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 levelsInterventions to support fellowship application success among predoctoral physician-scientists
Fitzsimonds R, Gorelick F, Kazmierczak B. Interventions to support fellowship application success among predoctoral physician-scientists. JCI Insight 2024, 9: e175857. PMID: 38456505, PMCID: PMC10972582, DOI: 10.1172/jci.insight.175857.Peer-Reviewed Original Research
2023
Plasma 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
Renalase 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 levels
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 transportersSex Differences in the Exocrine Pancreas and Associated Diseases
Wang M, Gorelick F, Bhargava A. Sex Differences in the Exocrine Pancreas and Associated Diseases. Cellular And Molecular Gastroenterology And Hepatology 2021, 12: 427-441. PMID: 33895424, PMCID: PMC8255941, DOI: 10.1016/j.jcmgh.2021.04.005.Peer-Reviewed Original ResearchConceptsPancreatic diseaseSex differencesExocrine pancreasLevels of estrogenAcute pancreatitis modelOverall health outcomesSex-specific mechanismsNormal exocrine pancreasG protein-coupled receptorsSex-specific changesMajor sex differencesObstructive etiologyPremenopausal womenProtein-coupled receptorsPancreatic surgeryAdrenal glandPancreatic histopathologyPancreatic secretionProtective effectLow prevalenceGranule numberDiagnostic criteriaPancreatitis modelPancreatic anatomyAssociated disease
2020
Protein Lysine Acetylation An Unexpected Mediator in Pancreatitis
Gorelick FS. Protein Lysine Acetylation An Unexpected Mediator in Pancreatitis. Cellular And Molecular Gastroenterology And Hepatology 2020, 11: 883-884. PMID: 33279460, PMCID: PMC7900832, DOI: 10.1016/j.jcmgh.2020.11.010.Peer-Reviewed Original ResearchZinc: Roles in pancreatic physiology and disease
Wang M, Phadke M, Packard D, Yadav D, Gorelick F. Zinc: Roles in pancreatic physiology and disease. Pancreatology 2020, 20: 1413-1420. PMID: 32917512, PMCID: PMC7572834, DOI: 10.1016/j.pan.2020.08.016.Peer-Reviewed Original ResearchConceptsZinc deficiencyReduced zinc levelsPancreatic injuryChronic pancreatitisAcute pancreatitisIL-1βInflammatory cytokinesGastrointestinal diseasesPancreatic diseaseIntestinal absorptionAnimal modelsMacrophage activationCalcium homeostasisNutritional deficienciesBiologic effectsPancreatic physiologyZinc levelsCellular changesDiseasePreliminary dataPancreatitisInflammationEssential trace elementDeficiencyCytokinesAmerican Pancreatic Association Frank Brooks Symposium: Fifty Years of Pancreatic Cell Biology.
Williams JA, Groblewski GE, Gorelick FS, Mayerle J, Apte M, Gukovskaya AS. American Pancreatic Association Frank Brooks Symposium: Fifty Years of Pancreatic Cell Biology. Pancreas 2020, 49: 604-611. PMID: 32433396, PMCID: PMC7249997, DOI: 10.1097/mpa.0000000000001543.Peer-Reviewed Original ResearchTRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells
Gorelick F, Nathanson MH. TRPV4 helps Piezo1 put the squeeze on pancreatic acinar cells. Journal Of Clinical Investigation 2020, 130: 2199-2201. PMID: 32281947, PMCID: PMC7190901, DOI: 10.1172/jci136525.Peer-Reviewed Original ResearchConceptsPancreatic acinar cellsCalcium signalingAcinar cellsPlasma membrane calcium channelsGenetic deletion modelsMembrane calcium channelsCytosolic calcium levelsCell culture systemDeletion modelTransient receptor potential vanilloidPathogenesis of pancreatitisSignalingCulture systemCellsPathwayStimulation pathwayCalcium channels
2019
Precision Medicine in Pancreatic Disease-Knowledge Gaps and Research Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.
