2021
Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells
Song Y, Shan L, Gbyli R, Liu W, Strowig T, Patel A, Fu X, Wang X, Xu ML, Gao Y, Qin A, Bruscia EM, Tebaldi T, Biancon G, Mamillapalli P, Urbonas D, Eynon E, Gonzalez DG, Chen J, Krause DS, Alderman J, Halene S, Flavell RA. Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells. Science 2021, 371: 1019-1025. PMID: 33674488, PMCID: PMC8292008, DOI: 10.1126/science.abe2485.Peer-Reviewed Original ResearchConceptsRed blood cellsBlood cellsHuman sickle cell diseaseSickle cell diseaseImmunodeficient murine modelKupffer cell densityBone marrow failureMISTRG miceIntrasplenic injectionSCD pathologyCell diseaseMurine modelComplement C3RBC survivalVivo modelHuman cytokinesPreclinical testingHematopoietic stem cellsHuman red blood cellsMarrow failureFumarylacetoacetate hydrolase geneHuman erythropoiesisHuman liverHuman hepatocytesMice
2018
Surfactant protein C dampens inflammation by decreasing JAK/STAT activation during lung repair
Jin H, Ciechanowicz AK, Kaplan AR, Wang L, Zhang P, Lu YC, Tobin RE, Tobin BA, Cohn L, Zeiss CJ, Lee PJ, Bruscia EM, Krause DS. Surfactant protein C dampens inflammation by decreasing JAK/STAT activation during lung repair. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2018, 314: l882-l892. PMID: 29345196, PMCID: PMC6008135, DOI: 10.1152/ajplung.00418.2017.Peer-Reviewed Original ResearchConceptsAcute respiratory distress syndromeKO miceSurfactant protein CClinical acute respiratory distress syndromeProtein CAlveolar type 2 cellsAnti-inflammatory mediatorsRespiratory distress syndromeBronchoalveolar lavage fluidAnti-inflammatory moleculesPhosphorylated signal transductionType 2 cellsSPC expressionInducible suicide geneJanus kinaseLevels of suppressorDistress syndromeBAL fluidGranulocyte infiltrationJAK1/2 inhibitorLavage fluidProinflammatory phenotypeInflammatory cytokinesSevere inflammationInjury model
2017
Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages
Di Pietro C, Zhang PX, O’Rourke T, Murray TS, Wang L, Britto CJ, Koff JL, Krause DS, Egan ME, Bruscia EM. Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages. Scientific Reports 2017, 7: 10882. PMID: 28883468, PMCID: PMC5589856, DOI: 10.1038/s41598-017-11012-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorCytoskeletal ProteinsDisease Models, AnimalMacrophage ActivationMacrophagesMicePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPseudomonas aeruginosaPseudomonas InfectionsSignal TransductionToll-Like Receptor 4ConceptsCystic fibrosis transmembrane conductance regulatorPI3K/AktFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorPI3K/Akt signalingConductance regulatorAnti-bacterial immune responseAkt signalingAltered localizationEzrinCystic fibrosis diseaseMφ activationAktProtein levelsFibrosis diseaseActivationImmune regulationPhagocytosisInductionDirect linkSignalingRegulatorImmune responseMΦMacrophages
2016
In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery
Bahal R, Ali McNeer N, Quijano E, Liu Y, Sulkowski P, Turchick A, Lu YC, Bhunia DC, Manna A, Greiner DL, Brehm MA, Cheng CJ, López-Giráldez F, Ricciardi A, Beloor J, Krause DS, Kumar P, Gallagher PG, Braddock DT, Mark Saltzman W, Ly DH, Glazer PM. In vivo correction of anaemia in β-thalassemic mice by γPNA-mediated gene editing with nanoparticle delivery. Nature Communications 2016, 7: 13304. PMID: 27782131, PMCID: PMC5095181, DOI: 10.1038/ncomms13304.Peer-Reviewed Original ResearchConceptsNanoparticle deliveryGene correctionReversal of splenomegalyPeptide nucleic acidLow off-target effectsVivo correctionGenome editingOff-target effectsGene editingHaematopoietic stem cellsNucleic acidsDonor DNAStem cellsΓPNAΒ-thalassaemiaNanoparticlesDeliveryEditingSCF treatmentTriplex formation
2012
Reducing Mitochondrial ROS Improves Disease-related Pathology in a Mouse Model of Ataxia-telangiectasia
D'Souza AD, Parish IA, Krause DS, Kaech SM, Shadel GS. Reducing Mitochondrial ROS Improves Disease-related Pathology in a Mouse Model of Ataxia-telangiectasia. Molecular Therapy 2012, 21: 42-48. PMID: 23011031, PMCID: PMC3538311, DOI: 10.1038/mt.2012.203.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia TelangiectasiaAtaxia Telangiectasia Mutated ProteinsCatalaseCD8-Positive T-LymphocytesCell Cycle ProteinsDisease Models, AnimalDNA-Binding ProteinsHematopoiesisImmunologic MemoryLymphomaMiceMice, KnockoutMitochondriaProtein Serine-Threonine KinasesReactive Oxygen SpeciesThymus NeoplasmsTumor Suppressor ProteinsConceptsMitochondrial reactive oxygen speciesReactive oxygen speciesAtaxia telangiectasiaT cell developmental defectsDNA damage responseDisease ataxia telangiectasiaMitochondrial ROS productionOverexpression of catalaseATM kinaseRedox sensingDevelopmental defectsLatter phenotypePartial rescueBone marrow hematopoiesisCancer predispositionNull mouse modelMitochondrial dysfunctionMacrophage differentiationTORC1ROS productionCancer developmentOxygen speciesMouse modelTS pathologyMarrow hematopoiesis
2011
