Featured Publications
VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis.
Kim S, Adams T, Hu Q, Shin H, Chae G, Lee S, Sharma L, Kwon H, Lee F, Park H, Huh W, Manning E, Kaminski N, Sauler M, Chen L, Song J, Kim T, Kang M. VISTA (PD-1H) Is a Crucial Immune Regulator to Limit Pulmonary Fibrosis. American Journal Of Respiratory Cell And Molecular Biology 2023, 69: 22-33. PMID: 36450109, PMCID: PMC10324045, DOI: 10.1165/rcmb.2022-0219oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisImmune regulatorsTherapeutic potentialHuman idiopathic pulmonary fibrosisCrucial immune regulatorsNovel immune regulatorPulmonary fibrosis micePulmonary fibrosis modelNovel therapeutic targetRole of VISTAWild-type littermatesMonocyte-derived macrophagesT lymphocyte lineageVISTA expressionIPF treatmentAntibody treatmentImmune landscapeFibrotic mediatorsLung fibrosisFibrosis miceInflammatory responseFibrosis modelMyeloid populationsTherapeutic targetTreating ‘Septic’ With Enhanced Antibiotics and ‘Arthritis’ by Mitigation of Excessive Inflammation
Kwon HK, Dussik CM, Kim SH, Kyriakides TR, Oh I, Lee FY. Treating ‘Septic’ With Enhanced Antibiotics and ‘Arthritis’ by Mitigation of Excessive Inflammation. Frontiers In Cellular And Infection Microbiology 2022, 12: 897291. PMID: 35755835, PMCID: PMC9218192, DOI: 10.3389/fcimb.2022.897291.Peer-Reviewed Original ResearchConceptsSeptic arthritisBacterial burdenAntibiotic treatmentMurine modelTherapeutic goalsConcurrent antimicrobial therapyDistinct therapeutic goalsGeneration of inflammationMRSA septic arthritisSeptic knee arthritisInflammatory joint conditionsArticular cartilageMitigation of inflammationPost-antibiotic treatmentNovel therapeutic strategiesSeptic arthritis modelArticular cartilage damageEx vivo modelArticular cartilage integrityInflammatory arthritisInhibitors of ERKInflammatory profileMRSA infectionSynovial tissueExcessive inflammationEnhancement of Impaired MRSA‐Infected Fracture Healing by Combinatorial Antibiotics and Modulation of Sustained Inflammation
Yu KE, Kwon H, Dussik CM, Cahill SV, Back J, Alder KD, Lee FY. Enhancement of Impaired MRSA‐Infected Fracture Healing by Combinatorial Antibiotics and Modulation of Sustained Inflammation. Journal Of Bone And Mineral Research 2020, 37: 1352-1365. PMID: 35616626, DOI: 10.1002/jbmr.4570.Peer-Reviewed Original ResearchConceptsMethicillin-resistant Staphylococcus aureusExcessive inflammationAntibiotic treatmentFracture healingTrametinib therapyInfected fracturesPro-inflammatory cytokine levelsPostoperative antibiotic administrationSetting of infectionMale C57BL/6 miceSystemic antibiotic treatmentAdjunctive therapeutic agentMRSA-infected miceImpaired callus formationFemoral fracture modelTherapeutic cohortCytokine levelsMRSA infectionMusculoskeletal infectionsPostoperative intervalsSystemic vancomycinAntibiotic administrationCytokine analysisC57BL/6 miceIntramedullary nailingConstruction and evaluation of a clinically relevant model of septic arthritis
Kwon H, Yu K, Lee F. Construction and evaluation of a clinically relevant model of septic arthritis. Lab Animal 2022, 52: 11-26. PMID: 36564668, DOI: 10.1038/s41684-022-01089-7.Peer-Reviewed Original ResearchConceptsSeptic arthritisAnimal modelsMethicillin-resistant Staphylococcus aureus culturesIntra-articular inflammationReproducible animal modelRelevant mouse modelExperimental animal modelsMRSA infectionCartilage destructionC57BL/6J miceInflammatory pathologyJoint diseaseTherapeutic medicationsMouse modelArthritisSynovial fluidClinical relevancePotential treatmentHuman patientsKnee jointDirect inoculationAureus culturesMRSAMiceStaphylococcus aureus culturesDual therapeutic targeting of intra-articular inflammation and intracellular bacteria enhances chondroprotection in septic arthritis
