Featured Publications
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
2022
Human neutrophil development and functionality are enabled in a humanized mouse model
Zheng Y, Sefik E, Astle J, Karatepe K, Öz HH, Solis AG, Jackson R, Luo HR, Bruscia EM, Halene S, Shan L, Flavell RA. Human neutrophil development and functionality are enabled in a humanized mouse model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2121077119. PMID: 36269862, PMCID: PMC9618085, DOI: 10.1073/pnas.2121077119.Peer-Reviewed Original ResearchConceptsHumanized mouse modelMouse modelHuman immune systemHuman neutrophilsImmune systemFunctional human immune systemGranulocyte colony-stimulating factorUnique mouse modelColony-stimulating factorHuman G-CSFMISTRG miceG-CSF receptor geneBacterial burdenInfectious challengeG-CSFNeutrophilsMiceNeutrophil developmentReceptor geneDisease
2020
Humanized mice as preclinical models for myeloid malignancies
Gbyli R, Song Y, Halene S. Humanized mice as preclinical models for myeloid malignancies. Biochemical Pharmacology 2020, 174: 113794. PMID: 31926939, DOI: 10.1016/j.bcp.2020.113794.Books
2019
Functional Analysis of Human Hematopoietic Stem Cells In Vivo in Humanized Mice
Song Y, Gbyli R, Fu X, Halene S. Functional Analysis of Human Hematopoietic Stem Cells In Vivo in Humanized Mice. Methods In Molecular Biology 2019, 2097: 273-289. PMID: 31776933, DOI: 10.1007/978-1-0716-0203-4_18.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHematopoietic stem cellsHematopoietic stem cell functionFunctional hematopoietic stem cellsStem cell functionStem cellsCell-intrinsic functionHuman hematopoietic stem cellsOrganismal contextFunctional analysisCell functionIntrinsic functionCell sourceCellular productsChimeric miceStem cell therapyCellsReprogrammingMouse modelMajor advancesCell therapyMiceVivoFunction
2016
Peripheral blood CD34+ cells efficiently engraft human cytokine knock-in mice
Saito Y, Ellegast JM, Rafiei A, Song Y, Kull D, Heikenwalder M, Rongvaux A, Halene S, Flavell RA, Manz MG. Peripheral blood CD34+ cells efficiently engraft human cytokine knock-in mice. Blood 2016, 128: 1829-1833. PMID: 27543436, PMCID: PMC5054696, DOI: 10.1182/blood-2015-10-676452.Peer-Reviewed Original ResearchConceptsPeripheral blood CD34Higher engraftment levelsColony-stimulating factorBone marrowEngraftment levelsHuman hemato-lymphoid systemBlood CD34Granulocyte-macrophage colony-stimulating factorAdult recipient miceNonobese diabetic/Macrophage colony-stimulating factorSignal regulatory protein αCord blood-derived CD34Blood-derived CD34Regulatory protein αMISTRG miceAdult recipientsRecipient miceDiabetic/T cellsNonhematopoietic organsMyeloid cellsImmune systemCD34Mice
2014
Development and function of human innate immune cells in a humanized mouse model
Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV, Teichmann LL, Saito Y, Marches F, Halene S, Palucka AK, Manz MG, Flavell RA. Development and function of human innate immune cells in a humanized mouse model. Nature Biotechnology 2014, 32: 364-372. PMID: 24633240, PMCID: PMC4017589, DOI: 10.1038/nbt.2858.Peer-Reviewed Original ResearchSRF is required for neutrophil migration in response to inflammation
Taylor A, Tang W, Bruscia EM, Zhang PX, Lin A, Gaines P, Wu D, Halene S. SRF is required for neutrophil migration in response to inflammation. Blood 2014, 123: 3027-3036. PMID: 24574460, PMCID: PMC4014845, DOI: 10.1182/blood-2013-06-507582.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsAnimalsBlotting, WesternCell AdhesionCell MovementChemokinesGene ExpressionInflammationIntegrinsMiceMice, KnockoutMice, TransgenicMicroscopy, ConfocalNeutrophilsN-Formylmethionine Leucyl-PhenylalaninePolymerizationReverse Transcriptase Polymerase Chain ReactionSerum Response FactorSignal TransductionConceptsKO neutrophilsNeutrophil functionNormal neutrophil numbersSerum response factorSites of inflammationRole of SRFLoss of SRFNeutrophil numbersNeutrophil migrationMalignant processNeutrophilsCytokine stimuliChemokine gradientsCell functionExpression levelsIntegrin expression levelsInflammationMicePrimary defenseMegakaryocyte maturationNormal cell functionVivoCellular adhesionMaster regulatorIntegrin activation
2012
MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation
Smith EC, Thon JN, Devine MT, Lin S, Schulz VP, Guo Y, Massaro SA, Halene S, Gallagher P, Italiano JE, Krause DS. MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation. Blood 2012, 120: 2317-2329. PMID: 22806889, PMCID: PMC3447785, DOI: 10.1182/blood-2012-04-420828.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DiphosphateAnimalsBleeding TimeBlood PlateletsBone Marrow CellsCells, CulturedCrosses, GeneticCytoplasmCytoskeletonGene Expression ProfilingHematopoiesisMegakaryocytesMiceMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisPlatelet ActivationThrombocytopeniaTrans-ActivatorsTranscription FactorsConceptsMegakaryocyte maturationPlatelet formationSerum response factorSerum response factor expressionMembrane organizationGene expressionMKL1MKL2Response factorDKO miceKO backgroundMegakaryocyte compartmentMegakaryocytesCritical roleMegakaryocyte ploidyExpressionMaturationKnockout miceFactor expressionCrucial roleHomologuesGenesMiceProlonged bleeding timeRole