Increased Tubular Proliferation as an Adaptive Response to Glomerular Albuminuria
Guo JK, Marlier A, Shi H, Shan A, Ardito TA, Du ZP, Kashgarian M, Krause DS, Biemesderfer D, Cantley LG. Increased Tubular Proliferation as an Adaptive Response to Glomerular Albuminuria. Journal Of The American Society Of Nephrology 2011, 23: 429-437. PMID: 22193389, PMCID: PMC3294312, DOI: 10.1681/asn.2011040396.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminuriaAnimalsAxl Receptor Tyrosine KinaseCell ProliferationDisease Models, AnimalFemaleHeparin-binding EGF-like Growth FactorIntegrasesIntercellular Signaling Peptides and ProteinsIntracellular Signaling Peptides and ProteinsKidney GlomerulusKidney Tubules, ProximalMaleMembrane ProteinsMiceMice, TransgenicPodocytesProteinuriaProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesConceptsGlomerular proteinuriaTubular injuryTubular proliferationStructural glomerular injuryProteinuric renal diseaseOnset of albuminuriaRenal tubular atrophyDiphtheria toxin receptorRenal tubular cellsProximal tubule cellsGlomerular albuminuriaRenal failureSystemic inflammationTubular damageProgressive glomerulosclerosisRenal diseaseTubular atrophyGlomerular injuryRenal responsePodocyte lossProliferative responseTubular cellsAnimal modelsProteinuriaReceptor Axl
2008
Rectal Potential Difference and the Functional Expression of CFTR in the Gastrointestinal Epithelia in Cystic Fibrosis Mouse Models
Weiner SA, Caputo C, Bruscia E, Ferreira EC, Price JE, Krause DS, Egan ME. Rectal Potential Difference and the Functional Expression of CFTR in the Gastrointestinal Epithelia in Cystic Fibrosis Mouse Models. Pediatric Research 2008, 63: 73-78. PMID: 18043508, DOI: 10.1203/pdr.0b013e31815b4bc6.Peer-Reviewed Original ResearchConceptsRectal potential differenceMouse modelCF mouse modelsCystic fibrosisFibrosis mouse modelDifferent mouse modelsCystic fibrosis mouse modelUssing chamber methodEffects of interventionsAutosomal recessive diseasePharmacologic interventionsRespiratory epitheliumElectrophysiologic phenotypeGastrointestinal epitheliumCF transmembrane conductance regulator (CFTR) geneRecessive diseaseVivo methodsVivo assaysVivo dataCFTR functionTransmembrane conductance regulator geneReliable assayEpitheliumInterventionCFTR expression
2006
Threshold of Lung Injury Required for the Appearance of Marrow‐Derived Lung Epithelia
Herzog EL, Van Arnam J, Hu B, Krause DS. Threshold of Lung Injury Required for the Appearance of Marrow‐Derived Lung Epithelia. Stem Cells 2006, 24: 1986-1992. PMID: 16868209, DOI: 10.1634/stemcells.2005-0579.Peer-Reviewed Original ResearchConceptsBone marrow-derived cellsBone marrow transplantationLung injuryMarrow transplantationLung epitheliumEngraftment of BMDCsLocal host factorsSex-mismatched bone marrow transplantationMarrow-derived cellsType II pneumocytesMyeloablative radiationLung damageHematopoietic chimerismEpithelial chimerismApparent injuryInjuryTransplantationHost factorsEpitheliumEpithelial cellsEpithelial phenotypeLungChimerismPneumocytesPhenotypic changesPrevention of mesangial sclerosis by bone marrow transplantation
Guo J, Ardito TA, Kashgarian M, Krause DS. Prevention of mesangial sclerosis by bone marrow transplantation. Kidney International 2006, 70: 910-913. PMID: 16850025, DOI: 10.1038/sj.ki.5001698.Peer-Reviewed Original ResearchConceptsBone marrow transplantationMesangial sclerosisMarrow transplantationUrinary albumin lossSimilar therapeutic effectsOnset of diseaseWild-type BMIntrarenal administrationRenal functionRenal histologyRenal diseaseDisease onsetRenal pathologyBM cellsTherapeutic effectEngraftment levelsRenal cellsAlbumin lossKidney samplesMiceSclerosisTransplantationUntreated controlsDiseaseAdministration
2005
Integration of engrafted Schwann cells into injured peripheral nerve: Axonal association and nodal formation on regenerated axons
Radtke C, Akiyama Y, Lankford KL, Vogt PM, Krause DS, Kocsis JD. Integration of engrafted Schwann cells into injured peripheral nerve: Axonal association and nodal formation on regenerated axons. Neuroscience Letters 2005, 387: 85-89. PMID: 16084645, PMCID: PMC2605373, DOI: 10.1016/j.neulet.2005.06.073.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxotomyCell Adhesion Molecules, NeuronalCell CompartmentationCytoplasmDisease Models, AnimalFemaleGreen Fluorescent ProteinsImmunohistochemistryMaleMiceMice, Inbred C57BLMicroscopy, Electron, TransmissionMyelin SheathNAV1.6 Voltage-Gated Sodium ChannelNerve RegenerationNerve Tissue ProteinsPeripheral Nerve InjuriesPeripheral NervesRanvier's NodesSchwann CellsSciatic NeuropathySodium ChannelsY ChromosomeConceptsWild-type miceSchwann cellsMyelin-forming cellsRegenerated axonsSodium channelsType miceRegenerated peripheral nerve fibersFemale wild-type miceDonor cellsMale donor cellsPeripheral nerve fibersSciatic nerve axonsImmuno-electron microscopic analysisCrush injuryCrush sitePeripheral nervesDonor originMale miceNerve fibersNerve axonsNodal formationAxonsNerveMiceAxonal associations