Kwon HK, Lee I, Yu KE, Cahill SV, Alder KD, Lee S, Dussik CM, Back J, Choi J, Song L, Kyriakides TR, Lee FY. Dual therapeutic targeting of intra-articular inflammation and intracellular bacteria enhances chondroprotection in septic arthritis. Science Advances 2021, 7: eabf2665. PMID: 34172438, PMCID: PMC8232912, DOI: 10.1126/sciadv.abf2665.Peer-Reviewed Original ResearchConceptsIntra-articular inflammationSeptic arthritisBacterial infectionsDual therapeutic targetingKnee septic arthritisPromising new therapeutic strategyArticular cartilageChallenging clinical problemNovel treatment modalitiesIntracellular bacteriaNew therapeutic strategiesAdjuvant targetingTreatment modalitiesBacterial eradicationSuccessful treatmentHost inflammationCausative bacteriaMurine modelTherapeutic strategiesArthritisTherapeutic goalsClinical problemTherapeutic targetingInflammationVital organsBiocompatibility of platinum-based bulk metallic glass in orthopedic applications
Loye AM, Kwon HK, Dellal D, Ojeda R, Lee S, Davis R, Nagle N, Doukas PG, Schroers J, Lee FY, Kyriakides TR. Biocompatibility of platinum-based bulk metallic glass in orthopedic applications. Biomedical Materials 2021, 16: 045018. PMID: 33873168, DOI: 10.1088/1748-605x/abf981.Peer-Reviewed Original ResearchConceptsBulk metallic glassPt-BMGPlatinum-based bulk metallic glassMetallic glassesConventional metallic implantsCorrosion resistanceHigh strengthMechanical testingOrthopedic applicationsBone applicationsMetallic implantsMicro-computed tomographyAmorphous metalsTitaniumWearBiocompatibilitySimilar biocompatibilityFurther processingGlassDuctilityNanopatternsNanoscaleApplicationsMesenchymal stem cellsStrengthLocally delivered adjuvant biofilm‐penetrating antibiotics rescue impaired endochondral fracture healing caused by MRSA infection
Cahill SV, Kwon H, Back J, Lee I, Lee S, Alder KD, Hao Z, Yu KE, Dussik CM, Kyriakides T, Lee F. Locally delivered adjuvant biofilm‐penetrating antibiotics rescue impaired endochondral fracture healing caused by MRSA infection. Journal Of Orthopaedic Research® 2021, 39: 402-414. PMID: 33336805, DOI: 10.1002/jor.24965.Peer-Reviewed Original ResearchConceptsHigh-dose rifampinFracture healingMRSA infectionMethicillin-resistant Staphylococcus aureus osteomyelitisColony-forming unitsTissue bacterial loadStaphylococcus aureus osteomyelitisReactive bone formationRadiographic union scaleEndochondral fracture healingBacterial CFU countsPoor callus formationSoft callus formationTibia scoresRifampin therapyDevastating complicationMRSA colonizationClinical efficacyInfected fracturesTibial radiographsTreatment responseMurine modelIntramedullary pinOpen fracturesO stainSmoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains
Hao Z, Li J, Li B, Alder KD, Cahill SV, Munger AM, Lee I, Kwon H, Back J, Xu S, Kang M, Lee FY. Smoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains. Journal Of Bone And Mineral Research 2020, 36: 186-198. PMID: 32866293, PMCID: PMC9057220, DOI: 10.1002/jbmr.4175.Peer-Reviewed Original ResearchConceptsCigarette smoke exposureCigarette smokingFracture healingSmoke exposureMurine modelMolecular alterationsBALB/cJ miceBiomechanical testingPro-inflammatory mediatorsCytokine/chemokine analysisImpaired fracture healingMultiplex cytokine/chemokine analysisInitial inflammatory responseFracture healing capacityBALB/cJProgenitor cell activitySmoking miceTransverse femoral osteotomyFemoral osteotomyImmune cellsChemokine analysisInflammatory responseFracture hematomaHigh riskMurine strains
2024
Unique Spatial Transcriptomic Profiling of the Murine Femoral Fracture Callus: A Preliminary Report
