2024
Charting the metabolic biogeography of the colorectum in cancer: challenging the right sided versus left sided classification
Jain A, Morris M, Berardi D, Arora T, Domingo-Almenara X, Paty P, Rattray N, Kerekes D, Lu L, Khan S, Johnson C. Charting the metabolic biogeography of the colorectum in cancer: challenging the right sided versus left sided classification. Molecular Cancer 2024, 23: 211. PMID: 39342363, PMCID: PMC11438248, DOI: 10.1186/s12943-024-02133-5.Peer-Reviewed Original ResearchConceptsRectal cancerNormal mucosaMetabolite abundancePatient-matched tumorTumor-specific metabolitesMetabolic heterogeneityPatient survivalRectosigmoid colonSigmoid colonAnatomic subsitePatient-matched normal mucosaTransverse colonMetabolomic profilesAscending colonCRC biomarkersMetabolome DatabaseDescending colonMetabolite changesLeft-sidedRight-sidedColorectumRisk factorsMetabolome mapCancerTumorGrowth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex
Aladelokun O, Lu L, Zheng J, Yan H, Jain A, Gibson J, Khan S, Johnson C. Growth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex. Human Genomics 2024, 18: 67. PMID: 38886847, PMCID: PMC11184737, DOI: 10.1186/s40246-024-00635-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAspartate-Ammonia LigaseCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorCell ProliferationColorectal NeoplasmsFemaleGene Expression Regulation, NeoplasticHCT116 CellsHeterograftsHumansMaleMiceReceptors, EstrogenReceptors, G-Protein-CoupledSex FactorsXenograft Model Antitumor AssaysConceptsFemale tumor-bearing miceFemale CRC patientsTumor-bearing miceCRC patientsTumor growthInferior survivalAssociated with inferior survivalMetabolic reprogrammingG protein-coupled estrogen receptorTriggering metabolic reprogrammingSustained tumor growthSuppressed tumor growthExpression of asparagine synthetaseCancer cell linesBackgroundSex-related differencesSurvival improvementImpact of sexFemale miceEstrogen receptorCancer growthTranslational relevanceRewiring of metabolic pathwaysCancer burdenMetabolic pathwaysAsparagine synthetase
2023
Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study
Vollmar A, Rattray N, Cai Y, Jain A, Yan H, Deziel N, Calafat A, Wilcox A, Jukic A, Johnson C. Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study. Environmental Health Perspectives 2023, 131: 097006. PMID: 37702489, PMCID: PMC10498870, DOI: 10.1289/ehp12125.Peer-Reviewed Original ResearchConceptsUrinary paraben concentrationsDiet-related metabolitesEarly Pregnancy StudyUrinary metabolomePregnancy StudyParaben concentrationsReproductive functionMultivariable linear regressionFemale reproductive functionDietary exposure assessmentUltrahigh-performance liquid chromatography-quadrupole timeMetabolomic analysisParaben exposureProspective cohortLiquid chromatography-quadrupole timeOrthogonal partial least squares discriminant analysisPericonceptional periodPotential confoundersUrinary concentrationsMetabolomic markersNutritional epidemiologyUnivariate statistical analysisExposure informationCritical windowUrine samplesDiscovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations
Yan H, Talty R, Jain A, Cai Y, Zheng J, Shen X, Muca E, Paty P, Bosenberg M, Khan S, Johnson C. Discovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations. Redox Biology 2023, 62: 102699. PMID: 37086630, PMCID: PMC10172914, DOI: 10.1016/j.redox.2023.102699.Peer-Reviewed Original ResearchConceptsKRAS mutant tumorsMale CRC patientsCRC patientsMale patientsKRAS mutationsMutant tumorsOverall survivalMale colorectal cancer patientsKRAS wild-type tumorsAberrant tumor metabolismColorectal cancer patientsCRC patient cohortsColorectal cancer casesFerroptosis-related genesWild-type tumorsNovel potential avenuesNormal colon tissuesPoor OSKRAS statusAdverse outcomesCRC cellsPatient cohortCancer patientsType tumorsCancer casesEarly-Onset Colorectal Cancer Somatic Gene Mutations by Population Subgroups.
