Featured Publications
Fishing for “complements” with vascular organoid models of microvascular disease
Gu S, Yarovinsky T, Hwa J. Fishing for “complements” with vascular organoid models of microvascular disease. Cell Stem Cell 2023, 30: 1285-1286. PMID: 37802032, DOI: 10.1016/j.stem.2023.09.004.Peer-Reviewed Original ResearchPlatelet-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 growthUnfolded 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 inductionInsights into platelet pharmacology from a cryo-EM structure of the ABCC4 transporter
Sharda A, Gu S, Hwa J. Insights into platelet pharmacology from a cryo-EM structure of the ABCC4 transporter. Nature Cardiovascular Research 2023, 2: 606-608. PMID: 37655224, PMCID: PMC10470688, DOI: 10.1038/s44161-023-00293-z.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsLipid 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 ResearchA 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 functionsThrombocytopathy 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 2019SOD2 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
2024
Methionine sulfoxide reductase B2 protects against cardiac complications in diabetes mellitus
Lee S, Cho S, Lee J, Kim J, Kim S, Jeong M, Hong J, Kim G, Lee S, Kim E, Kim J, Kim J, Hwa J, Kim W. Methionine sulfoxide reductase B2 protects against cardiac complications in diabetes mellitus. Diabetology & Metabolic Syndrome 2024, 16: 149. PMID: 38970135, PMCID: PMC11225187, DOI: 10.1186/s13098-024-01390-0.Peer-Reviewed Original ResearchDiabetes mellitusCardiac fibrosisDiabetic cardiomyopathyReactive oxygen speciesAbnormal electrophysiological functionIncreased cardiac fibrosisMethionine sulfoxide reductase B2Chronic metabolic disorderIncreased ROSDiabetic mouse modelCardiac complicationsCardiac damageHeart failureKnockout miceDM miceElectrophysiological functionMouse modelHeart damageMetabolic disordersHistological analysisStructural pathologyCardiac tissueMiceExcessive reactive oxygen speciesHeart samplesNovel strategies for targeting neutrophil against myocardial infarction
Jiang K, Hwa J, Xiang Y. Novel strategies for targeting neutrophil against myocardial infarction. Pharmacological Research 2024, 205: 107256. PMID: 38866263, DOI: 10.1016/j.phrs.2024.107256.Peer-Reviewed Original Research
2023
Multimodality Platelet Evaluation By Mass Cytometry and Genetic Analysis in Patients with Bleeding Disorders
Gu S, Gallagher P, Butt A, Gu V, Lezon-Geyda K, Schulz V, Prozora S, Lee A, Neparidze N, Bar N, Martin K, Cornell J, Chirico G, Chakraborty R, Rinder H, Hwa J, Bona R. Multimodality Platelet Evaluation By Mass Cytometry and Genetic Analysis in Patients with Bleeding Disorders. Blood 2023, 142: 1197. DOI: 10.1182/blood-2023-177946.Peer-Reviewed Original ResearchBleeding tendencyBleeding disorderPlatelet markersPlatelet aggregometryMass cytometryPlatelet functionPlatelet disordersSingle-center prospective studyLow-risk groupAbnormal bleeding tendencyQualitative platelet disordersLarge patient cohortQuantitative platelet disordersCommon underlying causeGenetic variantsMultimodality evaluationTotal patientsRisk stratificationLaboratory suspicionPlatelet dysfunctionProspective studyPatient cohortUnivariate analysisPlatelet volumeRisk groupsPyroptosis in cardiovascular diseases: Pumping gasdermin on the fire
