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 1PhenotypeA guide to molecular and functional investigations of platelets to bridge basic and clinical sciences
Tyagi T, Jain K, Gu S, Qiu M, Gu V, Melchinger H, Rinder H, Martin K, Gardiner E, Lee A, Tang W, Hwa J. A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences. Nature Cardiovascular Research 2022, 1: 223-237. PMID: 37502132, PMCID: PMC10373053, DOI: 10.1038/s44161-022-00021-z.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsVascular smooth muscle cellsPlatelet functional assaysCoronavirus disease 2019Smooth muscle cellsImmune cellsImmune regulationVascular remodelingDisease 2019Pathophysiological processesTranslational relevancePatient diagnosisFlow cytometryMuscle cellsPlatelet biologyFunctional assaysPlatelet investigationsHomeostatic processesPlateletsPhenotypic heterogeneityFunctional stateClinical scienceCellsAdditional roleThrombosisSuch diverse functions
2024
Platelet 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
2023
Lipid remodeling in megakaryocyte differentiation and platelet biogenesis
Jain K, Tyagi T, Hwa J. Lipid remodeling in megakaryocyte differentiation and platelet biogenesis. Nature Cardiovascular Research 2023, 2: 803-804. PMID: 37736249, PMCID: PMC10512809, DOI: 10.1038/s44161-023-00324-9.Peer-Reviewed Original Research
2022
Platelet in thrombo-inflammation: Unraveling new therapeutic targets
Sharma S, Tyagi T, Antoniak S. Platelet in thrombo-inflammation: Unraveling new therapeutic targets. Frontiers In Immunology 2022, 13: 1039843. PMID: 36451834, PMCID: PMC9702553, DOI: 10.3389/fimmu.2022.1039843.Peer-Reviewed Original ResearchConceptsRole of plateletsViral infectionPlatelet activationCoagulation pathwayThrombo-inflammatory disordersAcute ischemic strokeContribution of plateletsAnti-inflammatory potentialThrombo-inflammatory diseasesCoronavirus disease 2019Sickle cell diseaseNon-pathologic conditionsNew therapeutic targetsRecruitment of leukocytesPathologic platelet activationPlatelet surface receptorsFormation of thrombiInitial platelet activationSuperficial thrombophlebitisAntiphospholipid syndromeIschemic strokeMicrovascular thrombosisClinical manifestationsInflammatory processCell diseaseUnfolded 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 inductionHigh-multiplexing quantitative CodePlex proteomic profiling of platelets in triple-negative breast cancer (TNBC) patients and healthy subjects.
Han E, Gu S, Steinle M, Gu V, Tyagi T, Mackay S, Hwa J, Zhou J. High-multiplexing quantitative CodePlex proteomic profiling of platelets in triple-negative breast cancer (TNBC) patients and healthy subjects. Journal Of Clinical Oncology 2022, 40: e15017-e15017. DOI: 10.1200/jco.2022.40.16_suppl.e15017.Peer-Reviewed Original ResearchTriple-negative breast cancerTriple-negative breast cancer patientsBreast cancer patientsCancer patientsHealthy controlsIL-8IL-9TNBC patientsPilot studyNegative breast cancer patientsAberrant platelet activationPlatelet releasateDifferential cytokine profilesPlatelet lysateNegative breast cancerSmall pilot studySerum/plasmaImmune panelMinimal IFNIL-17AMIP-1aCytokine profileIL-10IL-15Healthy patients
2020
Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation
Gu SX, Tyagi T, Jain K, Gu VW, Lee SH, Hwa JM, Kwan JM, Krause DS, Lee AI, Halene S, Martin KA, Chun HJ, Hwa J. Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation. Nature Reviews Cardiology 2020, 18: 194-209. PMID: 33214651, PMCID: PMC7675396, DOI: 10.1038/s41569-020-00469-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAdministration, InhalationAnticoagulantsBlood Coagulation DisordersBlood Platelet DisordersCOVID-19COVID-19 Drug TreatmentEndothelium, VascularEndothelium-Dependent Relaxing FactorsEpoprostenolHeart Disease Risk FactorsHumansIloprostInflammationNitric OxidePlatelet Aggregation InhibitorsSARS-CoV-2Systemic Inflammatory Response SyndromeThrombosisThrombotic MicroangiopathiesVascular DiseasesVasodilator AgentsVenous ThromboembolismConceptsCardiovascular risk factorsRisk factorsCOVID-19Severe acute respiratory syndrome coronavirus 2Pre-existing cardiovascular diseaseAcute respiratory syndrome coronavirus 2Traditional cardiovascular risk factorsAcute respiratory distress syndromeRespiratory syndrome coronavirus 2Respiratory distress syndromeManagement of patientsSyndrome coronavirus 2COVID-19 pathologyCoronavirus disease 2019Potential therapeutic strategyCytokine stormEndothelial dysfunctionThrombotic complicationsDistress syndromeExcessive inflammationCoronavirus 2Severe outcomesAdvanced ageCardiovascular diseaseDisease 2019“CO”ping With a Sticky Situation
