Featured Publications
Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells
Tyagi T, Jain K, Yarovinsky TO, Chiorazzi M, Du J, Castro C, Griffin J, Korde A, Martin KA, Takyar SS, Flavell RA, Patel AA, Hwa J. Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells. Journal Of Experimental Medicine 2022, 220: e20212218. PMID: 36305874, PMCID: PMC9814191, DOI: 10.1084/jem.20212218.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PlateletsCarcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesLung NeoplasmsMiceReceptors, ImmunologicConceptsCD8 T cellsT cellsTLT-1Non-small cell lung cancer patientsCell lung cancer patientsTREM-like transcript-1Tumor immunosuppressive mechanismsT cell suppressionLung cancer patientsPatient T cellsNF-κB pathwayPatient-derived tumorsDistinct activation phenotypesNSCLC patientsImmunosuppressive mechanismsSyngeneic tumorsHumanized miceImmunoregulatory rolePrognostic significanceImmunocompetent miceCancer patientsCell suppressionActivation phenotypeReduced tumorTumor growthSOD2 in platelets: with age comes responsibility
Jain K, Gu S, Hwa J. SOD2 in platelets: with age comes responsibility. Journal Of Thrombosis And Haemostasis 2023, 21: 1077-1081. PMID: 36716965, DOI: 10.1016/j.jtha.2023.01.016.Peer-Reviewed Original ResearchPlatelet Mitochondrial Fusion and Function in Vascular Integrity
Tyagi T, Yarovinsky T, Faustino E, Hwa J. Platelet Mitochondrial Fusion and Function in Vascular Integrity. Circulation Research 2024, 134: 162-164. PMID: 38236952, PMCID: PMC10798220, DOI: 10.1161/circresaha.123.323867.Peer-Reviewed Original Research
2020
Reduced Platelet miR-223 Induction in Kawasaki Disease Leads to Severe Coronary Artery Pathology Through a miR-223/PDGFRβ Vascular Smooth Muscle Cell Axis
Zhang Y, Wang Y, Zhang L, Xia L, Zheng M, Zeng Z, Liu Y, Yarovinsky T, Ostriker AC, Fan X, Weng K, Su M, Huang P, Martin KA, Hwa J, Tang WH. Reduced Platelet miR-223 Induction in Kawasaki Disease Leads to Severe Coronary Artery Pathology Through a miR-223/PDGFRβ Vascular Smooth Muscle Cell Axis. Circulation Research 2020, 127: 855-873. PMID: 32597702, PMCID: PMC7486265, DOI: 10.1161/circresaha.120.316951.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAnimalsBlood PlateletsCase-Control StudiesCells, CulturedChildChild, PreschoolCoronary Artery DiseaseCoronary VesselsDisease Models, AnimalFemaleHumansInfantMaleMice, Inbred C57BLMice, KnockoutMicroRNAsMucocutaneous Lymph Node SyndromeMuscle, Smooth, VascularMyocytes, Smooth MusclePlatelet ActivationProspective StudiesReceptor, Platelet-Derived Growth Factor betaSeverity of Illness IndexSignal TransductionYoung AdultConceptsSevere coronary pathologyCoronary artery pathologyKawasaki diseaseCoronary pathologyArtery pathologyMiR-223Medial damageHealthy controlsVSMC dedifferentiationHallmark of KDMiR-223 knockout miceVascular smooth muscle cell dedifferentiationSmooth muscle cell dedifferentiationPlatelet miR-223Platelet-derived miRNAsVSMC differentiationMedial elastic fibersMiR-223 levelsMuscle cell dedifferentiationPotential therapeutic strategyInhibitor imatinib mesylateVascular smooth muscle cell phenotypeSmooth muscle cell phenotypeMiR-223 mimicsUptake of platelets
2019
Mitochondrial MsrB2 serves as a switch and transducer for mitophagy
