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
Phenotypic and genotypic evaluation of bleeding diagnostic dilemmas: Two case studies
Gu S, Butt A, Schulz V, Rinder H, Lee A, Gallagher P, Hwa J, Bona R. Phenotypic and genotypic evaluation of bleeding diagnostic dilemmas: Two case studies. Blood Cells Molecules And Diseases 2024, 110: 102893. PMID: 39260211, DOI: 10.1016/j.bcmd.2024.102893.Peer-Reviewed Original ResearchInherited platelet disordersClinically significant bleedingCases of patientsHeterogeneous group of conditionsGroup of conditionsSignificant bleedingDiagnostic yieldDiagnostic dilemmaPlatelet disordersBleeding disordersEvaluating patientsPatient cohortMolecular pathogenesisMass cytometryHeterogeneous groupPatientsMultimodal approachBleedingImprove patient careDiagnosisDisordersPatient careGenetic sequencesLaboratory testing approachPotential utilityHigh-Dimensional Single-Cell Mass Cytometry Demonstrates Differential Platelet Functional Phenotypes in Infants With Congenital Heart Disease.
Gu S, Marcus B, Gu V, Varghese A, Hwa J, Faustino E. High-Dimensional Single-Cell Mass Cytometry Demonstrates Differential Platelet Functional Phenotypes in Infants With Congenital Heart Disease. Arteriosclerosis Thrombosis And Vascular Biology 2024 PMID: 39171400, DOI: 10.1161/atvbaha.124.321131.Peer-Reviewed Original ResearchCongenital heart diseaseNon-CHD controlsSubpopulation of plateletsCytokine analysisAssociated with congenital heart diseaseSurface markersPlatelet activationHeart diseaseAssociated with hematological abnormalitiesChildren's Heart CenterPlasma cytokine analysisComplex heart defectsBlood of infantsThrombotic vascular complicationsIL (interleukin)-6Cell surface markersDecreased platelet activationMass cytometry approachPlatelet surface markersHypogranular plateletsHeart defectsBleeding eventsPlasma cytokinesPlatelet function phenotypesInflammatory markersEarly thrombus formation is required of eccentric and heterogenous neointimal hyperplasia under disturbed flow
Bai H, Li Z, Zhang W, Thaxton C, Ohashi Y, Gonzalez L, Kano M, Yatsula B, Hwa J, Dardik A. Early thrombus formation is required of eccentric and heterogenous neointimal hyperplasia under disturbed flow. Journal Of Thrombosis And Haemostasis 2024 PMID: 39173878, DOI: 10.1016/j.jtha.2024.07.028.Peer-Reviewed Original ResearchEndothelial cell lossArteriovenous fistulaSmooth muscle cellsNeointimal hyperplasiaHeterogeneous neointimaCell lossThrombus formationMT/mG reporter miceHuman arteriovenous fistulaeInhibit neointimal hyperplasiaEarly thrombus formationAntiplatelet therapyC57BL/6 miceReporter miceAVF failureWistar ratsVenous systemJuxta-anastomotic areaMuscle cellsAnimal modelsVenous outflowEarly thrombusEndothelial cellsArterial inflowThrombusMethionine 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 ResearchAbstract 2121: SUV39H1 Mediated Regulation Of KLF4 And KDM4a Coordinate Smooth Muscle Cell Phenotypic Plasticity
Chatterjee P, Chakraborty R, Sizer A, Xie Y, Hwa J, Martin K. Abstract 2121: SUV39H1 Mediated Regulation Of KLF4 And KDM4a Coordinate Smooth Muscle Cell Phenotypic Plasticity. Arteriosclerosis Thrombosis And Vascular Biology 2024, 44: a2121-a2121. DOI: 10.1161/atvb.44.suppl_1.2121.Peer-Reviewed Original ResearchRNA-seqPhenotypic plasticityEpigenetic regulationH3K9me3 repressive marksRNA-seq transcriptomicsContractile genesEpigenetic transcriptional repressionCell phenotypic plasticityH3K9me3 markExpression of SUV39H1Repressive marksTranscriptional repressionChromatin immunoprecipitationHistone methyltransferaseDedifferentiation in vitroIn vivoSUV39H1 knockdownH3K9me3MRNA stabilitySUV39H1Gene expressionPlasticity of vascular smooth muscle cellsRegulation of Klf4GenesH3K9me3 expression
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
Plasma Proteomic Profiling Illustrates Endothelial and Complement Signature in Patients with Alcohol-Associated Cirrhosis
Allen C, Butt A, Zhao X, Li F, Bahel P, Chang C, Chun H, Gu S, Hwa J, Jakab S, Chen B, Garcia-Tsao G, Rinder H, To U, McConnell M, Lee A, Pine A. Plasma Proteomic Profiling Illustrates Endothelial and Complement Signature in Patients with Alcohol-Associated Cirrhosis. Blood 2022, 140: 8382-8383. DOI: 10.1182/blood-2022-162633.Peer-Reviewed Original ResearchGasdermin 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 upregulationInflammation