Jiang W, Caruana D, Back J, Lee F. Unique Spatial Transcriptomic Profiling of the Murine Femoral Fracture Callus: A Preliminary Report. Cells 2024, 13: 522. PMID: 38534368, PMCID: PMC10969736, DOI: 10.3390/cells13060522.Peer-Reviewed Original ResearchConceptsMDA-MB-231Transcriptomic platformsGene expressionSpatially localized gene expressionMDA-MB-231 metastatic breast cancer cellsSpatial transcriptomics platformGenetic expression changesFracture healingMetastatic breast cancer cellsBreast cancer cellsImpaired fracture healingSingle-cell RNALocal gene expressionSpatial transcriptomic profilingFracture callus formationGenomic heterogeneitySequencing techniquesDisrupt bone homeostasisTranscriptome profilingIn situ hybridizationExpression changesSoft callusPathological fracturesWild-typeSpatial transcriptomics
2023
Parathyroid hormone therapy improves MRSA-infected fracture healing in a murine diabetic model
Kwon H, Cahill S, Yu K, Alder K, Dussik C, Jeong J, Back J, Lee F. Parathyroid hormone therapy improves MRSA-infected fracture healing in a murine diabetic model. Frontiers In Cellular And Infection Microbiology 2023, 13: 1230568. PMID: 37829606, PMCID: PMC10565816, DOI: 10.3389/fcimb.2023.1230568.Peer-Reviewed Original ResearchConceptsFracture healingTeriparatide treatmentType 2 diabetic mouse modelType 2 diabetes mellitus miceBone volume/total volumeMurine diabetic modelTotal mineral densityIntermittent parathyroid hormoneSystemic antibiotic therapyImpairs fracture healingPoor fracture healingAdjuvant therapeutic agentDiabetes mellitus miceDiabetic mouse modelBlood glucose levelsCombination of antibioticsRadiographic union scaleTibia fracture modelIPTH treatmentSeptic nonunionNondiabetic counterpartsT2DM miceHormone therapyAntibiotic therapyMRSA infection
2019
A cell-penetrating peptide blocks Toll-like receptor-mediated downstream signaling and ameliorates autoimmune and inflammatory diseases in mice
Kwon HK, Patra MC, Shin HJ, Gui X, Achek A, Panneerselvam S, Kim DJ, Song SJ, Hong R, Kim KS, Kim YG, Lee FY, Hahm DH, Lee SH, Choi S. A cell-penetrating peptide blocks Toll-like receptor-mediated downstream signaling and ameliorates autoimmune and inflammatory diseases in mice. Experimental & Molecular Medicine 2019, 51: 1-19. PMID: 31028244, PMCID: PMC6486608, DOI: 10.1038/s12276-019-0244-0.Peer-Reviewed Original ResearchConceptsToll-like receptorsCollagen-induced arthritisInflammatory diseasesRodent modelsOverexpression of TLRsMultiple Toll-like receptorsAutoimmune/inflammatory diseasesSecretion of lipopolysaccharideDamage-associated molecular patternsInflammatory signaling cascadesIL-1β secretionNumerous inflammatory diseasesRheumatoid arthritisProinflammatory cytokinesLiver damageTLR4 TIR domainImmune responseAnimal studiesTherapeutic potentialToll/interleukinMolecular patternsMRNA levelsDiseaseArthritisSelective inhibitor
2017
Dried plum alleviates symptoms of inflammatory arthritis in TNF transgenic mice
Mirza F, Lorenzo J, Drissi H, Lee FY, Soung DY. Dried plum alleviates symptoms of inflammatory arthritis in TNF transgenic mice. The Journal Of Nutritional Biochemistry 2017, 52: 54-61. PMID: 29149648, DOI: 10.1016/j.jnutbio.2017.10.002.Peer-Reviewed Original ResearchConceptsTumor necrosis factorTransgenic miceRheumatoid arthritisNuclear factor-kappa B activationDP dietBone-preserving propertiesReduction of synovitisPresence of TNFFour-week treatmentOnset of arthritisResistant acid phosphatase-positive cellsAcid phosphatase-positive cellsDestruction of jointsHuman synovial fibroblastsTNF-transgenic miceHuman tumor necrosis factorKappa B activationActivated T cellsFormation of osteoclastsMouse bone marrow macrophagesBone marrow macrophagesArticular cartilagePostmenopausal womenInflammatory arthritisBone erosionTendon stem/progenitor cells regulate inflammation in tendon healing via JNK and STAT3 signaling
