2023
Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation
Freitas-Andrade M, Comin C, Van Dyken P, Ouellette J, Raman-Nair J, Blakeley N, Liu Q, Leclerc S, Pan Y, Liu Z, Carrier M, Thakur K, Savard A, Rurak G, Tremblay M, Salmaso N, da F. Costa L, Coppola G, Lacoste B. Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation. Nature Communications 2023, 14: 4965. PMID: 37587100, PMCID: PMC10432480, DOI: 10.1038/s41467-023-40682-3.Peer-Reviewed Original ResearchConceptsHigh mobility group box 1Blood-brain barrierGroup box 1Brain blood vesselsMouse cortical astrocytesPostnatal brain developmentAstroglial factorsNeurovascular couplingAstrocyte morphogenesisCortical astrocytesPostnatal weekAdult miceBox 1Aquaporin-4Endothelial ultrastructureAstrocyte morphologyNeuronal functionAstrocytesBrain developmentTranscriptional changesHMGB1Blood vesselsBirthAlters distributionImportant playersUrothelial Oxidative Stress and ERK Activation Mediate HMGB1-Induced Bladder Pain
Ye S, Mahmood D, Ma F, Leng L, Bucala R, Vera P. Urothelial Oxidative Stress and ERK Activation Mediate HMGB1-Induced Bladder Pain. Cells 2023, 12: 1440. PMID: 37408274, PMCID: PMC10217556, DOI: 10.3390/cells12101440.Peer-Reviewed Original ResearchConceptsHigh mobility group box 1Macrophage migration inhibitory factorBladder painOxidative stressDisulfide HMGB1Mobility group box 1MIF-deficient miceNovel potential therapeutic strategyMigration inhibitory factorGroup box 1Potential therapeutic strategyOxidative stress productionN-acetylcysteine amideERK activationIntravesical treatmentMicturition volumeMicturition parametersReceptor 4Mechanical thresholdPainTherapeutic strategiesBox 1Bladder tissueInhibitory factorWestern blot
2022
HMGB1-mediated restriction of EPO signaling contributes to anemia of inflammation
Dulmovits BM, Tang Y, Papoin J, He M, Li J, Yang H, Addorisio ME, Kennedy L, Khan M, Brindley E, Ashley RJ, Ackert-Bicknell C, Hale J, Kurita R, Nakamura Y, Diamond B, Barnes BJ, Hermine O, Gallagher PG, Steiner LA, Lipton JM, Taylor N, Mohandas N, Andersson U, Al-Abed Y, Tracey KJ, Blanc L. HMGB1-mediated restriction of EPO signaling contributes to anemia of inflammation. Blood 2022, 139: 3181-3193. PMID: 35040907, PMCID: PMC9136881, DOI: 10.1182/blood.2021012048.Peer-Reviewed Original ResearchMeSH KeywordsAnemiaAnimalsErythropoiesisErythropoietinHMGB1 ProteinInflammationMiceReceptors, ErythropoietinSepsisConceptsAnemia of inflammationDamage-associated molecular pattern moleculesHigh-mobility group box 1 proteinMobility group box 1 proteinErythroid precursorsGroup box 1 proteinAdvanced glycation end productsAnti-HMGB1 antibodyGlycation end productsMolecular pattern moleculesChronic phaseSepsis onsetChronic diseasesHMGB1 receptorsAnemia developmentPattern moleculesAnemiaGenetic ablationInflammationMurine precursorRefractory stateHMGB1Reduced expansionEPO signalingDeleterious effectsShort‐Term Safety of Repeated Acetaminophen Use in Patients With Compensated Cirrhosis
McGill MR, James LP, McCullough SS, Moran JH, Mathews SE, Peterson EC, Fleming DP, Tripod ME, Vazquez JH, Kennon‐McGill S, Spencer HJ, Dranoff JA. Short‐Term Safety of Repeated Acetaminophen Use in Patients With Compensated Cirrhosis. Hepatology Communications 2022, 6: 361-373. PMID: 34558847, PMCID: PMC8793989, DOI: 10.1002/hep4.1810.Peer-Reviewed Original ResearchConceptsAPAP-protein adductsAcetaminophen useCirrhosis groupClinical outcomesDay 5Sensitive biomarkerAdverse clinical outcomesShort-term administrationCompensated cirrhosisLiver injuryAPAP administrationLiver damagePK analysisCurrent guidelinesStudy initiationCirrhosisTerm safetyDay 1Day 3APAP metabolitesHigh dosesPatientsPilot studyAPAPLonger treatment
