2024
Chemical complementarity of tumor resident, T-cell receptor CDR3s and renalase-1 correlates with increased melanoma survival
Zaman S, Gorelick F, Chrobrutskiy A, Chobrutskiy B, Desir G, Blanck G. Chemical complementarity of tumor resident, T-cell receptor CDR3s and renalase-1 correlates with increased melanoma survival. Oncotarget 2024, 15: 550-561. PMID: 39102218, PMCID: PMC11299663, DOI: 10.18632/oncotarget.28633.Peer-Reviewed Original ResearchConceptsT cell receptorOverall survivalT cellsAssociated with improved overall survivalT-cell receptor CDR3sPromote T cell activationImproved overall survivalSurvival of melanomaPancreatic cancer patientsT cell activationT cell receptor recognitionTumor-residentTumor rejectionMelanoma patientsMelanoma growthMelanoma survivalImmune signature genesSurvival associationsCancer patientsMelanomaSignature genesAmino acid sequenceSurvivalPatientsExpression levels
2023
An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model
Charkoftaki G, Aalizadeh R, Santos-Neto A, Tan W, Davidson E, Nikolopoulou V, Wang Y, Thompson B, Furnary T, Chen Y, Wunder E, Coppi A, Schulz W, Iwasaki A, Pierce R, Cruz C, Desir G, Kaminski N, Farhadian S, Veselkov K, Datta R, Campbell M, Thomaidis N, Ko A, Thompson D, Vasiliou V. An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model. Human Genomics 2023, 17: 80. PMID: 37641126, PMCID: PMC10463861, DOI: 10.1186/s40246-023-00521-4.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsDisease severityViral outbreaksFuture viral outbreaksLength of hospitalizationIntensive care unitWorse disease prognosisLife-threatening illnessEffective medical interventionsCOVID-19Clinical decision treeGlucuronic acid metabolitesNew potential biomarkersHospitalization lengthCare unitComorbidity dataSerotonin levelsDisease progressionHealthy controlsPatient outcomesDisease prognosisPatient transferPatientsHealthcare resourcesPotential biomarkersDifferences in Mortality Among Patients With Asthma and COPD Hospitalized With COVID-19
Liu Y, Rajeevan H, Simonov M, Lee S, Wilson F, Desir G, Vinetz J, Yan X, Wang Z, Clark B, Possick J, Price C, Lutchmansingh D, Ortega H, Zaeh S, Gomez J, Cohn L, Gautam S, Chupp G. Differences in Mortality Among Patients With Asthma and COPD Hospitalized With COVID-19. The Journal Of Allergy And Clinical Immunology In Practice 2023, 11: 3383-3390.e3. PMID: 37454926, PMCID: PMC10787810, DOI: 10.1016/j.jaip.2023.07.006.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseType 2 inflammationCOVID-19 severitySOFA scoreAirway diseaseNoneosinophilic asthmaSequential Organ Failure Assessment scoreOrgan Failure Assessment scoreSevere coronavirus disease 2019Higher SOFA scoreMedian SOFA scoreRetrospective cohort studyObstructive pulmonary diseaseOdds of mortalityLower SOFA scoresCells/μLCOVID-19 outcomesCoronavirus disease 2019Logistic regression analysisCOVID-19Clinical confoundersAsthma patientsCohort studyImmunological factorsClinical featuresPlasma renalase levels are associated with the development of acute pancreatitis
