: 10.1016/b978-0-08-100603-0.00010-9.Peer-Reviewed Original ResearchPhotonic crystal surfacePlastic substratesStem cell differentiationReal timeImaging of stem cellsStem cell fate decisionsCell differentiationCell fate decisionsCell differentiation eventsLabel-free imaging of live cellsCells in vitroNoninvasive optical imagingCrystal surfacePopulations in situLiving cells in vitroSingle-cell levelPhotonic crystalsFate decisionsOrdinary glassSurfaceLabel-free imagingPool of cellsBioengineered platformCell growthPopulation of cells
2014
EGFR, HER2 and HER3 dimerization patterns guide targeted inhibition in two histotypes of esophageal cancer
Fichter C, Timme S, Braun J, Gudernatsch V, Schöpflin A, Bogatyreva L, Geddert H, Faller G, Klimstra D, Tang L, Hauschke D, Werner M, Lassmann S. EGFR, HER2 and HER3 dimerization patterns guide targeted inhibition in two histotypes of esophageal cancer. International Journal Of Cancer 2014, 135: 1517-1530. PMID: 24510732, DOI: 10.1002/ijc.28771.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAntibodies, Monoclonal, HumanizedAntibody-Dependent Cell CytotoxicityApoptosisBlotting, WesternCarcinoma, Squamous CellCell Cycle CheckpointsCell ProliferationErbB ReceptorsErlotinib HydrochlorideEsophageal NeoplasmsFluorescent Antibody TechniqueGefitinibGene Expression Regulation, NeoplasticHumansImmunoenzyme TechniquesProtein Kinase InhibitorsProtein MultimerizationQuinazolinesReceptor, ErbB-2Receptor, ErbB-3Tumor Cells, CulturedConceptsEsophageal squamous cell carcinomaReceptor tyrosine kinasesEAC casesInduce antibody-dependent cellular cytotoxicityEAC cells in vitroAntibody-dependent cellular cytotoxicityEAC cellsPeripheral blood mononuclear cellsResponse to erlotinibSquamous cell carcinomaHER2-targeted antibodiesCancer in situBlood mononuclear cellsLoss of Akt phosphorylationOverexpression of EGFRCells in vitroResponse to EGFRInduction of apoptosisG0/G1 cell cycle arrestHER3 expressionHER2-positiveCell cycle arrestEpithelial tumorsEsophageal carcinomaCell carcinoma
2013
A Special Population of Regulatory T Cells Potentiates Muscle Repair
Burzyn D, Kuswanto W, Kolodin D, Shadrach J, Cerletti M, Jang Y, Sefik E, Tan T, Wagers A, Benoist C, Mathis D. A Special Population of Regulatory T Cells Potentiates Muscle Repair. Cell 2013, 155: 1282-1295. PMID: 24315098, PMCID: PMC3894749, DOI: 10.1016/j.cell.2013.10.054.Peer-Reviewed Original ResearchConceptsTreg cellsMuscle repairDepletion of Treg cellsPopulation of Treg cellsSuppressors of immune responsesMuscle repair in vivoMyeloid lineage cellsGrowth factor amphiregulinSatellite cells in vitroImpaired muscle repairCells in vitroGenetically dystrophic miceProinflammatory infiltratesSkeletal muscle of miceMuscle of miceTreg activityTreg populationDystrophic miceImmune responseMuscular dystrophyTherapeutic opportunitiesNonimmunologic processesTregsWound repairMuscle damageReversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer
Siddle H, Kreiss A, Tovar C, Yuen C, Cheng Y, Belov K, Swift K, Pearse A, Hamede R, Jones M, Skjødt K, Woods G, Kaufman J. Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 5103-5108. PMID: 23479617, PMCID: PMC3612627, DOI: 10.1073/pnas.1219920110.Peer-Reviewed Original ResearchConceptsDFTD cellsDown-regulation of MHC moleculesMHC class I moleculesClass I moleculesDevil facial tumour diseaseExpression of MHC class I moleculesI moleculesMHC moleculesTumor diseaseMHC class II transactivatorAssociated with up-regulationIn vivoClass II transactivatorTransporter associated with antigen processingLoss of gene expressionCells in vitroDown-regulationAntigen processing pathwayHost immune responseFacial tumour diseaseContagious cancerImmune escapeUnusual pathogenLymphocytic infiltrationT cells
2012
T helper 17 cell lineage commitment is dictated by DC populations resident in priming tissues (163.23)