Tarafder S, Chen E, Jun Y, Kao K, Sim KH, Back J, Lee FY, Lee CH. Tendon stem/progenitor cells regulate inflammation in tendon healing via JNK and STAT3 signaling. The FASEB Journal 2017, 31: 3991-3998. PMID: 28533328, PMCID: PMC5572690, DOI: 10.1096/fj.201700071r.Peer-Reviewed Original ResearchConceptsConnective tissue growth factorTendon stem/progenitor cellsIL-10 expressionStem/progenitor cellsIL-10TIMP-3 expressionTendon healingIL-1βProgenitor cellsTendon cellsElevated IL-10 expressionAnti-inflammatory IL-10Number of iNOSRat patellar tendonAnti-inflammatory roleAcute tendon injuryIL-6 expressionRegulation of inflammationTissue growth factorMMP-3 expressionNumber of CD146Improved tendon healingDifferent anatomic locationsWestern blot analysisPromising regenerative potentialCalreticulin inhibits inflammation‐induced osteoclastogenesis and bone resorption
Fischer CR, Mikami M, Minematsu H, Nizami S, Lee H, Stamer D, Patel N, Soung D, Back JH, Song L, Drissi H, Lee FY. Calreticulin inhibits inflammation‐induced osteoclastogenesis and bone resorption. Journal Of Orthopaedic Research® 2017, 35: 2658-2666. PMID: 28460421, PMCID: PMC8996436, DOI: 10.1002/jor.23587.Peer-Reviewed Original ResearchConceptsRecombinant human calreticulinIntracellular proteinsCalcium-binding chaperoneDifferent cell typesRecombinant formTranscription factorsFusion of monocytesExtracellular functionsNew therapeutic opportunitiesK activityCathepsin K activityCell typesCalreticulinCytoplasmic 1Anti-osteoclastogenic effectPrecursor cellsMetastatic bone cancerFactor 1Human calreticulinActivated T cellsOsteoclast precursor cellsProteinNuclear factorC-fosMouse calvarial bones
2016
Tissue engineering advances in spine surgery
Makhni MC, Caldwell JM, Saifi C, Fischer CR, Lehman RA, Lenke LG, Lee FY. Tissue engineering advances in spine surgery. Regenerative Medicine 2016, 11: 211-222. PMID: 26877156, DOI: 10.2217/rme.16.3.Peer-Reviewed Original ResearchConceptsTissue-engineered bone graftsBiomimetic 3D scaffoldsTissue-engineered constructsBone graftTissue engineering advancesDonor site painNanoscale technologiesSite painEngineering advancesHematoma formationVascular injurySpine surgeryBone graftingBone allograftSurgery applicationsMesenchymal stem cellsTissue graftViable boneIntervertebral disc regeneration strategiesHuman tissue graftsGraftGold standardOsteoinductive capabilityDisease transmissionOwn disadvantages
2015
Activation of Protein Kinase A in Mature Osteoblasts Promotes a Major Bone Anabolic Response
Tascau L, Gardner T, Anan H, Yongpravat C, Cardozo CP, Bauman WA, Lee FY, Oh DS, Tawfeek HA. Activation of Protein Kinase A in Mature Osteoblasts Promotes a Major Bone Anabolic Response. Endocrinology 2015, 157: 112-126. PMID: 26488807, DOI: 10.1210/en.2015-1614.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsBone DensityCells, CulturedEnergy MetabolismEnzyme ActivationFemaleFemurLumbar VertebraeMaleMice, Inbred C57BLMice, TransgenicOsteoblastsOsteocytesOsteogenesisPoint MutationPromoter Regions, GeneticSex CharacteristicsUp-RegulationX-Ray MicrotomographyConceptsBone anabolic responseOb miceMature osteoblastsPKA activationHigher basal PKA activityControl miceAnabolic responseProtein kinase ASerum bone turnover markersBone volume/total volumeBone turnover markersBasal PKA activityFemur cortical thicknessTotal tissue areaActive PKAKinase AConstitutive activationPKA activityTurnover markersBone lossAnabolic drugsStructure model indexOsteoclast numberFemale miceBone massCA‐074Me compound inhibits osteoclastogenesis via suppression of the NFATc1 and c‐FOS signaling pathways
Patel N, Nizami S, Song L, Mikami M, Hsu A, Hickernell T, Chandhanayingyong C, Rho S, Compton JT, Caldwell J, Kaiser PB, Bai H, Lee HG, Fischer CR, Lee FY. CA‐074Me compound inhibits osteoclastogenesis via suppression of the NFATc1 and c‐FOS signaling pathways. Journal Of Orthopaedic Research® 2015, 33: 1474-1486. PMID: 25428830, DOI: 10.1002/jor.22795.Peer-Reviewed Original ResearchConceptsOsteolytic disordersOsteoclast biologyBone resorptionCA-074MeC-FOSMechanisms of cathepsinsCathepsin B knockout miceB knockout miceCathepsin B inhibitor CA-074Dose-dependent mannerOsteoclast resorption pitsCathepsin B inhibitionInhibits osteoclastogenesisNFATc1 pathwayNew therapiesOsteoclastogenic effectsCA-074Knockout miceLysosomal proteasesMature osteoclastsResorption pitsCathepsin KNew targetsOsteoclastsCompound inhibitsHarnessing endogenous stem/progenitor cells for tendon regeneration
