Featured Publications
MIF is a common genetic determinant of COVID-19 symptomatic infection and severity
Shin JJ, Fan W, Par-Young J, Piecychna M, Leng L, Israni-Winger K, Qing H, Gu J, Zhao H, Schulz WL, Unlu S, Kuster J, Young G, Liu J, Ko AI, Garcia A, Sauler M, Wisnewski AV, Young L, Orduña A, Wang A, Klementina O, Garcia AB, Hegyi P, Armstrong ME, Mitchell P, Ordiz DB, Garami A, Kang I, Bucala R. MIF is a common genetic determinant of COVID-19 symptomatic infection and severity. QJM 2022, 116: 205-212. PMID: 36222594, PMCID: PMC9620729, DOI: 10.1093/qjmed/hcac234.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorLow-expression MIF alleleCOVID-19 infectionMIF allelesCATT7 alleleHealthy controlsCOVID-19Serum macrophage migration inhibitory factorSymptomatic SARS-CoV-2 infectionHigher serum MIF levelsHigh-expression MIF allelesRetrospective case-control studySARS-CoV-2 infectionFunctional polymorphismsAvailable clinical characteristicsMultinational retrospective studySerum MIF levelsUninfected healthy controlsSymptomatic COVID-19Tertiary medical centerHealthy control subjectsCase-control studyMigration inhibitory factorCoronavirus disease 2019Common functional polymorphisms
2024
CD74 promotes the formation of an immunosuppressive tumor microenvironment in triple-negative breast cancer in mice by inducing the expansion of tolerogenic dendritic cells and regulatory B cells.
Pellegrino B, David K, Rabani S, Lampert B, Tran T, Doherty E, Piecychna M, Meza-Romero R, Leng L, Hershkovitz D, Vandenbark A, Bucala R, Becker-Herman S, Shachar I. CD74 promotes the formation of an immunosuppressive tumor microenvironment in triple-negative breast cancer in mice by inducing the expansion of tolerogenic dendritic cells and regulatory B cells. PLOS Biology 2024, 22: e3002905. PMID: 39576827, DOI: 10.1371/journal.pbio.3002905.Peer-Reviewed Original ResearchTriple-negative breast cancerMacrophage migration inhibitory factorImmunosuppressive tumor microenvironmentTolerogenic dendritic cellsRegulatory B cellsChronic lymphocytic leukemiaTumor microenvironmentDendritic cellsImmune cellsB cellsBreast cancerInfiltration of immune cellsAggressive breast cancer subtypeMassive infiltration of immune cellsLevels of CD74Cytokine macrophage migration inhibitory factorBreast cancer subtypesMigration inhibitory factorBinding to CD74Naive BTol-DCsLymphocytic leukemiaTumor environmentMassive infiltrationCancer subtypesAdvanced Glycosylation Endproducts
Bucala R, Vlassara H, Cerami A. Advanced Glycosylation Endproducts. 2024, 53-79. DOI: 10.1201/9781003574163-2.Peer-Reviewed Original ResearchMIF-CD74 Pathway and Its Effect on Effector T Cell Exhaustion in Alloimmunity
Younis N, Al Rahy N, Solhjou Z, Kurdi A, Zhang H, Al Chaar S, Djebli H, Badaoui A, Choi J, Piecychna M, Doherty E, Bucala R, Azzi J. MIF-CD74 Pathway and Its Effect on Effector T Cell Exhaustion in Alloimmunity. Journal Of The American Society Of Nephrology 2024, 35: 10.1681/asn.202461m1r2m1. DOI: 10.1681/asn.202461m1r2m1.Peer-Reviewed Original ResearchPrognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma
Valdez C, Sánchez-Zuno G, Osmani L, Ibrahim W, Galan A, Bacchiocchi A, Halaban R, Kulkarni R, Kang I, Bucala R, Tran T. Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma. Oncotarget 2024, 15: 507-520. PMID: 39028303, PMCID: PMC11259151, DOI: 10.18632/oncotarget.28615.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntigens, Differentiation, B-LymphocyteBiomarkers, TumorFemaleHistocompatibility Antigens Class IIHumansImmune Checkpoint InhibitorsIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMaleMelanomaMiddle AgedMutationPrognosisRetrospective StudiesSkin NeoplasmsConceptsMacrophage migration inhibitory factorImmune checkpoint inhibitionD-dopachrome tautomeraseExpression of macrophage migration inhibitory factorDrivers of tumor progressionInflammatory cell markersPatient tumor samplesPatient survival outcomesMigration inhibitory factorStatistically significant differenceCheckpoint inhibitionImmune therapyPrognostic valueSurvival outcomesResistant melanomaGene expressionImproved survivalRetrospective studyInflammatory markersTumor progressionCell markersTumor samplesClinical evidenceMelanomaBulk RNA sequencingDownregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia
Huang Y, Chen L, Li L, Qi Y, Tong H, Wu H, Xu J, Leng L, Cheema S, Sun G, Xia Z, McGuire J, Rodrigues B, Young L, Bucala R, Qi D. Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia. JCI Insight 2024, 9: e173240. PMID: 38973609, PMCID: PMC11383372, DOI: 10.1172/jci.insight.173240.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorDevelopment of hypertriglyceridemiaWhite adipose tissueAdipose LPLPAR2 expressionLevels of macrophage migration inhibitory factorElevated plasma TG levelsLPL expressionLipoprotein lipaseIncrease PAR2 expressionPlasma MIF levelsPlasma TG levelsMigration inhibitory factorPalmitic acid dietInhibited Akt phosphorylationMIF levelsLipoprotein lipase geneTG levelsObese humansPlasma TGHypertriglyceridemiaAkt phosphorylationLipid storageInhibitory factorAdipose tissuePOS1390 SINGLE-CELL PROFILING IDENTIFIES PERIPHERAL IMMUNE SIGNATURE OF CORONARY ARTERY DISEASE IN SLE PATIENTS
LI C, Osmani L, Gu J, Zhao H, Kang I, Bucala R, Dong X. POS1390 SINGLE-CELL PROFILING IDENTIFIES PERIPHERAL IMMUNE SIGNATURE OF CORONARY ARTERY DISEASE IN SLE PATIENTS. 2024, 929.2-929. DOI: 10.1136/annrheumdis-2024-eular.412.Peer-Reviewed Original ResearchA small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus
Li J, Leng L, Pantouris G, Manjula R, Piecychna M, Abriola L, Hu B, Lolis E, Armstrong M, Donnelly S, Bucala R. A small-molecule allele-selective transcriptional inhibitor of the MIF immune susceptibility locus. Journal Of Biological Chemistry 2024, 300: 107443. PMID: 38838773, PMCID: PMC11259703, DOI: 10.1016/j.jbc.2024.107443.Peer-Reviewed Original ResearchPromoter microsatellitesGene expressionMicrosatellite repeat numberMacrophage migration inhibitory factorLength-dependent mannerRNA expression analysisSusceptibility lociFunctional variantsSmall molecule inhibitorsExpression analysisPharmacogenomic developmentRepeat numberMicrosatelliteFunctional interactionsTranscription inhibitorInflammatory gene expressionMIF mRNA expressionCytokine macrophage migration inhibitory factorTranscriptionGenesProtein expressionMigration inhibitory factorExpressionInhibitory factorExpressing macrophagesMacrophage-derived macrophage migration inhibitory factor mediates renal injury in anti-glomerular basement membrane glomerulonephritis
Yang H, Li J, Huang X, Bucala R, Xu A, Lan H. Macrophage-derived macrophage migration inhibitory factor mediates renal injury in anti-glomerular basement membrane glomerulonephritis. Frontiers In Immunology 2024, 15: 1361343. PMID: 38846956, PMCID: PMC11153660, DOI: 10.3389/fimmu.2024.1361343.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorMigration inhibitory factorTreatment of immune-mediated kidney diseasesMacrophage MIFMIF depletionPathogenic roleSource of MIFImmune-mediated kidney diseasesAnti-glomerular basement membrane glomerulonephritisInhibitory factorT cell recruitmentGlomerular crescent formationTh17 immune responsesReduced serum creatininePolarization of macrophagesRenal macrophagesSerum creatinineCrescentic glomerulonephritisInhibiting Th1Renal injuryControl miceCreatine clearanceCrescent formationMembranous glomerulonephritisConditional ablationAlveolar Type 2 Cells With Impaired Proteostasis Signal to Monocyte-derived Macrophages Via a MIF/DDT-CD74 Signaling Network to Promotes Pulmonary Fibrosis in IPF
Kim S, Nouws J, Cooley J, Ahangari F, Leng L, Elias J, Kaminski N, Lee P, Redente E, Kang M, Sun H, Herzog E, Bucala R, Prasse A, Sauler M. Alveolar Type 2 Cells With Impaired Proteostasis Signal to Monocyte-derived Macrophages Via a MIF/DDT-CD74 Signaling Network to Promotes Pulmonary Fibrosis in IPF. 2024, a3001-a3001. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a3001.Peer-Reviewed Original ResearchMacrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities
Valdez C, Sánchez-Zuno G, Bucala R, Tran T. Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities. International Journal Of Molecular Sciences 2024, 25: 4849. PMID: 38732068, PMCID: PMC11084905, DOI: 10.3390/ijms25094849.Peer-Reviewed Original ResearchConceptsInhibition of MIFResponse to infectionNon-canonical signaling pathwaysClinical studiesCancer patientsClinical trialsInflammatory cytokinesDriving tumorigenesisClinical explorationCancer typesCancerDual inhibitionTherapeutic targetIn vivoIn vitroSignaling pathwayMIFAntitumor candidateBinding partnersMIF-Modulated Spinal Proteins Associated with Persistent Bladder Pain: A Proteomics Study
Ye S, Agalave N, Ma F, Mahmood D, Al-Grety A, Khoonsari P, Leng L, Svensson C, Bucala R, Kultima K, Vera P. MIF-Modulated Spinal Proteins Associated with Persistent Bladder Pain: A Proteomics Study. International Journal Of Molecular Sciences 2024, 25: 4484. PMID: 38674069, PMCID: PMC11050327, DOI: 10.3390/ijms25084484.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, B-LymphocyteCystitis, InterstitialDisease Models, AnimalFemaleHistocompatibility Antigens Class IIHyperalgesiaIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMiceProteomicsReceptors, CXCR4Receptors, ImmunologicSpinal CordUrinary BladderConceptsMacrophage migration inhibitory factorProtease activated receptor 4C-X-C chemokine receptor type 4Bladder hyperalgesiaBladder painSpinal proteinsMIF receptor CD74MIF antagonismL6-S1 spinal segmentsSpinal mechanismsInterstitial cystitis/bladder pain syndromeMIF receptorSeparate groups of miceChemokine receptor type 4Associated with reliefGroups of miceC-X-CMigration inhibitory factorChanges compared to controlsBladder inflammationPain syndromeFemale miceNo significant changesSham i.Receptor 4IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination
Park H, Shin M, Shin J, Kim H, Kang B, Par-Young J, Unlu S, Afinogenova Y, Catanzaro J, Young J, Kim M, Lee S, Jeon S, You S, Racke M, Bucala R, Kang I. IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination. EBioMedicine 2024, 103: 105114. PMID: 38640835, PMCID: PMC11041015, DOI: 10.1016/j.ebiom.2024.105114.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsCOVID-19 mRNA vaccinesAntigen-specific CD4<sup>+</sup> T cell responsesT cell responsesPrimary antibody deficiencyCD4<sup>+</sup> T cell responsesT cellsIL-1R1MRNA vaccinesIL-1IgG antibodiesAntigen-specific CD4<sup>+</sup> T cellsCD4+ T cell responsesLevels of IL-1R1Human CD4<sup>+</sup> T cellsIL-1 receptor 1Healthy individualsDose of COVID-19 mRNA vaccineAntigen-specific CD4IL-1R1 expressionT cell immunityRepetitive antigenic stimulationCytokines interleukin (IL)-1Immune response to virusesExpression of IL-1R1“Rounding Third Base and Heading Home”: Arthritis & Rheumatology in 2024
Solomon D, Kaplan M, Nigrovic P, Bucala R. “Rounding Third Base and Heading Home”: Arthritis & Rheumatology in 2024. Arthritis & Rheumatology 2024, 76: 819-822. PMID: 38572586, DOI: 10.1002/art.42828.Peer-Reviewed Original ResearchA small molecule macrophage migration inhibitory factor agonist ameliorates age-related myocardial intolerance to ischemia-reperfusion insults via metabolic regulation
Wang H, Slotabec L, Didik S, Li Z, Leng L, Zhao B, Bucala R, Li J. A small molecule macrophage migration inhibitory factor agonist ameliorates age-related myocardial intolerance to ischemia-reperfusion insults via metabolic regulation. Metabolism 2024, 153: 155792. PMID: 38232801, PMCID: PMC10932879, DOI: 10.1016/j.metabol.2024.155792.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorActivating AMP-activated protein kinaseI/R stressAging heartMacrophage migration inhibitory factor expressionCardiac metabolic profileReactive oxygen speciesIschemia-reperfusion insultIschemia-reperfusion (I/RAMP-activated protein kinaseMIF signalingMigration inhibitory factorDecreased myocardial infarct sizeAccumulation of reactive oxygen speciesMyocardial infarct sizeSystolic functionInnate cytokinesPharmacological augmentationSenescent heartsAged myocardiumSenescent myocardiumAge-related reductionIschemia-reperfusionI/R injuryMetabolic profileMIF contribution to progressive brain diseases