Yarovinsky T, Su M, Chen C, Xiang Y, Tang W, Hwa J. Pyroptosis in cardiovascular diseases: Pumping gasdermin on the fire. Seminars In Immunology 2023, 69: 101809. PMID: 37478801, PMCID: PMC10528349, DOI: 10.1016/j.smim.2023.101809.Peer-Reviewed Original ResearchConceptsPost-translational modificationsAcute cardiovascular eventsChronic cardiovascular diseaseCardiovascular diseaseSmall molecule inhibitorsPyroptosis resultsGenetic toolsGasdermin proteinsWhole organismInflammatory caspasesCardiovascular eventsCell deathMolecule inhibitorsCell typesProteolytic cleavageCellular mechanismsActivation of inflammasomesCardiovascular systemKnockout animalsAmplification of inflammationRole of pyroptosisPro-inflammatory processesDifferent cellsNovel therapeutic approachesPyroptosisThe age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques
Kabir I, Zhang X, Dave J, Chakraborty R, Qu R, Chandran R, Ntokou A, Gallardo-Vara E, Aryal B, Rotllan N, Garcia-Milian R, Hwa J, Kluger Y, Martin K, Fernández-Hernando C, Greif D. The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques. Nature Aging 2023, 3: 64-81. PMID: 36743663, PMCID: PMC9894379, DOI: 10.1038/s43587-022-00342-5.Peer-Reviewed Original ResearchConceptsAtherosclerotic plaquesBone marrowSmooth muscle-derived cellsSMC progenitorsAtherosclerotic plaque cellsSmooth muscle cell progenitorsPredominant risk factorCause of deathNovel therapeutic strategiesTNF receptor 1Muscle-derived cellsAged bone marrowAged BMEffect of agePlaque burdenAged miceRisk factorsTumor necrosisTherapeutic strategiesPlaque cellsMyeloid cellsReceptor 1Integrin β3Cell progenitorsAtherosclerosis
2022
Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis
Su M, Chen C, Li S, Li M, Zeng Z, Zhang Y, Xia L, Li X, Zheng D, Lin Q, Fan X, Wen Y, Liu Y, Chen F, Luo W, Bu Y, Qin J, Guo M, Qiu M, Sun L, Liu R, Wang P, Hwa J, Tang WH. Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis. Nature Cardiovascular Research 2022, 1: 732-747. PMID: 35967457, PMCID: PMC9362711, DOI: 10.1038/s44161-022-00108-7.Peer-Reviewed Original ResearchToll-like receptor 4S100A8/A9Gasdermin DSevere sepsisNeutrophil extracellular trap formationPathology of sepsisRapid clinical deteriorationInflammatory cytokine releaseKey inflammatory cellsExtracellular trap formationGSDMD-deficient miceClinical deteriorationCecal ligationInflammatory cellsInflammatory cytokinesCytokine releaseReceptor 4SepsisExcessive releasePharmacological inhibitionGenetic ablationNET formationPyroptosisSignificant upregulationInflammationHistone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity
Chakraborty R, Ostriker AC, Xie Y, Dave JM, Gamez-Mendez A, Chatterjee P, Abu Y, Valentine J, Lezon-Geyda K, Greif DM, Schulz VP, Gallagher PG, Sessa WC, Hwa J, Martin KA. Histone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity. Circulation 2022, 145: 1720-1737. PMID: 35502657, DOI: 10.1161/circulationaha.121.057599.Peer-Reviewed Original ResearchConceptsHistone acetylationContractile genesContractile protein expressionPhenotypic switchingHistone acetyl transferase p300Human intimal hyperplasiaPlatelet-derived growth factor treatmentAcetyl transferase p300Key regulatory mechanismSmooth muscle cell phenotypeP300 expressionP300-dependent acetylationSmooth muscle plasticityDistinct functional interactionsMuscle cell phenotypeProtein expressionIntimal hyperplasiaRole of p300Methylcytosine dioxygenase TET2Chromatin modificationsEpigenetic regulationVSMC phenotypic switchingSpecific histoneCardiovascular diseaseMaster regulatorSugar, Fat, and YAP: A Recipe for Vascular Stiffness
