2023
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 target
2021
T3 Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies sphingosine kinase 1 as a potential therapeutic target
Reichmann M, Tezera L, Vallejo A, Vukmirovic M, Xiao R, Jogai S, Wilson S, Marshall, Jones, Leslie A, D’Armiento J, Kaminski N, Polak M, Elkington P. T3 Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies sphingosine kinase 1 as a potential therapeutic target. Thorax 2021, 76: a2-a3. DOI: 10.1136/thorax-2021-btsabstracts.3.Peer-Reviewed Original ResearchPotential therapeutic targetTherapeutic targetTB granulomasHost-directed therapeutic targetHuman tuberculosis granulomasImmunopathology of tuberculosisPathological host responsesInflammatory immune responseSphingosine kinase 1 inhibitionInflammatory mediator secretionImmune-related phenomenaDisease-specific mechanismsNew therapeutic approachesHuman TB granulomasDose-dependent mannerKinase 1 inhibitionDunnett's multiple comparison testMultiple comparison testHuman cell culture modelsTB patientsLymph nodesSarcoidosis patientsTB outcomesClinical featuresTuberculosis granulomasMechanisms of Hypoxia-Induced Pulmonary Arterial Stiffening in Mice Revealed by a Functional Genetics Assay of Structural, Functional, and Transcriptomic Data
Manning EP, Ramachandra AB, Schupp JC, Cavinato C, Raredon MSB, Bärnthaler T, Cosme C, Singh I, Tellides G, Kaminski N, Humphrey JD. Mechanisms of Hypoxia-Induced Pulmonary Arterial Stiffening in Mice Revealed by a Functional Genetics Assay of Structural, Functional, and Transcriptomic Data. Frontiers In Physiology 2021, 12: 726253. PMID: 34594238, PMCID: PMC8478173, DOI: 10.3389/fphys.2021.726253.Peer-Reviewed Original ResearchPulmonary arteryAdult male C57BL/6J miceElevated pulmonary arterial pressureChronic cardiopulmonary conditionsPulmonary arterial pressureMale C57BL/6J miceElastic pulmonary arteriesArterial pulse wave velocityPulse wave velocityPotential therapeutic targetPulmonary arterial stiffeningSmooth muscle cell phenotypeMuscle cell phenotypeSpecific transcriptomic changesArterial pressureArterial stiffeningHypoxic miceCardiopulmonary conditionsPulmonary circulationC57BL/6J miceSustained hypoxiaTherapeutic targetClinical importanceEndothelial proliferationArteryIntegrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets
Reichmann MT, Tezera LB, Vallejo AF, Vukmirovic M, Xiao R, Reynolds J, Jogai S, Wilson S, Marshall B, Jones MG, Leslie A, D'Armiento JM, Kaminski N, Polak ME, Elkington P. Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets. Journal Of Clinical Investigation 2021, 131 PMID: 34128839, PMCID: PMC8321576, DOI: 10.1172/jci148136.Peer-Reviewed Original ResearchConceptsTherapeutic targetTB granulomasHuman TB diseaseHuman tuberculosis granulomasNoninfectious granulomatous diseasesPathological host responsesSarcoidosis lymph nodesInflammatory immune responseSphingosine kinase 1 inhibitionInflammatory mediator secretionPotential therapeutic targetHuman TB granulomasKinase 1 inhibitionHuman cell culture modelsInfected granulomasTB diseaseLymph nodesTB outcomesTuberculosis granulomasStandard treatmentSphingosine kinase 1Granulomatous diseaseLaser capture microdissectionMediator secretionExtensive infection
2020
An allosteric site on MKP5 reveals a strategy for small-molecule inhibition
Gannam Z, Min K, Shillingford SR, Zhang L, Herrington J, Abriola L, Gareiss PC, Pantouris G, Tzouvelekis A, Kaminski N, Zhang X, Yu J, Jamali H, Ellman JA, Lolis E, Anderson KS, Bennett AM. An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling 2020, 13 PMID: 32843541, PMCID: PMC7569488, DOI: 10.1126/scisignal.aba3043.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAmino Acid SequenceAnimalsCell DifferentiationCell LineDual-Specificity PhosphatasesEnzyme InhibitorsFemaleHigh-Throughput Screening AssaysHumansKineticsMiceMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesMyoblastsProtein BindingSequence Homology, Amino AcidSignal TransductionSmall Molecule LibrariesConceptsDystrophic muscle diseaseMitogen-activated protein kinaseMuscle diseaseTGF-β1Promising therapeutic targetP38 mitogen-activated protein kinaseTherapeutic strategiesTherapeutic targetSmall molecule inhibitionSmad2 phosphorylationDiseasePotential targetSmall-molecule screenInhibitorsTreatmentInhibition