Lee SH, Lee S, Du J, Jain K, Ding M, Kadado AJ, Atteya G, Jaji Z, Tyagi T, Kim W, Herzog RI, Patel A, Ionescu CN, Martin KA, Hwa J. Mitochondrial MsrB2 serves as a switch and transducer for mitophagy. EMBO Molecular Medicine 2019, 11: emmm201910409. PMID: 31282614, PMCID: PMC6685081, DOI: 10.15252/emmm.201910409.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PlateletsCell LineDiabetes MellitusFemaleHumansMethionine Sulfoxide ReductasesMice, Inbred C57BLMice, KnockoutMicrofilament ProteinsMicrotubule-Associated ProteinsMitochondriaMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMitophagyMutationOxidation-ReductionOxidative StressParkinson DiseaseSignal TransductionUbiquitin-Protein LigasesUbiquitinationConceptsReduced mitophagyOxidative stress-induced mitophagyNovel regulatory mechanismStress-induced mitophagyLC3 interactionMitochondrial matrixDamaged mitochondriaMsrB2Reactive oxygen speciesRegulatory mechanismsMethionine oxidationMitophagyMitochondriaPlatelet apoptosisOxygen speciesPlatelet-specific knockoutApoptosisPathophysiological importanceExpressionImportant roleUbiquitinationParkin mutationsParkinSpeciesLC3Age associated non-linear regulation of redox homeostasis in the anucleate platelet: Implications for CVD risk patients
Jain K, Tyagi T, Patell K, Xie Y, Kadado AJ, Lee SH, Yarovinsky T, Du J, Hwang J, Martin KA, Testani J, Ionescu CN, Hwa J. Age associated non-linear regulation of redox homeostasis in the anucleate platelet: Implications for CVD risk patients. EBioMedicine 2019, 44: 28-40. PMID: 31130473, PMCID: PMC6604369, DOI: 10.1016/j.ebiom.2019.05.022.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAge FactorsAgedAged, 80 and overAgingAnimalsAntioxidantsApoptosisBiomarkersBlood PlateletsCardiovascular DiseasesComorbidityDisease Models, AnimalFemaleHomeostasisHumansMaleMiceMiddle AgedOxidation-ReductionOxidative StressPlatelet ActivationPlatelet AdhesivenessReactive Oxygen SpeciesRisk AssessmentRisk FactorsConceptsRisk patientsMouse studiesPlatelet phenotypeMajor adverse cardiovascular eventsHigh cardiovascular risk patientsAdaptive increaseAdverse cardiovascular eventsCentral pathophysiological roleCVD risk patientsCardiovascular risk patientsAggressive antiplatelet therapyEffect of comorbidityAge group 40Young healthy subjectsAntiplatelet therapyCardiovascular eventsYear age cohortAdvanced ageCVD patientsGroup 40Healthy subjectsPathophysiological roleElderly populationCardiovascular pathologyPatientsPlatelet-derived miR-223 promotes a phenotypic switch in arterial injury repair
Zeng Z, Xia L, Fan X, Ostriker AC, Yarovinsky T, Su M, Zhang Y, Peng X, Xie Y, Pi L, Gu X, Chung SK, Martin KA, Liu R, Hwa J, Tang WH. Platelet-derived miR-223 promotes a phenotypic switch in arterial injury repair. Journal Of Clinical Investigation 2019, 129: 1372-1386. PMID: 30645204, PMCID: PMC6391113, DOI: 10.1172/jci124508.Peer-Reviewed Original ResearchConceptsArterial injuryInjury repairMiR-223Intimal hyperplasiaVSMC dedifferentiationArterial injury repairArterial wire injuryPlatelet-derived miRNAsVascular injury repairVSMC phenotypic switchingInjury-induced dedifferentiationMiR-223 mimicsDiabetic miceEndothelial denudationWire injuryReporter miceUptake of GFPInjuryHyperplasiaVSMCsReduced expressionVivo studiesPhenotypic switchMiceSignificant increase
2016
Inducing mitophagy in diabetic platelets protects against severe oxidative stress