Mani A, Hwa J, Martin KA. Sugar, Fat, and YAP: A Recipe for Vascular Stiffness. Circulation Research 2022, 130: 868-870. PMID: 35298300, PMCID: PMC9112226, DOI: 10.1161/circresaha.122.320880.Peer-Reviewed Original ResearchGasdermin D inhibition confers antineutrophil mediated cardioprotection in acute myocardial infarction
Jiang K, Tu Z, Chen K, Xu Y, Chen F, Xu S, Shi T, Qian J, Shen L, Hwa J, Wang D, Xiang Y. Gasdermin D inhibition confers antineutrophil mediated cardioprotection in acute myocardial infarction. Journal Of Clinical Investigation 2022, 132: e151268. PMID: 34752417, PMCID: PMC8718151, DOI: 10.1172/jci151268.Peer-Reviewed Original ResearchConceptsAcute myocardial infarctionGasdermin DInfarcted heartMyocardial infarctionBone marrow transplantation studiesAMI mouse modelIL-1β releaseMarrow transplantation studiesReduced heart failureBlood leukocytosisDetrimental immunopathologyEarly mobilizationHeart failureInfarct sizePatient survivalVentricular remodelingCardiac functionAMI survivalMouse modelHeart functionExcessive boneNeutrophil productionNeutrophil generationScar sizePharmacological inhibition
2021
TET2 Protects Against Vascular Smooth Muscle Cell Apoptosis and Intimal Thickening in Transplant Vasculopathy
Ostriker AC, Xie Y, Chakraborty R, Sizer AJ, Bai Y, Ding M, Song WL, Huttner A, Hwa J, Martin KA. TET2 Protects Against Vascular Smooth Muscle Cell Apoptosis and Intimal Thickening in Transplant Vasculopathy. Circulation 2021, 144: 455-470. PMID: 34111946, PMCID: PMC8643133, DOI: 10.1161/circulationaha.120.050553.Peer-Reviewed Original ResearchMeSH KeywordsAllograftsAnimalsApoptosisBiomarkersDioxygenasesDisease Models, AnimalDisease SusceptibilityDNA-Binding ProteinsHeart TransplantationHumansImmunohistochemistryInterferon-gammaMiceMice, KnockoutMyocytes, Smooth MuscleSignal TransductionSTAT1 Transcription FactorTunica IntimaVascular DiseasesConceptsCoronary allograft vasculopathyGraft arteriopathyIntimal thickeningCAV progressionRole of TET2VSMC apoptosisTransplant samplesGraft modelHigh-dose ascorbic acidTET2 expressionVSMC phenotypeContext of transplantCoronary blood flowEffect of IFNγTET2 activityTET2 depletionSmooth muscle cell apoptosisVascular smooth muscle cell apoptosisMuscle cell apoptosisAllograft vasculopathyDevastating sequelaeMedial thinningAortic graftHeart transplantTransplant failureLiver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy
McConnell MJ, Kawaguchi N, Kondo R, Sonzogni A, Licini L, Valle C, Bonaffini PA, Sironi S, Alessio MG, Previtali G, Seghezzi M, Zhang X, Lee A, Pine AB, Chun HJ, Zhang X, Fernandez-Hernando C, Qing H, Wang A, Price C, Sun Z, Utsumi T, Hwa J, Strazzabosco M, Iwakiri Y. Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy. Journal Of Hepatology 2021, 75: 647-658. PMID: 33991637, PMCID: PMC8285256, DOI: 10.1016/j.jhep.2021.04.050.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsLiver injuryInterleukin-6Sinusoidal endothelial cellsAlanine aminotransferaseLiver histologyD-dimerCOVID-19Primary human liver sinusoidal endothelial cellsSARS-CoV-2 infectionHuman liver sinusoidal endothelial cellsEndothelial cellsSoluble glycoprotein 130IL-6 levelsSmall-interfering RNA knockdownJAK inhibitor ruxolitinibFactor VIII activityProinflammatory factorsInflammatory signalsLarge cohortInhibitor ruxolitinibVWF antigenEndotheliopathyPatientsInjury