Lowe ME, Andersen DK, Caprioli RM, Choudhary J, Cruz-Monserrate Z, Dasyam AK, Forsmark CE, Gorelick FS, Gray JW, Haupt M, Kelly KA, Olive KP, Plevritis SK, Rappaport N, Roth HR, Steen H, Swamidass SJ, Tirkes T, Uc A, Veselkov K, Whitcomb DC, Habtezion A. Precision Medicine in Pancreatic Disease-Knowledge Gaps and Research Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Pancreas 2019, 48: 1250-1258. PMID: 31688587, PMCID: PMC7282491, DOI: 10.1097/mpa.0000000000001412.Peer-Reviewed Original ResearchConceptsPancreatic diseasePrecision medicineCurrent precision medicine approachesKidney Diseases workshopProspective clinical trialsNational InstitutePrecision medicine approachHealth care systemKidney diseaseRisk factorsClinical trialsFatal illnessMulticenter effortsMedicine approachDiseaseCare systemDisease mechanismsDiabetesPatient data setsMedicinePersonalized medicinePrecision imagingPatientsTherapyIllnessCELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation
Esteghamat F, Broughton JS, Smith E, Cardone R, Tyagi T, Guerra M, Szabó A, Ugwu N, Mani MV, Azari B, Kayingo G, Chung S, Fathzadeh M, Weiss E, Bender J, Mane S, Lifton RP, Adeniran A, Nathanson MH, Gorelick FS, Hwa J, Sahin-Tóth M, Belfort-DeAguiar R, Kibbey RG, Mani A. CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation. Nature Genetics 2019, 51: 1233-1243. PMID: 31358993, PMCID: PMC6675645, DOI: 10.1038/s41588-019-0470-3.Peer-Reviewed Original ResearchConceptsEarly-onset atherosclerosisMetabolic syndromeMetabolic syndrome traitsWhole-exome sequence analysisAttractive therapeutic targetPlatelet hyperactivationInsulin levelsPlasma insulinPlasma levelsInsulin sensitivityInsulin secretionTherapeutic targetPlatelet activationDisease mechanismsSyndrome traitsAtherosclerosisFunction mutationsSyndromeNovel lossInsulinMutationsSecretionAnimal Models: Challenges and Opportunities to Determine Optimal Experimental Models of Pancreatitis and Pancreatic Cancer.
Saloman JL, Albers KM, Cruz-Monserrate Z, Davis BM, Edderkaoui M, Eibl G, Epouhe AY, Gedeon JY, Gorelick FS, Grippo PJ, Groblewski GE, Husain SZ, Lai KKY, Pandol SJ, Uc A, Wen L, Whitcomb DC. Animal Models: Challenges and Opportunities to Determine Optimal Experimental Models of Pancreatitis and Pancreatic Cancer. Pancreas 2019, 48: 759-779. PMID: 31206467, PMCID: PMC6581211, DOI: 10.1097/mpa.0000000000001335.Peer-Reviewed Original ResearchRecent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders.