Hu W, Troutman T, Pasare C. T helper 17 cell lineage commitment is dictated by DC populations resident in priming tissues (163.23). The Journal Of Immunology 2012, 188: 163.23-163.23. DOI: 10.4049/jimmunol.188.supp.163.23.Peer-Reviewed Original ResearchCD103+ dendritic cellsDendritic cellsTh17 lineage commitmentIL-6IL-1Th17 differentiationLineage commitmentDifferentiation of CD4 T cellsGeneration of iTreg cellsTh17 cells in vitroActivation of pattern recognition receptorsDifferentiation of Th17 cells in vitroTh1 lineage developmentCD103+ DCCD4 T cellsContribution of IL-6Mucosal immune systemIntestinal immune homeostasisSecretion of cytokinesIntestinal lamina propriaSite of primingCells in vitroRegulate Th17 differentiationPattern recognition receptorsITreg cells
2011
Sarcomas induced in discrete subsets of prospectively isolated skeletal muscle cells
Hettmer S, Liu J, Miller C, Lindsay M, Sparks C, Guertin D, Bronson R, Langenau D, Wagers A. Sarcomas induced in discrete subsets of prospectively isolated skeletal muscle cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 20002-20007. PMID: 22135462, PMCID: PMC3250188, DOI: 10.1073/pnas.1111733108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCell LineageCell ProliferationCell SeparationCell Transformation, NeoplasticGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunohistochemistryMiceMice, Inbred C57BLMuscle CellsMuscle DevelopmentMuscle Fibers, SkeletalMuscle NeoplasmsMuscle, Skeletalras ProteinsRatsSarcomaSignal TransductionTOR Serine-Threonine KinasesTranscriptomeConceptsMechanistic target of rapamycinRhabdomyosarcoma cells in vitroHuman rhabdomyosarcomaTumor cell of originKirsten rat sarcoma viral oncogeneCyclin-dependent kinase inhibitor 2AIsolated skeletal muscle cellsRat sarcoma viral oncogeneChimeric mouse modelSoft tissue sarcomasIsolated satellite cellsCell of originMechanistic target of rapamycin signalingCells in vitroGene expression signaturesMesenchymal cell lineagesConsistent with activationSkeletal muscle cellsMyogenic featuresTissue-specific differentiation markersPleomorphic rhabdomyosarcomaCluster of genesInhibition of RasTarget of rapamycinHeterogeneous cancer
2007
In vivo genetic profiling and cellular localization of apelin reveals a hypoxia-sensitive, endothelial-centered pathway activated in ischemic heart failure
Sheikh A, Chun H, Glassford A, Kundu R, Kutschka I, Ardigo D, Hendry S, Wagner R, Chen M, Ali Z, Yue P, Huynh D, Connolly A, Pelletier M, Tsao P, Robbins R, Quertermous T. In vivo genetic profiling and cellular localization of apelin reveals a hypoxia-sensitive, endothelial-centered pathway activated in ischemic heart failure. AJP Heart And Circulatory Physiology 2007, 294: h88-h98. PMID: 17906101, PMCID: PMC2570026, DOI: 10.1152/ajpheart.00935.2007.Peer-Reviewed Original ResearchMeSH KeywordsAdipokinesAnimalsApelinApelin ReceptorsBasic Helix-Loop-Helix Transcription FactorsCarrier ProteinsCell HypoxiaCells, CulturedCoronary VesselsDisease Models, AnimalEndothelial CellsFemaleGene Expression ProfilingGenes, ReporterHeart FailureHumansHypoxiaHypoxia-Inducible Factor 1, alpha SubunitIntercellular Signaling Peptides and ProteinsLac OperonLigationLungMiceMice, TransgenicMyocardial IschemiaMyocardiumPromoter Regions, GeneticQuadriceps MuscleReceptors, G-Protein-CoupledRNA, MessengerSignal TransductionTime FactorsTransfectionUp-RegulationConceptsApelin-APJ pathwayHeart failureCardiac failureApelin expressionCultured endothelial cells in vitroConditions associated with heart failureLocalization of apelinRegulation of cardiovascular functionG protein-coupled receptor APJIschemic heart failureIschemic cardiac failureSystemic vascular resistanceEndothelial cells in vitroLocal tissue hypoxiaSystemic hypoxic exposureNitric oxide-dependent signalingCells in vitroRegulating cardiovascular homeostasisVasopressin pathwayInotropic effectCardiac contractilityVascular resistanceMurine modelLigand apelinMyocardial injury
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply