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 ResearchConceptsCD8 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 growthAltered expression of platelet proteins and calpain activity mediate hypoxia-induced prothrombotic phenotype
Tyagi T, Ahmad S, Gupta N, Sahu A, Ahmad Y, Nair V, Chatterjee T, Bajaj N, Sengupta S, Ganju L, Singh SB, Ashraf MZ. Altered expression of platelet proteins and calpain activity mediate hypoxia-induced prothrombotic phenotype. Blood 2013, 123: 1250-1260. PMID: 24297866, DOI: 10.1182/blood-2013-05-501924.Peer-Reviewed Original ResearchConceptsCalpain activityPlatelet reactivityProthrombotic phenotypeThrombus formationSoluble P-selectin levelsIncidence of thrombosisP-selectin levelsProthrombotic rolePlatelet hyperreactivitySolid tumorsVivo modelSmall subunit 1ThrombosisPathological conditionsAltered expressionHypoxic conditionsHypoxic environmentPlatelet proteinsHypoxiaExtreme altitudePresent studyCalpain functionPlateletsSubunit 1Phenotype
2022
Unfolded Protein Response Differentially Modulates the Platelet Phenotype
Jain K, Tyagi T, Du J, Hu X, Patell K, Martin KA, Hwa J. Unfolded Protein Response Differentially Modulates the Platelet Phenotype. Circulation Research 2022, 131: 290-307. PMID: 35862006, PMCID: PMC9357223, DOI: 10.1161/circresaha.121.320530.Peer-Reviewed Original ResearchConceptsUPR pathwayProtein responseMouse plateletsUnfolded protein responseActivation of UPRPlatelet phenotypeTranscriptional regulationGenomic regulationProtein misfoldingAnucleate plateletsProtein aggregationUPR activationPhosphorylation of PLCγ2Chemical chaperonesXBP1 pathwayP38 MAPKPERK pathwayUPRPKCδ activationPlatelet physiologyActivation pathwayPathwayPhenotypeIRE1α inhibitionSelective induction
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 TransductionUbiquitinationUbiquitin-Protein LigasesConceptsReduced 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 pathologyPatientsEpithelial (E)-Cadherin is a Novel Mediator of Platelet Aggregation and Clot Stability
Scanlon VM, Teixeira AM, Tyagi T, Zou S, Zhang PX, Booth CJ, Kowalska MA, Bao J, Hwa J, Hayes V, Marks MS, Poncz M, Krause DS. Epithelial (E)-Cadherin is a Novel Mediator of Platelet Aggregation and Clot Stability. Thrombosis And Haemostasis 2019, 119: 744-757. PMID: 30861547, PMCID: PMC6599679, DOI: 10.1055/s-0039-1679908.Peer-Reviewed Original ResearchConceptsConditional knockout miceKnockout micePlatelet aggregationE-cadherinClot stabilityClot stabilizationSynthase kinase 3β activationAntibody-mediated platelet depletionVivo injury modelsNull plateletsPlatelet productionWild-type miceTail bleeding timeAkt/GSK3βMurine platelet aggregationKnockout mouse modelPlatelet dysfunctionFibrin depositionInjury modelPlatelet depletionPrimary human plateletsBleeding timeMouse modelPlatelet numberE-cadherin antibody
2017
MicroRNA-145 Impedes Thrombus Formation via Targeting Tissue Factor in Venous Thrombosis
Sahu A, Jha P, Prabhakar A, Singh H, Gupta N, Chatterjee T, Tyagi T, Sharma S, Kumari B, Singh S, Nair V, Goel S, Ashraf M. MicroRNA-145 Impedes Thrombus Formation via Targeting Tissue Factor in Venous Thrombosis. EBioMedicine 2017, 26: 175-186. PMID: 29217135, PMCID: PMC5832640, DOI: 10.1016/j.ebiom.2017.11.022.Peer-Reviewed Original ResearchConceptsMiR-145 levelsTissue factorVenous thromboembolismMiR-145Thrombus formationTF levelsTargeting tissue factorPromising therapeutic strategyCardiovascular complicationsThrombus loadVenous thrombosisCoagulation variablesPreclinical findingsTherapeutic strategiesVT patientsTF expressionInverse correlationKey moleculesPatientsVivo experimentsUndescribed roleTarget genesVTThromboembolismLevelsActivation of NLRP3 inflammasome complex potentiates venous thrombosis in response to hypoxia
Gupta N, Sahu A, Prabhakar A, Chatterjee T, Tyagi T, Kumari B, Khan N, Nair V, Bajaj N, Sharma M, Ashraf MZ. Activation of NLRP3 inflammasome complex potentiates venous thrombosis in response to hypoxia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 4763-4768. PMID: 28420787, PMCID: PMC5422823, DOI: 10.1073/pnas.1620458114.Peer-Reviewed Original ResearchConceptsExpression of NLRP3Venous thrombosisVenous thromboembolismIL-1βCaspase-1Activation of NLRP3Acute thrombotic eventsHypoxic conditionsIL-1β secretionNLRP3 inflammasome complexHypoxia-inducible factorThromboembolic eventsProinflammatory stateSystemic hypoxiaThrombotic eventsPreclinical findingsAltered hemostasisRisk factorsCardiovascular conditionsCommon causeInflammasome activationThrombosisHealthy individualsPyrin domainHIF-1α
2015
Polysulfated Trehalose as a Novel Anticoagulant Agent with Dual Mode of Action
Rashid Q, Abid M, Gupta N, Tyagi T, Ashraf M, Jairajpuri M. Polysulfated Trehalose as a Novel Anticoagulant Agent with Dual Mode of Action. BioMed Research International 2015, 2015: 630482. PMID: 25866798, PMCID: PMC4381846, DOI: 10.1155/2015/630482.Peer-Reviewed Original ResearchConceptsFavorable safety profileNovel anticoagulant agentsForm of heparinAnticoagulant administrationSafety profileAntithrombotic agentsAnticoagulant agentsAnticoagulant factorsHemostatic balanceAntithrombotic potentialLow doseAntiplatelet mechanismFibrinolytic systemPlatelet aggregationThrombotic ratsFirst lineHeparinCoagulation timeRatsBlood plasmaNovel compoundsThromboembolismComplicationsAnticoagulantsTherapy