Wang M, Weiss F, Guo X, Kolodecik T, Bewersdorf J, Laine L, Lerch M, Desir G, Gorelick F. Plasma renalase levels are associated with the development of acute pancreatitis. Pancreatology 2023, 23: 158-162. PMID: 36697349, DOI: 10.1016/j.pan.2023.01.001.Peer-Reviewed Original ResearchConceptsAcute pancreatitisSevere diseasePlasma renalase levelsAcute pancreatitis patientsSevere acute pancreatitisAcute pancreatitis modelPlasma renalaseRenalase levelsSignificant morbidityPancreatitis patientsPlasma levelsHealthy controlsPancreatitis modelPancreatitisPatientsPlasma samplesRenalaseDiseaseNonparametric statistical analysisSecretory proteinsMorbidityStatistical analysisMortalityLevels
2022
Vaccination With Leptospira interrogans PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice From Severe Leptospirosis and Reduces Bacterial Load in the Liver and Kidney
Chaurasia R, Salovey A, Guo X, Desir G, Vinetz JM. Vaccination With Leptospira interrogans PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice From Severe Leptospirosis and Reduces Bacterial Load in the Liver and Kidney. Frontiers In Cellular And Infection Microbiology 2022, 12: 926994. PMID: 35837473, PMCID: PMC9274288, DOI: 10.3389/fcimb.2022.926994.Peer-Reviewed Original ResearchConceptsLethal challenge infectionChallenge infectionBacterial loadC3H/HeJ miceKey target organClinical pathogenesisSevere leptospirosisOrgan infectionProtein immunizationHeJ miceSerovar CanicolaTarget organsAnimal modelsLeptospirosis pathogenesisCellular pathogenesisMicePathogenesisInfectionLeptospira interrogansVirulence factorsModifying proteinsImmunizationKidneyLeptospirosisLiverAssociations of Long-Term Visit-to-Visit Blood Pressure Variability With Subclinical Kidney Damage and Albuminuria in Adulthood: a 30-Year Prospective Cohort Study
Wang Y, Zhao P, Chu C, Du MF, Zhang XY, Zou T, Hu GL, Zhou HW, Jia H, Liao YY, Chen C, Ma Q, Wang D, Yan Y, Sun Y, Wang KK, Niu ZJ, Zhang X, Man ZY, Wu YX, Wang L, Li HX, Zhang J, Li CH, Gao WH, Gao K, Lu WH, Desir GV, Delles C, Chen FY, Mu JJ. Associations of Long-Term Visit-to-Visit Blood Pressure Variability With Subclinical Kidney Damage and Albuminuria in Adulthood: a 30-Year Prospective Cohort Study. Hypertension 2022, 79: 1247-1256. PMID: 35360932, PMCID: PMC9093226, DOI: 10.1161/hypertensionaha.121.18658.Peer-Reviewed Original ResearchConceptsLong-term blood pressure variabilitySubclinical kidney damageAverage real variabilityBlood pressure variabilityLong-term visitCreatinine ratioUrinary albuminMean BPKidney damageCardiovascular diseasePressure variabilityHigh riskCumulative exposureHanzhong Adolescent Hypertension StudyVisit blood pressure variabilityProspective cohort studyGlomerular filtration rateRisk of albuminuriaClinical characteristicsCohort studyOngoing cohortKidney diseaseHypertension StudyFiltration rateAlbuminuriaRenalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation
Wang M, Silva T, Toothaker JM, McCourt BT, Shugrue C, Desir G, Gorelick F, Konnikova L. Renalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation. Scientific Reports 2022, 12: 4953. PMID: 35322081, PMCID: PMC8943056, DOI: 10.1038/s41598-022-08817-6.Peer-Reviewed Original ResearchConceptsPlacental tissuePlacental villiHofbauer cellsPlacental developmentEndogenous productionAnti-inflammatory milieuPotential roleHuman placental tissueFull-term placentaPlacental factorsFetal interfaceDecidual samplesPlacental functionChorionic plateImmunoreactive cellsPlacental samplesHuman gestationRenalaseBulk RNA sequencingHuman placentaPlacentaQuantification of immunohistochemistryProtein levelsTrophoblastTransmission of nutrientsAssociation of renalase with clinical outcomes in hospitalized patients with COVID-19