2019
Role of dual-specificity protein phosphatase DUSP10/MKP-5 in pulmonary fibrosis
Xylourgidis N, Min K, Ahangari F, Yu G, Herazo-Maya JD, Karampitsakos T, Aidinis V, Binzenhöfer L, Bouros D, Bennett AM, Kaminski N, Tzouvelekis A. Role of dual-specificity protein phosphatase DUSP10/MKP-5 in pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2019, 317: l678-l689. PMID: 31483681, PMCID: PMC6879900, DOI: 10.1152/ajplung.00264.2018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticBleomycinDual-Specificity PhosphatasesFemaleFibroblastsHumansMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesPhosphorylationPulmonary FibrosisSignal TransductionTransforming Growth Factor beta1ConceptsPulmonary fibrosisLung fibrosisFibrogenic genesLung fibroblastsM1 macrophage phenotypeIdiopathic pulmonary fibrosisHuman lung fibrosisGrowth factor-β1Levels of hydroxyprolineProtein kinase phosphatase 5IPF lungsReduced fibrosisMuscle fibrosisProfibrogenic effectsTGF-β1Smad7 levelsTherapeutic targetAnimal modelsFactor-β1FibrosisSmad3 phosphorylationEnhanced p38 MAPK activityP38 MAPK activityMyofibroblast differentiationMKP-5 expression
2017
Integrin alpha 11 in the regulation of the myofibroblast phenotype: implications for fibrotic diseases
Bansal R, Nakagawa S, Yazdani S, van Baarlen J, Venkatesh A, Koh AP, Song WM, Goossens N, Watanabe H, Beasley MB, Powell CA, Storm G, Kaminski N, van Goor H, Friedman SL, Hoshida Y, Prakash J. Integrin alpha 11 in the regulation of the myofibroblast phenotype: implications for fibrotic diseases. Experimental & Molecular Medicine 2017, 49: e396-e396. PMID: 29147013, PMCID: PMC5704196, DOI: 10.1038/emm.2017.213.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationDisease Models, AnimalFibrosisGene Expression RegulationGene Knockdown TechniquesHedgehog ProteinsHepatic Stellate CellsHumansImmunohistochemistryIntegrin alpha ChainsKidney DiseasesLiver CirrhosisMiceMyofibroblastsPhenotypeSignal TransductionTransforming Growth Factor betaConceptsHepatic stellate cellsFibrotic parametersMouse modelStellate cellsTissue fibrosisIntegrin alpha 11Alpha 11Smooth muscle actin-positive myofibroblastsLiver fibrosis mouse modelHuman hepatic stellate cellsMyofibroblast phenotypeFibrosis mouse modelPromising therapeutic targetActin-positive myofibroblastsCause of mortalityGrowth factor βAberrant extracellular matrixImpaired contractilityFibrogenic signalingFibrotic organsFibrogenic processExtracellular matrixTherapeutic targetOrgan fibrosisMyofibroblastic differentiation
2016
SH2 Domain–Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis
Tzouvelekis A, Yu G, Lino Cardenas CL, Herazo-Maya JD, Wang R, Woolard T, Zhang Y, Sakamoto K, Lee H, Yi JS, DeIuliis G, Xylourgidis N, Ahangari F, Lee PJ, Aidinis V, Herzog EL, Homer R, Bennett AM, Kaminski N. SH2 Domain–Containing Phosphatase-2 Is a Novel Antifibrotic Regulator in Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2016, 195: 500-514. PMID: 27736153, PMCID: PMC5378419, DOI: 10.1164/rccm.201602-0329oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisProfibrotic stimuliLung fibroblastsChronic fatal lung diseaseMyofibroblast differentiationPrimary human lung fibroblastsFatal lung diseaseNovel therapeutic strategiesVivo therapeutic effectPotential therapeutic usefulnessHuman lung fibroblastsMouse lung fibroblastsDismal prognosisFibroblastic fociLung fibrosisLung diseaseBleomycin modelTherapeutic effectTherapeutic usefulnessTherapeutic strategiesTherapeutic targetTransgenic miceFibrosisSHP2 overexpression
2012
The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets
Pode‐Shakked N, Shukrun R, Mark‐Danieli M, Tsvetkov P, Bahar S, Pri‐Chen S, Goldstein RS, Rom‐Gross E, Mor Y, Fridman E, Meir K, Simon A, Magister M, Kaminski N, Goldmacher VS, Harari‐Steinberg O, Dekel B. The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets. EMBO Molecular Medicine 2012, 5: 18-37. PMID: 23239665, PMCID: PMC3569651, DOI: 10.1002/emmm.201201516.Peer-Reviewed Original ResearchMeSH KeywordsAC133 AntigenAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAnimalsAntibodies, MonoclonalAntigens, CDCD56 AntigenCell DifferentiationCell ProliferationCell SeparationGene ExpressionGlycoproteinsHumansKidney NeoplasmsMaytansineMiceMice, Inbred NODMice, SCIDNeoplastic Stem CellsPeptidesRetinal DehydrogenaseTumor Cells, CulturedTumor Stem Cell AssayWilms TumorXenograft Model Antitumor AssaysConceptsNew therapeutic targetsTherapeutic targetPediatric solid tumorsPoor patient prognosisCancer initiating cellsMultiple xenograft modelsHuman WilmsCancer stem cellsAldehyde dehydrogenase activityMiR-200 familyPrimary tumorPatient prognosisRenal malignancyImmunodeficient micePediatric cancerXenograft modelTumor xenograftsXenograft cellsSolid tumorsTumor biologyComplete eradicationPediatric renal malignancyInitiating cellsProtein expressionTumors
2011
MicroRNAs in idiopathic pulmonary fibrosis
Pandit KV, Milosevic J, Kaminski N. MicroRNAs in idiopathic pulmonary fibrosis. Translational Research 2011, 157: 191-199. PMID: 21420029, DOI: 10.1016/j.trsl.2011.01.012.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisIPF lungsPulmonary fibrosisLung fibrosisMiR-155Vascular endothelial growth factor (VEGF) pathwayEndothelial growth factor pathwayLethal fibrotic lung diseaseFibrotic lung diseaseMiR-29Upregulated miR-155Growth factor-β1Epithelial-mesenchymal transitionGrowth factor pathwaysLung epithelial cellsLung diseaseProfibrotic effectsBleomycin modelRole of microRNAsTherapeutic targetFactor-β1FibrosisMesenchymal transitionFactor pathwayLet-7 family members
2008
A Role for the Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis
Englert JM, Hanford LE, Kaminski N, Tobolewski JM, Tan RJ, Fattman CL, Ramsgaard L, Richards TJ, Loutaev I, Nawroth PP, Kasper M, Bierhaus A, Oury TD. A Role for the Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis. American Journal Of Pathology 2008, 172: 583-591. PMID: 18245812, PMCID: PMC2258251, DOI: 10.2353/ajpath.2008.070569.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAdvanced glycation end productsRAGE-null micePulmonary fibrosisGlycation end productsIPF pathogenesisMouse modelNovel therapeutic targetHealthy adult animalsIPF patientsWild-type controlsDismal prognosisSevere fibrosisIPF tissueEffective therapyFibrotic lungsTherapeutic targetHistological scoringFibrosisLoss of RAGECell surface receptorsAdult animalsMiceEnd productsSoluble isoform
2006
Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis
Wang XM, Zhang Y, Kim HP, Zhou Z, Feghali-Bostwick CA, Liu F, Ifedigbo E, Xu X, Oury TD, Kaminski N, Choi AM. Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. Journal Of Experimental Medicine 2006, 203: 2895-2906. PMID: 17178917, PMCID: PMC1850940, DOI: 10.1084/jem.20061536.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsBleomycinCaveolin 1Collagen Type IEpithelial CellsExtracellular MatrixFibroblastsFibronectinsFibrosisGene ExpressionHumansHydroxyprolineJNK Mitogen-Activated Protein KinasesLungMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase 8PhosphorylationPulmonary FibrosisRNA, Small InterferingSmad2 ProteinTransfectionTransforming Growth Factor beta1ConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisCav-1 expressionCav-1Pulmonary fibroblastsPrimary pulmonary fibroblastsNovel therapeutic targetProgressive chronic disorderLung tissue samplesActivation of fibroblastsGrowth factor beta1Smad signaling cascadesHuman pulmonary fibroblastsC-Jun N-terminal kinase (JNK) pathwayIPF patientsLung fibrosisProfibrotic cytokinesChronic disordersN-terminal kinase pathwayLung tissueTherapeutic targetFibrosisHydroxyproline contentHistological analysisMarked reduction
2002
Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans
Zuo F, Kaminski N, Eugui E, Allard J, Yakhini Z, Ben-Dor A, Lollini L, Morris D, Kim Y, DeLustro B, Sheppard D, Pardo A, Selman M, Heller RA. Gene expression analysis reveals matrilysin as a key regulator of pulmonary fibrosis in mice and humans. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 6292-6297. PMID: 11983918, PMCID: PMC122942, DOI: 10.1073/pnas.092134099.Peer-Reviewed Original ResearchConceptsPulmonary fibrosisFibrotic lungsHuman pulmonary fibrosisPotential therapeutic targetGene expression analysisClinical diseaseSmooth muscleKnockout miceTherapeutic targetFibrosisHuman tissue samplesUntreatable groupLungTissue samplesMolecular pathwaysGlobal gene expression analysisExtracellular matrix formationMiceExpression analysisMatrilysinMolecular mechanismsKey regulatorGene expression patternsExpression patternsOligonucleotide microarrays