Jain K, Tyagi T, Hwa J. “CO”ping With a Sticky Situation. Arteriosclerosis Thrombosis And Vascular Biology 2020, 40: 2344-2345. PMID: 32966131, PMCID: PMC7517721, DOI: 10.1161/atvbaha.120.315158.Commentaries, Editorials and Letters
2019
Venous thrombosis at altitude presents with distinct biochemical profiles: a comparative study from the Himalayas to the plains
Prabhakar A, Chatterjee T, Bajaj N, Tyagi T, Sahu A, Gupta N, Kumari B, Nair V, Kumar B, Ashraf MZ. Venous thrombosis at altitude presents with distinct biochemical profiles: a comparative study from the Himalayas to the plains. Blood Advances 2019, 3: 3713-3723. PMID: 31765479, PMCID: PMC6880906, DOI: 10.1182/bloodadvances.2018024554.Peer-Reviewed Original ResearchConceptsVenous thromboembolismAdhesion molecule-1VTE patientsHA exposureMolecule-1Vascular cell adhesion molecule-1Toll-like receptor 2Intracellular adhesion molecule-1Receiver operator characteristic curve analysisCell adhesion molecule-1Operator characteristic curve analysisMost VTEElevated platelet countVascular endothelial growth factorCharacteristic curve analysisYounger age groupsPlatelet factor 4Endothelial growth factorDistinct biochemical profilesVon Willebrand factorAltered coagulationVTE eventsVenous thrombosisEndothelial activationPlatelet countRole of Platelet Mitochondria: Life in a Nucleus-Free Zone
Melchinger H, Jain K, Tyagi T, Hwa J. Role of Platelet Mitochondria: Life in a Nucleus-Free Zone. Frontiers In Cardiovascular Medicine 2019, 6: 153. PMID: 31737646, PMCID: PMC6828734, DOI: 10.3389/fcvm.2019.00153.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsTranscriptional regulationAvian thrombocytesMammalian plateletsMorphological flexibilityAerobic respirationStress responseMitochondriaPlatelet mitochondriaMitochondria damageProtein expressionCritical roleMetabolic substratesPlatelet lifespanKey roleInjury responseCirculating cellsPathophysiological roleNucleusCellsOrganellesRoleRNAStressSurvivalRegulationAuthor's response to “platelet antioxidants: A conundrum in aging”
Jain K, Tyagi T, Ionescu CN, Hwa J. Author's response to “platelet antioxidants: A conundrum in aging”. EBioMedicine 2019, 47: 31-32. PMID: 31471267, PMCID: PMC6796587, DOI: 10.1016/j.ebiom.2019.08.047.Peer-Reviewed Original ResearchCELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation
Esteghamat F, Broughton JS, Smith E, Cardone R, Tyagi T, Guerra M, Szabó A, Ugwu N, Mani MV, Azari B, Kayingo G, Chung S, Fathzadeh M, Weiss E, Bender J, Mane S, Lifton RP, Adeniran A, Nathanson MH, Gorelick FS, Hwa J, Sahin-Tóth M, Belfort-DeAguiar R, Kibbey RG, Mani A. CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation. Nature Genetics 2019, 51: 1233-1243. PMID: 31358993, PMCID: PMC6675645, DOI: 10.1038/s41588-019-0470-3.Peer-Reviewed Original ResearchConceptsEarly-onset atherosclerosisMetabolic syndromeMetabolic syndrome traitsWhole-exome sequence analysisAttractive therapeutic targetPlatelet hyperactivationInsulin levelsPlasma insulinPlasma levelsInsulin sensitivityInsulin secretionTherapeutic targetPlatelet activationDisease mechanismsSyndrome traitsAtherosclerosisFunction mutationsSyndromeNovel lossInsulinMutationsSecretionMitochondrial 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
2018
Genome-Wide Expression Analysis Suggests Hypoxia-Triggered Hyper-Coagulation Leading to Venous Thrombosis at High Altitude
Jha PK, Sahu A, Prabhakar A, Tyagi T, Chatterjee T, Arvind P, Nair J, Gupta N, Kumari B, Nair V, Bajaj N, Shanker J, Sharma M, Kumar B, Ashraf MZ. Genome-Wide Expression Analysis Suggests Hypoxia-Triggered Hyper-Coagulation Leading to Venous Thrombosis at High Altitude. Thrombosis And Haemostasis 2018, 118: 1279-1295. PMID: 29864786, DOI: 10.1055/s-0038-1657770.Peer-Reviewed Original ResearchMeSH KeywordsAdultAltitudeBlood CoagulationBlood Coagulation DisordersCase-Control StudiesGene Expression ProfilingGene Regulatory NetworksGene-Environment InteractionGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansHypoxiaMalePhenotypeRisk AssessmentRisk FactorsTranscriptomeVenous ThrombosisConceptsDeep vein thrombosisGenome-wide expression analysisDifferential expressionVenous thromboembolismEnrichment of genesGenes/pathwaysGene expression profilesHypoxia-responsive genesGene expression profilingRisk factorsGene OntologyOnset of VTEBioinformatics analysisExpression analysisExpression profilingExpression profilesPathway analysisMolecular mechanismsAdditional risk factorsQuantitative reverse transcription polymerase chain reactionReverse transcription-polymerase chain reactionPathophysiology of DVTCommon cardiovascular diseaseRelevant pathwaysGenes
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