Safdar B, Wang M, Guo X, Cha C, Chun HJ, Deng Y, Dziura J, El-Khoury JM, Gorelick F, Ko AI, Lee AI, Safirstein R, Simonov M, Zhou B, Desir GV. Association of renalase with clinical outcomes in hospitalized patients with COVID-19. PLOS ONE 2022, 17: e0264178. PMID: 35259186, PMCID: PMC8903289, DOI: 10.1371/journal.pone.0264178.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsRenalase levelsIntensive care unit admissionHospitalized COVID-19 patientsMean age 64 yearsCOVID-19Cox proportional hazards modelCare unit admissionPrimary composite outcomeRetrospective cohort studyUse of vasopressorsSevere COVID-19IL-6 levelsAge 64 yearsRisk of deathCOVID-19 subjectsInitial disease severityProportional hazards modelCOVID-19 diseasePlasma renalaseUnit admissionICU admissionCohort studyComposite outcomeCytokine levelsInhibition of renalase drives tumour rejection by promoting T cell activation
Guo X, Jessel S, Qu R, Kluger Y, Chen TM, Hollander L, Safirstein R, Nelson B, Cha C, Bosenberg M, Jilaveanu LB, Rimm D, Rothlin CV, Kluger HM, Desir GV. Inhibition of renalase drives tumour rejection by promoting T cell activation. European Journal Of Cancer 2022, 165: 81-96. PMID: 35219026, PMCID: PMC8940682, DOI: 10.1016/j.ejca.2022.01.002.Peer-Reviewed Original ResearchConceptsPD-1 inhibitorsMurine melanoma modelMelanoma-bearing miceMelanoma modelTumor microenvironmentTumor rejectionCell death protein 1 (PD-1) inhibitorsAnti-PD-1 activityEnhanced T cell infiltrationT cell-dependent fashionMelanoma cellsMelanoma tumor regressionPreclinical melanoma modelsT cell infiltrationNatural killer cellsForkhead box P3Expression of IFNγWild-type miceProtein 1 inhibitorT cell activationTumor cell contentWild-type melanoma cellsCD4 cellsAdvanced melanomaAntibody treatmentKidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation
Guo X, Xu L, Velazquez H, Chen TM, Williams RM, Heller DA, Burtness B, Safirstein R, Desir GV. Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation. Journal Of The American Society Of Nephrology 2022, 33: 342-356. PMID: 34921111, PMCID: PMC8819981, DOI: 10.1681/asn.2021040439.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntineoplastic AgentsCell LineCisplatinCreatinineDisease Models, AnimalGene ExpressionGlomerular Filtration RateHepatitis A Virus Cellular Receptor 1HumansKidneyMiceMice, Inbred C57BLMice, KnockoutMonoamine OxidaseNanocapsulesPeptidesRenal Insufficiency, ChronicConceptsRenal proximal tubulesSingle-cell RNA sequencing analysisMesoscale nanoparticlesFirst doseCisplatin chemotherapyProximal tubulesAgonist peptideInduced Chronic Kidney DiseaseGenetic deletionNeck squamous cell carcinomaRNA sequencing analysisCisplatin-induced AKIKidney-targeted deliveryChronic kidney diseaseDevelopment of CKDSquamous cell carcinomaAdministration of cisplatinPlasma renalaseAdvanced headCell carcinomaInflammatory cytokinesKidney diseasePlasma creatinineSystemic administrationRegulated necrosisRENALASE: DISCOVERY, BIOLOGY, AND THERAPEUTIC APPLICATIONS.