2021
Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain
Ye S, Ma F, Mahmood DFD, Meyer-Siegler KL, Menard RE, Hunt DE, Leng L, Bucala R, Vera PL. Intravesical CD74 and CXCR4, macrophage migration inhibitory factor (MIF) receptors, mediate bladder pain. PLOS ONE 2021, 16: e0255975. PMID: 34424927, PMCID: PMC8382170, DOI: 10.1371/journal.pone.0255975.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorHigh mobility group box 1Bladder painMIF receptorHMGB1 releaseBladder hyperalgesiaMobility group box 1MIF receptor CD74Migration inhibitory factorGroup box 1Primary urothelial cellsInhibitory factor receptorWarrants further investigationCD74 receptorReceptor CD74Micturition parametersReceptor antagonistReceptor 4Box 1PainInhibitory factorHyperalgesiaCD74Urothelial cellsNovel target
2020
Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection
Wei J, Alfajaro MM, DeWeirdt PC, Hanna RE, Lu-Culligan WJ, Cai WL, Strine MS, Zhang SM, Graziano VR, Schmitz CO, Chen JS, Mankowski MC, Filler RB, Ravindra NG, Gasque V, de Miguel FJ, Patil A, Chen H, Oguntuyo KY, Abriola L, Surovtseva YV, Orchard RC, Lee B, Lindenbach BD, Politi K, van Dijk D, Kadoch C, Simon MD, Yan Q, Doench JG, Wilen CB. Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection. Cell 2020, 184: 76-91.e13. PMID: 33147444, PMCID: PMC7574718, DOI: 10.1016/j.cell.2020.10.028.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsCell LineChlorocebus aethiopsClustered Regularly Interspaced Short Palindromic RepeatsCoronavirusCoronavirus InfectionsCOVID-19Gene Knockout TechniquesGene Regulatory NetworksGenome-Wide Association StudyHEK293 CellsHMGB1 ProteinHost-Pathogen InteractionsHumansSARS-CoV-2Vero CellsVirus InternalizationConceptsSARS-CoV-2 infectionSARS-CoV-2Vesicular stomatitis virusGenome-wide CRISPR screenSWI/SNF chromatinSARS-CoV-2 host factorsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionTherapeutic targetHost factorsCoronavirus disease 2019 (COVID-19) pathogenesisSyndrome coronavirus 2 infectionCRISPR screensHost genesGene productsMiddle East respiratory syndrome CoVCoronavirus 2 infectionGenetic hitsHuman cellsSARS-CoV-2 spikeNovel therapeutic targetPotential therapeutic targetVero E6 cellsSARS-CoV-1Small molecule antagonistsStructural basis for the activation and suppression of transposition during evolution of the RAG recombinase
Zhang Y, Corbett E, Wu S, Schatz DG. Structural basis for the activation and suppression of transposition during evolution of the RAG recombinase. The EMBO Journal 2020, 39: embj2020105857. PMID: 32945578, PMCID: PMC7604617, DOI: 10.15252/embj.2020105857.Peer-Reviewed Original ResearchConceptsTarget site DNASite DNARAG1/RAG2 recombinaseSuppression of transpositionCryo-electron microscopyStrand transfer complexAntigen receptor genesDomesticated transposaseTarget DNARAG recombinaseEvolutionary adaptationPaste transpositionStructural basisTransposition activityMechanistic principlesFunctional assaysTransposon endDNAReceptor geneBase unstackingDomesticationTransposaseRecombinaseAdaptive immunityFinal stepHMGB1 Is a Therapeutic Target and Biomarker in Diazepam-Refractory Status Epilepticus with Wide Time Window
Zhao J, Zheng Y, Liu K, Chen J, Lai N, Fei F, Shi J, Xu C, Wang S, Nishibori M, Wang Y, Chen Z. HMGB1 Is a Therapeutic Target and Biomarker in Diazepam-Refractory Status Epilepticus with Wide Time Window. Neurotherapeutics 2020, 17: 710-721. PMID: 31802434, PMCID: PMC7283397, DOI: 10.1007/s13311-019-00815-3.Peer-Reviewed Original ResearchConceptsHigh mobility group box 1Anti-HMGB1 mAbStatus epilepticusTherapeutic targetLife-threatening neurological emergencyToll-like receptor 4 (TLR4)-dependent pathwayAnti-HMGB1 monoclonal antibodyNeutralization of HMGB1Plasma HMGB1 levelsMobility group box 1Severity of seizure activityExogenous high mobility group box 1Incidence of SENonrefractory SEHMGB1 levelsPredictive biomarkersTherapeutic responseNeurological emergencyTherapeutic windowBox 1Seizure activityMonoclonal antibodiesPharmacological therapeuticsSE periodEpilepticus