Lee CH, Lee FY, Tarafder S, Kao K, Jun Y, Yang G, Mao JJ. Harnessing endogenous stem/progenitor cells for tendon regeneration. Journal Of Clinical Investigation 2015, 125: 2690-2701. PMID: 26053662, PMCID: PMC4563693, DOI: 10.1172/jci81589.Peer-Reviewed Original ResearchMeSH KeywordsAdult Stem CellsAnimalsCD146 AntigenCell DifferentiationCell ProliferationColony-Forming Units AssayConnective Tissue Growth FactorFocal Adhesion Kinase 1MAP Kinase Signaling SystemMultipotent Stem CellsRatsRats, Sprague-DawleyRegenerationTendon InjuriesTendonsTissue EngineeringWound HealingConceptsStem/progenitor cellsEndogenous stem/progenitor cellsProgenitor cellsCell transplantationTendon regenerationStem cell markers CD146Stem cell-based strategiesFAK/ERK1/2Cell-based strategiesRat modelTendon healingFunctional restorationNormal levelsMultilineage differentiation abilityClonogenic capacityCD146Tendon cellsSiRNA knockdownTransplantationVivo manipulationGremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential
Worthley DL, Churchill M, Compton JT, Tailor Y, Rao M, Si Y, Levin D, Schwartz MG, Uygur A, Hayakawa Y, Gross S, Renz BW, Setlik W, Martinez AN, Chen X, Nizami S, Lee HG, Kang HP, Caldwell JM, Asfaha S, Westphalen CB, Graham T, Jin G, Nagar K, Wang H, Kheirbek MA, Kolhe A, Carpenter J, Glaire M, Nair A, Renders S, Manieri N, Muthupalani S, Fox JG, Reichert M, Giraud AS, Schwabe RF, Pradere JP, Walton K, Prakash A, Gumucio D, Rustgi AK, Stappenbeck TS, Friedman RA, Gershon MD, Sims P, Grikscheit T, Lee FY, Karsenty G, Mukherjee S, Wang TC. Gremlin 1 Identifies a Skeletal Stem Cell with Bone, Cartilage, and Reticular Stromal Potential. Cell 2015, 160: 269-284. PMID: 25594183, PMCID: PMC4436082, DOI: 10.1016/j.cell.2014.11.042.Peer-Reviewed Original ResearchConceptsBone morphogenetic proteinStem cellsMarrow stromal cellsMesenchymal stem cellsGremlin-1Skeletal stem cellsTissue stem cellsFate-mapping experimentsStromal cellsMorphogenetic proteinsPostnatal skeletonBone developmentCell of originMesenchymal sheathCellsAdipocytesOsteoblastsExpressionBone marrowChondrocytesProteinBone remodelingPerisinusoidal spaceRemodelingFracture repair
2014
Effects of biomechanical forces on signaling in the cortical collecting duct (CCD)
Carrisoza-Gaytan R, Liu Y, Flores D, Else C, Lee HG, Rhodes G, Sandoval RM, Kleyman TR, Lee FY, Molitoris B, Satlin LM, Rohatgi R. Effects of biomechanical forces on signaling in the cortical collecting duct (CCD). American Journal Of Physiology. Renal Physiology 2014, 307: f195-f204. PMID: 24872319, PMCID: PMC4152160, DOI: 10.1152/ajprenal.00634.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutocrine CommunicationCell LineDinoprostoneEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFurosemideInjectionsIon TransportKidney CortexKidney Tubules, CollectingMechanotransduction, CellularMiceMicroscopy, Fluorescence, MultiphotonP38 Mitogen-Activated Protein KinasesParacrine CommunicationPhosphorylationPotassiumRatsRats, Sprague-DawleySodium ChlorideStress, MechanicalTime FactorsConceptsTubular fluid flow rateP-p38Biomechanical forcesCircumferential stretchIntravital microscopic approachP-ERK expressionFurosemide injectionPGE2 releaseIntracellular MAPKK secretionCollagen type IVCell culture modelTubular diameterEx vivoPGE2Fluid shear stressUnstretched controlsCCD cellsType IVP38 activationCulture modelMAPK signalingVivoPhysiological forcesCation transport