Desir GV. RENALASE: DISCOVERY, BIOLOGY, AND THERAPEUTIC APPLICATIONS. Transactions Of The American Clinical And Climatological Association 2022, 132: 117-125. PMID: 36196172, PMCID: PMC9480547.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseStage renal diseaseCardiovascular complicationsOrgan survivalRenal diseaseAcute injuryKidney diseaseChronic injurySignificant burdenRenalaseStressful stimuliPeptide agonistsNicotinamide adenine dinucleotideMitochondrial functionInjuryEnergy metabolismDiseaseTherapeutic applicationsAdenine dinucleotideCellsComplicationsPathophysiologyAgonistsKidneyPancreas
2021
Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma
Gao Y, Wang M, Guo X, Hu J, Chen TM, Finn S, Lacy J, Kunstman JW, H. C, Bellin MD, Robert ME, Desir GV, Gorelick FS. Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma. PLOS ONE 2021, 16: e0250539. PMID: 34587190, PMCID: PMC8480607, DOI: 10.1371/journal.pone.0250539.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Pancreatic DuctalCase-Control StudiesFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedMonoamine OxidaseNeoplasm GradingPancreatic NeoplasmsPrognosisProspective StudiesRetrospective StudiesSurvival AnalysisUp-RegulationYoung AdultConceptsPlasma renalase levelsBorderline resectable PDACRenalase levelsPDAC precursor lesionsOverall survivalPDAC tissuesTumor characteristicsResectable PDACChronic pancreatitisPrecursor lesionsNormal pancreasPancreatic ductal adenocarcinoma growthAdvanced tumor characteristicsVaried clinical stagesWorse tumor characteristicsNode-positive diseasePancreatic ductal adenocarcinomaNormal pancreatic headSpindle-shaped cellsPlasma renalaseRenalase expressionUnderwent resectionAbdominal traumaPancreatic headPositive diseaseRenalase: A Multi-Functional Signaling Molecule with Roles in Gastrointestinal Disease
Pointer TC, Gorelick FS, Desir GV. Renalase: A Multi-Functional Signaling Molecule with Roles in Gastrointestinal Disease. Cells 2021, 10: 2006. PMID: 34440775, PMCID: PMC8391834, DOI: 10.3390/cells10082006.Peer-Reviewed Original ResearchConceptsProsurvival effectAcute cerulein pancreatitisRole of renalaseAnti-inflammatory effectsDisease modelsAcute organ injuryRelevant clinical settingsShortens life expectancyPreclinical disease modelsCell survivalHuman cancer tissuesCancer cell survivalOrgan injuryAcute injuryPancreatic cancerIntestinal diseaseGastrointestinal diseasesRodent modelsCerulein pancreatitisSelect cancersCancer tissuesRenalaseClinical settingTherapeutic agentsExport transportersChallenges in interpreting cytokine data in COVID-19 affect patient care and management
Wang SY, Takahashi T, Pine AB, Damsky WE, Simonov M, Zhang Y, Kieras E, Price CC, King BA, Siegel MD, Desir GV, Lee AI, Iwasaki A, Chun HJ. Challenges in interpreting cytokine data in COVID-19 affect patient care and management. PLOS Biology 2021, 19: e3001373. PMID: 34358229, PMCID: PMC8372945, DOI: 10.1371/journal.pbio.3001373.Peer-Reviewed Original Research
2019
Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease
Landau SI, Guo X, Velazquez H, Torres R, Olson E, Garcia-Milian R, Moeckel GW, Desir GV, Safirstein R. Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease. Kidney International 2019, 95: 797-814. PMID: 30904067, PMCID: PMC6543531, DOI: 10.1016/j.kint.2018.11.042.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseKidney diseaseKidney injuryCisplatin-induced chronic kidney diseaseCisplatin-induced acute kidney injuryToll-like receptor 2Regulated necrosis pathwaysReversible kidney injuryAcute kidney injuryChronic kidney injuryProximal tubular damageKidney injury markersDoses of cisplatinEvidence of fibrosisMechanisms of progressionEffective chemotherapeutic agentWestern blot analysisFirst doseInjury markersIntraperitoneal cisplatinSignificant nephrotoxicityTubular damageKidney functionSecond doseCisplatin administrationElevated renalase levels in patients with acute coronary microvascular dysfunction – A possible biomarker for ischemia