2019
Extracorporeal photochemotherapy induces bona fide immunogenic cell death
Tatsuno K, Yamazaki T, Hanlon D, Han P, Robinson E, Sobolev O, Yurter A, Rivera-Molina F, Arshad N, Edelson RL, Galluzzi L. Extracorporeal photochemotherapy induces bona fide immunogenic cell death. Cell Death & Disease 2019, 10: 578. PMID: 31371700, PMCID: PMC6675789, DOI: 10.1038/s41419-019-1819-3.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAntigens, NeoplasmApoptosisCD8-Positive T-LymphocytesCell DifferentiationCell Line, TumorCell SurvivalDendritic CellsHMGB1 ProteinHumansImmunogenic Cell DeathLeukocytesLymphoma, T-Cell, CutaneousMethoxsalenMiceMonocytesPhotopheresisPhotosensitizing AgentsReceptor, Interferon alpha-betaUltraviolet RaysConceptsHigh mobility group box 1Tumor-associated antigensCutaneous T-cell lymphomaWhite blood cellsDendritic cellsImmunostimulatory signalsI interferonBona fide immunogenic cell deathMobility group box 1Such dendritic cellsSyngeneic immunocompetent miceCancer cellsT-cell lymphomaType I IFN receptorGroup box 1Immunogenic cell deathI IFN receptorATP-degrading enzymeSecretion of ATPMelanoma cell viabilityCognate immunityUVA irradiationAnticancer immunityImmunocompetent miceCalreticulin exposurePlasma mitochondrial DNA is associated with extrapulmonary sarcoidosis
Ryu C, Brandsdorfer C, Adams T, Hu B, Kelleher DW, Yaggi M, Manning EP, Walia A, Reeves B, Pan H, Winkler J, Minasyan M, Dela Cruz CS, Kaminski N, Gulati M, Herzog EL. Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis. European Respiratory Journal 2019, 54: 1801762. PMID: 31273041, PMCID: PMC8088542, DOI: 10.1183/13993003.01762-2018.Peer-Reviewed Original ResearchConceptsExtrapulmonary diseaseMitochondrial DNAExtracellular mtDNABAL fluidAlpha-1 antitrypsin deficiencyPlasma mitochondrial DNAPlasma of patientsAfrican AmericansExtrapulmonary sarcoidosisSarcoidosis cohortSarcoidosis subjectsScadding stageAfrican American descentClinical featuresClinical findingsGranulomatous diseaseHealthy controlsAntitrypsin deficiencyGenomic researchHigher oddsSarcoidosisAggressive phenotypeMechanistic basisDiseaseTherapeutic insights
2018
Excess glucose induce trophoblast inflammation and limit cell migration through HMGB1 activation of Toll‐Like receptor 4
Heim KR, Mulla MJ, Potter JA, Han CS, Guller S, Abrahams VM. Excess glucose induce trophoblast inflammation and limit cell migration through HMGB1 activation of Toll‐Like receptor 4. American Journal Of Reproductive Immunology 2018, 80: e13044. PMID: 30175447, DOI: 10.1111/aji.13044.Peer-Reviewed Original ResearchConceptsToll-like receptor 4High mobility group box 1Damage-associated molecular patternsHMGB1 activationIL-1βIL-8Trophoblast responsesReceptor 4Human first trimester trophoblast cell lineFirst trimester trophoblast cell lineInflammatory IL-8Risk of preeclampsiaGroup box 1Uric acidIL-1β responseExcess glucoseTrophoblast cell lineCell migrationTrophoblast inflammationPregnancy outcomesTLR4 antagonistLPS-RSIL-6SFlt-1HMGB1 inhibitor
2015
Single-molecule analysis of RAG-mediated V(D)J DNA cleavage