Gukovskaya AS, Gorelick FS, Groblewski GE, Mareninova OA, Lugea A, Antonucci L, Waldron RT, Habtezion A, Karin M, Pandol SJ, Gukovsky I. Recent Insights Into the Pathogenic Mechanism of Pancreatitis: Role of Acinar Cell Organelle Disorders. Pancreas 2019, 48: 459-470. PMID: 30973461, PMCID: PMC6461375, DOI: 10.1097/mpa.0000000000001298.Peer-Reviewed Original ResearchConceptsOrganelle dysfunctionCell death responseSecretion of proteinsAcinar cell homeostasisOrganelle disordersNascent proteinsDysfunctional organellesDeath responseAccessory proteinsVesicular compartmentsEndosomal pathwayCell homeostasisAcute pancreatitisEndoplasmic reticulumProtein synthesisCells triggersPancreatic acinar cellsLethal inflammatory diseaseDigestive enzymesCell constituentsRecent insightsDistinct mechanismsProteinOrganellesAcinar cell injury
2018
Cigarette toxin 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces experimental pancreatitis through α7 nicotinic acetylcholine receptors (nAChRs) in mice
Alahmari AA, Sreekumar B, Patel V, Ashat M, Alexandre M, Uduman AK, Akinbiyi EO, Ceplenski A, Shugrue CA, Kolodecik TR, Tashkandi N, Messenger SW, Groblewski GE, Gorelick FS, Thrower EC. Cigarette toxin 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces experimental pancreatitis through α7 nicotinic acetylcholine receptors (nAChRs) in mice. PLOS ONE 2018, 13: e0197362. PMID: 29870540, PMCID: PMC5988302, DOI: 10.1371/journal.pone.0197362.Peer-Reviewed Original ResearchConceptsNNK treatmentHuman acinar cellsNicotinic acetylcholine receptorsTrypsinogen activationAcetylcholine receptorsΑ7 nicotinic acetylcholine receptorIndependent risk factorMarkers of inflammationAcinar cellsΑ7nAChR knockout miceΑ7nAChR activationNeutrophil infiltrationWT miceAcute pancreatitisC57BL/6 miceCigarette smokingPancreatic edemaRisk factorsClinical studiesPancreatitisCigarette smokeKnockout miceExperimental pancreatitisΑ7 isoformPyknotic nuclei
2017
Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models
Biczo G, Vegh ET, Shalbueva N, Mareninova OA, Elperin J, Lotshaw E, Gretler S, Lugea A, Malla SR, Dawson D, Ruchala P, Whitelegge J, French SW, Wen L, Husain SZ, Gorelick FS, Hegyi P, Rakonczay Z, Gukovsky I, Gukovskaya AS. Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models. Gastroenterology 2017, 154: 689-703. PMID: 29074451, PMCID: PMC6369139, DOI: 10.1053/j.gastro.2017.10.012.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsArginineAutophagyBile Acids and SaltsCalcium SignalingCeruletideCholine DeficiencyCyclophilin DCyclophilinsDisease Models, AnimalEndoplasmic Reticulum StressEthionineGenetic Predisposition to DiseaseHumansLipid MetabolismMembrane Potential, MitochondrialMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial Proton-Translocating ATPasesPancreasPancreatitisPhenotypeRatsTime FactorsTrehaloseConceptsDevelopment of APAcute pancreatitisEndoplasmic reticulum stressLipid metabolismImpaired autophagyMitochondrial dysfunctionAnimal modelsL-arginine-induced pancreatitisTreatment of APCyclophilin D knockout micePathogenesis of APAdministration of trehalosePancreatic ER stressParameters of pancreatitisReticulum stressSevere acute pancreatitisPancreas of miceDifferent animal modelsER stressPrincipal downstream effectorPancreatic injuryPathologic responsePancreatitis tissuesCyclophilin DNormal pancreasThe 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 modelHuman Pancreatic Acinar Cells Proteomic Characterization, Physiologic Responses, and Organellar Disorders in ex Vivo Pancreatitis
Lugea A, Waldron RT, Mareninova OA, Shalbueva N, Deng N, Su HY, Thomas DD, Jones EK, Messenger SW, Yang J, Hu C, Gukovsky I, Liu Z, Groblewski GE, Gukovskaya AS, Gorelick FS, Pandol SJ. Human Pancreatic Acinar Cells Proteomic Characterization, Physiologic Responses, and Organellar Disorders in ex Vivo Pancreatitis. American Journal Of Pathology 2017, 187: 2726-2743. PMID: 28935577, PMCID: PMC5718097, DOI: 10.1016/j.ajpath.2017.08.017.Peer-Reviewed Original ResearchConceptsOrganellar morphologyEndoplasmic reticulum stressProteomic characterizationEndolysosomal functionProteomic analysisMolecular mechanismsMitochondrial depolarizationTaurolithocholic acidPhysiological functionsMuscarinic acetylcholine receptor M3Acute pancreatitis patientsBile acid taurolithocholic acidMacrophage inhibitory factorReticulum stressDigestive enzymesMuscarinic agonist carbacholTumor necrosis factorPhysiological responsesSimilar pathological responsesAcinar preparationsAcinar cell responsesCell viabilityInflammatory mediatorsSimilar mechanismPancreatitis patients