Safdar B, Guo X, Johnson C, D'Onofrio G, Dziura J, Sinusas AJ, Testani J, Rao V, Desir G. Elevated renalase levels in patients with acute coronary microvascular dysfunction – A possible biomarker for ischemia. International Journal Of Cardiology 2019, 279: 155-161. PMID: 30630613, PMCID: PMC6482834, DOI: 10.1016/j.ijcard.2018.12.061.Peer-Reviewed Original ResearchConceptsCoronary microvascular dysfunctionFramingham risk scorePET/CTChest painInflammatory markersMicrovascular dysfunctionEmergency departmentRisk scoreRb-82 PET/CTElevated renalase levelsAcute chest painCoronary artery diseaseC-reactive proteinVascular endothelial growth factorAnti-inflammatory proteinTumor necrosis factorEndothelial growth factorAngina historyCMD diagnosisRenalase levelsHypertensive crisisED presentationsHemodynamic instabilityArtery diseaseHeart failure
2017
The serum protein renalase reduces injury in experimental pancreatitis
Kolodecik TR, Reed AM, Date K, Shugrue C, Patel V, Chung SL, Desir GV, Gorelick FS. The serum protein renalase reduces injury in experimental pancreatitis. Journal Of Biological Chemistry 2017, 292: 21047-21059. PMID: 29042438, PMCID: PMC5743078, DOI: 10.1074/jbc.m117.789776.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsAnimalsAnti-Inflammatory Agents, Non-SteroidalBiomarkersCalcium SignalingCarbacholCell LineCeruletideEnzyme ActivationFluorescent Antibody Technique, IndirectGene Expression Regulation, EnzymologicHumansHypertensionLigandsMembrane Transport ModulatorsMiceMice, KnockoutMonoamine OxidasePancreasPancreatitisPlasma Membrane Calcium-Transporting ATPasesRecombinant Fusion ProteinsTaurolithocholic AcidConceptsRecombinant human renalaseAcute pancreatitisAcute injuryCell injuryAcinar cell injuryHuman acinar cellsCytosolic calcium levelsPlasma membrane calcium ATPasePancreatitis onsetIschemic injuryWT micePathological increaseHistological changesProtective effectSevere diseaseMurine modelMembrane calcium ATPasePancreatitisCalcium levelsExperimental pancreatitisBile acidsTissue damageRenalaseInjuryCerulein modelExtracellular renalase protects cells and organs by outside‐in signalling
Wang Y, Safirstein R, Velazquez H, Guo X, Hollander L, Chang J, Chen T, Mu J, Desir GV. Extracellular renalase protects cells and organs by outside‐in signalling. Journal Of Cellular And Molecular Medicine 2017, 21: 1260-1265. PMID: 28238213, PMCID: PMC5487909, DOI: 10.1111/jcmm.13062.Peer-Reviewed Original ResearchConceptsProtective effectNovel therapeutic strategiesCancer cell growthBlood pressureOrgan injuryJAK/STATHeart rateTherapeutic strategiesToxic injuryCytoprotective actionMitogen-activated protein kinase pathwayRenalaseTranslational opportunitiesTumor cellsCellular actionsProtein kinase BInitial reportProtein kinase pathwayInjuryKinase BOrgansKinase pathwayGrowth-related genesCell growthExtracellular renalase
2016
Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism
Hollander L, Guo X, Velazquez H, Chang J, Safirstein R, Kluger H, Cha C, Desir G. Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism. Cancer Research 2016, 76: 3884-3894. PMID: 27197188, PMCID: PMC5031238, DOI: 10.1158/0008-5472.can-15-1524.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBiomarkers, TumorBlotting, WesternCase-Control StudiesCell CycleCell ProliferationFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunoenzyme TechniquesMacrophagesMaleMelanomaMiceMice, Inbred C57BLMice, NudeMonoamine OxidaseNeoplasm StagingP38 Mitogen-Activated Protein KinasesPrognosisProto-Oncogene Proteins c-aktSignal TransductionSTAT3 Transcription FactorSurvival RateTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsTumor-associated macrophagesDisease-specific survivalManagement of melanomaPotential therapeutic implicationsCell cycle inhibitor p21Melanoma cell growthPI3K/AktMelanoma cell survivalCell growth arrestPathogenic rolePrimary melanomaToxic injuryMurine xenograftsTherapeutic implicationsTumor growthClinical specimensRenalaseBax activationTumor microenvironmentTumor cellsInhibitor p21Growth arrestSurvival factorElevated expressionMAPK pathwayA Remote Role for Renalase
Giordano FJ, Wang Y, Desir GV. A Remote Role for Renalase. EBioMedicine 2016, 9: 27-28. PMID: 27374133, PMCID: PMC4972559, DOI: 10.1016/j.ebiom.2016.06.034.Peer-Reviewed Original Research