Lovely GA, Brewster RC, Schatz DG, Baltimore D, Phillips R. Single-molecule analysis of RAG-mediated V(D)J DNA cleavage. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e1715-e1723. PMID: 25831509, PMCID: PMC4394307, DOI: 10.1073/pnas.1503477112.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesSingle-molecule assaysSame DNA moleculeAntigen receptor genesConsensus recombination signal sequencesSingle-molecule analysisHigh mobility group box protein 1Individual molecular eventsSignal sequenceSingle-molecule levelGene productsDNA bindingMolecular eventsLymphocyte developmentDNA moleculesDNA cleavageProtein 1Synapse formationSynaptic complexReceptor geneCleavageRAGAssaysRAG1/2Complexes
2014
The architecture of the 12RSS in V(D)J recombination signal and synaptic complexes
Ciubotaru M, Surleac MD, Metskas LA, Koo P, Rhoades E, Petrescu AJ, Schatz DG. The architecture of the 12RSS in V(D)J recombination signal and synaptic complexes. Nucleic Acids Research 2014, 43: 917-931. PMID: 25550426, PMCID: PMC4333397, DOI: 10.1093/nar/gku1348.Peer-Reviewed Original ResearchGSK3β-dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury
Park D, Jiang S, Liu Y, Siegal G, Inoki K, Abraham E, Zmijewski J. GSK3β-dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2014, 307: l735-l745. PMID: 25239914, PMCID: PMC4233296, DOI: 10.1152/ajplung.00165.2014.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAMP-Activated Protein KinasesAnimalsCell LineChemokine CXCL2ChromonesEnzyme InhibitorsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHMGB1 ProteinI-kappa B KinaseIndolesLipopolysaccharidesMacrophage ActivationMacrophagesMaleimidesMiceMorpholinesNeutrophil ActivationNeutrophilsPhosphorylationPulmonary EdemaTumor Necrosis Factor-alphaConceptsAMP-activated protein kinaseAMP-activated protein kinase activationInhibition of AMP-activated protein kinaseInactivating AMP-activated protein kinaseActivating AMP-activated protein kinaseInactivation of AMP-activated protein kinaseRegulate AMPK activityLPS-treated neutrophilsActivation of neutrophilsAMPK activationPI3K/Akt inhibitor LY294002Protein kinaseHistone 3Severity of LPS-induced lung injurySiRNA knockdownLPS-stimulated neutrophilsGSK3BIkBa degradationRegulating carbohydrateInhibitor LY294002LPS-induced activationLipid metabolismProduction of TNF-aLPS-induced inflammatory responseDephosphorylationSynapsis Alters RAG-Mediated Nicking at Tcrb Recombination Signal Sequences: Implications for the “Beyond 12/23” Rule
Banerjee JK, Schatz DG. Synapsis Alters RAG-Mediated Nicking at Tcrb Recombination Signal Sequences: Implications for the “Beyond 12/23” Rule. Molecular And Cellular Biology 2014, 34: 2566-2580. PMID: 24797073, PMCID: PMC4097660, DOI: 10.1128/mcb.00411-14.Peer-Reviewed Original ResearchAssessment of Phagocytic Activity of Cultured Macrophages Using Fluorescence Microscopy and Flow Cytometry
Sharma L, Wu W, Dholakiya SL, Gorasiya S, Wu J, Sitapara R, Patel V, Wang M, Zur M, Reddy S, Siegelaub N, Bamba K, Barile FA, Mantell LL. Assessment of Phagocytic Activity of Cultured Macrophages Using Fluorescence Microscopy and Flow Cytometry. Methods In Molecular Biology 2014, 1172: 137-145. PMID: 24908301, DOI: 10.1007/978-1-4939-0928-5_12.ChaptersMeSH KeywordsAnimalsCell LineFlow CytometryFluorescein-5-isothiocyanateFluorescent DyesGene ExpressionGranulocyte-Macrophage Colony-Stimulating FactorHMGB1 ProteinInterleukin-1betaMacrophagesMiceMicroscopy, FluorescenceMicrospheresPhagocytosisTransforming Growth Factor beta1Tumor Necrosis Factor-alphaConceptsCultured macrophagesHigh mobility group box 1Individual cellsInnate immune systemFluorescence microscopyNumerous diseasesPhagocytic processFluorescence microscopePhagocytic functionPhagocytic activityCell debrisPhagocytosisFlow cytometryMobility group box 1PhagocytesGroup box 1GM-CSFMacrophagesImmune systemTGF-β1Different cytokinesFlow cytometerIL-1βEngulfmentHomeostasisHuman Resistin Promotes Neutrophil Proinflammatory Activation and Neutrophil Extracellular Trap Formation and Increases Severity of Acute Lung Injury