Lee SH, Du J, Stitham J, Atteya G, Lee S, Xiang Y, Wang D, Jin Y, Leslie KL, Spollett G, Srivastava A, Mannam P, Ostriker A, Martin KA, Tang WH, Hwa J. Inducing mitophagy in diabetic platelets protects against severe oxidative stress. EMBO Molecular Medicine 2016, 8: 779-795. PMID: 27221050, PMCID: PMC4931291, DOI: 10.15252/emmm.201506046.Peer-Reviewed Original ResearchConceptsDiabetes mellitusOxidative stressThrombotic cardiovascular eventsAnticipation of exposureCardiovascular eventsOxidative stress-mediated mitochondrial damageNormal platelet activationDiabetic plateletsPlatelet functionPlatelet pathologyPlatelet activationSevere oxidative stressNormal plateletsConsiderable mortalityProtective mechanismMitochondrial damageMellitusThrombosisPlateletsMitophagy inductionPhosphorylated p53Mitophagy machineryPlatelets resultsAutophagy processJNK activationThe Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation
Chae WJ, Ehrlich AK, Chan PY, Teixeira AM, Henegariu O, Hao L, Shin JH, Park JH, Tang WH, Kim ST, Maher SE, Goldsmith-Pestana K, Shan P, Hwa J, Lee PJ, Krause DS, Rothlin CV, McMahon-Pratt D, Bothwell AL. The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation. Immunity 2016, 44: 246-258. PMID: 26872695, PMCID: PMC4758884, DOI: 10.1016/j.immuni.2016.01.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, DermatophagoidesAntigens, ProtozoanAsthmaBlood PlateletsCell DifferentiationCells, CulturedCytokinesExtracellular Signal-Regulated MAP KinasesGene Expression RegulationHumansInflammationIntercellular Signaling Peptides and ProteinsLeishmania majorLeishmaniasis, CutaneousMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicModels, AnimalPyroglyphidaeSignal TransductionTh2 CellsTOR Serine-Threonine KinasesWnt ProteinsConceptsCell-mediated inflammationTh2 cell cytokine productionCell cytokine productionLeukocyte-platelet aggregatesLeukocyte infiltrationDkk-1Cytokine productionT helper 2 cellsLeishmania major infectionHouse dust miteTranscription factor c-MafAllergen challengeMajor infectionDust miteImmune responseDickkopf-1Parasitic infectionsGATA-3Pathological roleFunctional inhibitionInflammationC-MafP38 MAPKInfiltrationInfection
2014
Aldose Reductase–Mediated Phosphorylation of p53 Leads to Mitochondrial Dysfunction and Damage in Diabetic Platelets
Tang WH, Stitham J, Jin Y, Liu R, Lee SH, Du J, Atteya G, Gleim S, Spollett G, Martin K, Hwa J. Aldose Reductase–Mediated Phosphorylation of p53 Leads to Mitochondrial Dysfunction and Damage in Diabetic Platelets. Circulation 2014, 129: 1598-1609. PMID: 24474649, PMCID: PMC3989377, DOI: 10.1161/circulationaha.113.005224.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAldehyde ReductaseAnimalsApoptosisBcl-X ProteinBlood PlateletsCarotid Artery DiseasesDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Disease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedMitochondrial DiseasesPhosphorylationSignal TransductionThrombosisTumor Suppressor Protein p53ConceptsMitochondrial dysfunctionHyperglycemia-induced mitochondrial dysfunctionP53 phosphorylationAntiapoptotic protein Bcl-xL.Platelet apoptosisMitochondrial damageMitochondrial membrane potentialReductase activationActivation of p53Reactive oxygen species productionOxygen species productionBcl-xL.Molecular pathwaysSevere mitochondrial damagePhosphorylationNovel therapeutic targetAldose reductase activationSpecies productionMembrane potentialApoptosisCentral roleTherapeutic targetDose-dependent mannerActivationP53