Matejuk A, Benedek G, Bucala R, Matejuk S, Offner H, Vandenbark A. MIF contribution to progressive brain diseases. Journal Of Neuroinflammation 2024, 21: 8. PMID: 38178143, PMCID: PMC10765708, DOI: 10.1186/s12974-023-02993-6.Peer-Reviewed Original ResearchConceptsBrain diseasesMultiple sclerosisAlzheimer's diseaseMacrophage migration inhibitory factorModulation of neuroinflammationNumerous neurologic diseasesMigration inhibitory factorProgressive brain diseaseNew therapeutic strategiesInflammatory mediatorsChronic inflammationAutoimmune diseasesVascular diseaseNervous system developmentNeurologic diseaseNeuroendocrine functionPsychiatric disordersTherapeutic strategiesEconomic burdenNeurological diseasesNew biomarkersInhibitory factorNeurodegenerative pathologiesDiseaseNovel therapeuticsThe Emerging Spectrum of Somatic Mutation in Rheumatic Disease: Clonal Hematopoiesis Connects Aging With Giant Cell Arteritis
Bucala R, Tsao B. The Emerging Spectrum of Somatic Mutation in Rheumatic Disease: Clonal Hematopoiesis Connects Aging With Giant Cell Arteritis. Arthritis & Rheumatology 2024, 76: 351-353. PMID: 37961826, PMCID: PMC11253228, DOI: 10.1002/art.42745.Peer-Reviewed Original ResearchMacrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review
Jarmula J, Lee J, Lauko A, Rajappa P, Grabowski M, Dhawan A, Chen P, Bucala R, Vogelbaum M, Lathia J. Macrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review. Neuro-Oncology Advances 2024, 6: vdae142. PMID: 39233830, PMCID: PMC11372298, DOI: 10.1093/noajnl/vdae142.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorPrimary CNS tumorsCentral nervous systemMigration inhibitory factorCNS tumorsPrimary central nervous systemInhibitory factorTherapeutic targetPre-clinical studiesFunctions of macrophage migration inhibitory factorPreclinical modelsImmune evasionSmall molecule inhibitorsNeuro-oncologyClinical trialsTumor initiationClinical translationMonoclonal antibodiesTumorigenic processNervous systemTherapeutic requirementsCell proliferationTherapeutic developmentTumorEffective targetPotential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus
Fan W, Wei B, Chen X, Zhang Y, Xiao P, Li K, Zhang Y, Huang J, Leng L, Bucala R. Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus. Arthritis Research & Therapy 2024, 26: 31. PMID: 38243295, PMCID: PMC10799493, DOI: 10.1186/s13075-024-03263-3.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsRhoA GTPaseExpression levelsTreatment of SLEFunctions of RhoA.Knockdown of RhoAI IFN-stimulated genesSiRNA-mediated knockdownI interferonEnzyme-linked immunoassayIFN-stimulated genesGTPase signalingExpression levels of RhoASLE patientsLevels of RhoALupus erythematosusSLE peripheral blood mononuclear cellsGTPase regulatorHealthy controlsExpression of RhoAResponse pathwaysReporter gene assayRhoAType I IFN signalingSignal transducer
2023
Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease
Young J, Park H, Kim M, Par-Young J, Bartlett H, Kim H, Unlu S, Osmani L, Shin M, Bucala R, van Dyck C, Allore H, Mecca A, You S, Kang I. Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease. Immunity & Ageing 2023, 20: 71. PMID: 38042785, PMCID: PMC10693128, DOI: 10.1186/s12979-023-00396-y.Peer-Reviewed Original ResearchPeripheral bloodT cellsAlzheimer's diseaseEM CD8Memory CD8Gene signatureAge-related immune changesIL-7 receptor alphaEffector memory CD8Strong risk factorT cell expansionAD genesAge-associated expansionImmune changesRisk factorsCD8Dementia patientsIL-7RNeuropsychological testingReceptor alphaNeurocognitive functionRT-qPCR resultsDisease severityPatientsNormal persons