Jiang S, Park D, Tadie J, Gregoire M, Deshane J, Pittet J, Abraham E, Zmijewski J. Human Resistin Promotes Neutrophil Proinflammatory Activation and Neutrophil Extracellular Trap Formation and Increases Severity of Acute Lung Injury. The Journal Of Immunology 2014, 192: 4795-4803. PMID: 24719460, PMCID: PMC4018664, DOI: 10.4049/jimmunol.1302764.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAMP-Activated Protein KinasesAnimalsChemokine CXCL2Disease Models, AnimalFemaleHistonesHMGB1 ProteinHumansLipopolysaccharidesLungMacrophages, PeritonealMaleMiceMice, KnockoutNeutrophil ActivationNeutrophilsResistinSeverity of Illness IndexToll-Like Receptor 4Tumor Necrosis Factor-alphaConceptsNeutrophil extracellular trap formationAcute lung injuryExtracellular trap formationSeverity of acute lung injuryActivation of AMP-activated protein kinaseLPS-induced acute lung injuryAMP-activated protein kinaseLung injuryRegulation of cellular bioenergeticsMouse resistinHuman resistinTrap formationTLR4-induced inflammatory responsesSeverity of LPS-induced acute lung injuryModel of type II diabetesProduction of proinflammatory cytokinesProtein kinaseProduction of TNF-aHistone 3Cellular bioenergeticsPattern of tissue distributionSevere pulmonary edemaInflammatory activity of neutrophilsModulate insulin resistanceIncreased neutrophil extracellular trap formation
2013
Cooperative recruitment of HMGB1 during V(D)J recombination through interactions with RAG1 and DNA
Little AJ, Corbett E, Ortega F, Schatz DG. Cooperative recruitment of HMGB1 during V(D)J recombination through interactions with RAG1 and DNA. Nucleic Acids Research 2013, 41: 3289-3301. PMID: 23325855, PMCID: PMC3597659, DOI: 10.1093/nar/gks1461.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesFluorescence anisotropy experimentsRAG-RSS complexesHigh mobility group box proteinAbsence of DNAGroup box proteinArchitectural proteinsPulldown experimentsRAG2 bindBox proteinSignal sequenceCooperative recruitmentComplex assemblyRecombinase complexStable integrationSequence specificitySynergistic binding effectAnisotropy experimentsAddition of DNAOrder of eventsRAG1DNAHMGB1 proteinProteinConcentration-dependent mannerHMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4
Tadie J, Bae H, Jiang S, Park D, Bell C, Yang H, Pittet J, Tracey K, Thannickal V, Abraham E, Zmijewski J. HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2013, 304: l342-l349. PMID: 23316068, PMCID: PMC3602738, DOI: 10.1152/ajplung.00151.2012.Peer-Reviewed Original ResearchConceptsHigh-mobility group box 1Neutrophil extracellular trapsNeutrophil extracellular trap formationHistone 3Neutralizing antibody to HMGB1Macrophage inflammatory protein-2Mice exposed to LPSProtein high-mobility group box 1DNA-associated proteinsMice treated with LPSAnti-HMGB1 antibodyFormation of neutrophil extracellular trapsToll-like receptor (TLR)4Toll-like receptor 4Bronchoalveolar lavage fluidLPS-exposed miceAmount of DNAInduce NET formationExposure of wild-typeExtracellular trap formationChromatin decondensationCytokines TNF-aIncubation of neutrophilsPulmonary neutrophilsAirway neutrophilsRAG and HMGB1 create a large bend in the 23RSS in the V(D)J recombination synaptic complexes
Ciubotaru M, Trexler AJ, Spiridon LN, Surleac MD, Rhoades E, Petrescu AJ, Schatz DG. RAG and HMGB1 create a large bend in the 23RSS in the V(D)J recombination synaptic complexes. Nucleic Acids Research 2013, 41: 2437-2454. PMID: 23293004, PMCID: PMC3575807, DOI: 10.1093/nar/gks1294.Peer-Reviewed Original Research
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