Shen X, DeWan A, Johnson C. Early-Onset Colorectal Cancer Somatic Gene Mutations by Population Subgroups. Cancer Discovery 2023, 13: 530-531. PMID: 36855917, DOI: 10.1158/2159-8290.cd-22-1464.Peer-Reviewed Original ResearchIn silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer
Lu L, Ma W, Johnson C, Khan S, Irwin M, Pusztai L. In silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer. Vaccine 2023, 41: 2073-2083. PMID: 36813666, PMCID: PMC10064809, DOI: 10.1016/j.vaccine.2023.02.048.Peer-Reviewed Original ResearchConceptsMRNA vaccinesOvarian cancerT cell responsesMutation-derived neoantigensT cell epitopesSARS-CoV-2Multiple neoantigensCytotoxic CD8Dendritic cellsCA 125Cancer vaccinesPatient survivalImmune responseCell epitopesNeoepitope peptidesNeoantigensVaccineCell responsesCancerBreastReverse vaccinologyCD8CD40LIFNNeoepitopesPrenatal Choline Supplement in a Maternal Obesity Model Modulates Offspring Hepatic Lipidomes
Korsmo H, Kadam I, Reaz A, Bretter R, Saxena A, Johnson C, Caviglia J, Jiang X. Prenatal Choline Supplement in a Maternal Obesity Model Modulates Offspring Hepatic Lipidomes. Nutrients 2023, 15: 965. PMID: 36839327, PMCID: PMC9963284, DOI: 10.3390/nu15040965.Peer-Reviewed Original ResearchConceptsMetabolic-associated fatty liver diseaseMaternal choline supplementationHF feedingHepatic lipidomeCholine supplementationMale offspringFatty liver diseaseChronic metabolic diseaseSemi-essential nutrientsNervonic acidEmbryonic day 17.5MAFLD progressionMaternal obesityLiver diseaseInsulin resistanceMouse offspringObesogenic dietOffspring liverLipid overloadOffspring healthLower oxidative stressMetabolic diseasesCholine supplementsMacronutrient metabolismDay 17.5
2022
Urinary phenol concentrations and fecundability and early pregnancy loss
Vollmar A, Weinberg C, Baird D, Wilcox A, Calafat A, Deziel N, Johnson C, Jukic A. Urinary phenol concentrations and fecundability and early pregnancy loss. Human Reproduction 2022, 38: 139-155. PMID: 36346334, PMCID: PMC10089295, DOI: 10.1093/humrep/deac230.Peer-Reviewed Original ResearchConceptsEarly pregnancy lossPregnancy lossUrinary phenol concentrationsIntraclass correlation coefficientMenstrual cycleNational InstituteDaily first-morning urine specimensPhenol exposureEnvironmental Health SciencesFirst morning urine specimensLogistic regressionSTUDY FUNDING/COMPETINGMultivariable logistic regressionPARTICIPANTS/MATERIALSROLE OF CHANCEIntramural Research ProgramClinical miscarriageProspective cohortIncreased oddsLive birthsEpidemiologic studiesUrine specimensHealth SciencesEndocrine-disrupting potentialReproductive functionBile acid distributions, sex-specificity, and prognosis in colorectal cancer
Cai Y, Shen X, Lu L, Yan H, Huang H, Gaule P, Muca E, Theriot CM, Rattray Z, Rattray NJW, Lu J, Ahuja N, Zhang Y, Paty PB, Khan SA, Johnson CH. Bile acid distributions, sex-specificity, and prognosis in colorectal cancer. Biology Of Sex Differences 2022, 13: 61. PMID: 36274154, PMCID: PMC9590160, DOI: 10.1186/s13293-022-00473-9.Peer-Reviewed Original ResearchConceptsLeft-sided colon tumorsRight-sided colon tumorsColon cancer patientsColorectal cancerTumor locationBile acidsColon tumorsCancer patientsQuantitative immunofluorescencePrimary tumor locationImmune regulatory cellsRecurrence-free survivalBile acid metabolismSecondary bile acidsBile acid distributionBile acid analysisBackgroundBile acidsOverall survivalRegulatory cellsCRC patientsMale patientsPatient sexImmune cellsPatient prognosisImmune responseHemoglobin normalization outperforms other methods for standardizing dried blood spot metabolomics: A comparative study
Jain A, Morris M, Lin EZ, Khan SA, Ma X, Deziel NC, Godri Pollitt KJ, Johnson CH. Hemoglobin normalization outperforms other methods for standardizing dried blood spot metabolomics: A comparative study. The Science Of The Total Environment 2022, 854: 158716. PMID: 36113793, DOI: 10.1016/j.scitotenv.2022.158716.Peer-Reviewed Original ResearchEvaluation of the role of KPNA2 mutations in breast cancer prognosis using bioinformatics datasets
Alnoumas L, van den Driest L, Apczynski Z, Lannigan A, Johnson CH, Rattray NJW, Rattray Z. Evaluation of the role of KPNA2 mutations in breast cancer prognosis using bioinformatics datasets. BMC Cancer 2022, 22: 874. PMID: 35948941, PMCID: PMC9364282, DOI: 10.1186/s12885-022-09969-4.Peer-Reviewed Original ResearchConceptsBreast cancer prognosisBreast cancerCancer prognosisFemale cancer-related mortalityPoor patient survival outcomePrecision medicine-based approachKPNA2 overexpressionNovel chemotherapy agentsCancer-related mortalityPatient survival outcomesPoor patient prognosisAggressive tumor phenotypePatient agePrognostic rolePatient survivalSurvival outcomesPatient prognosisLeading causeChemotherapy agentsClinical dataCancer casesClinicopathologic parametersPatient stratificationActionable targetsChemotherapy resistanceNon-targeted metabolomics and associations with per- and polyfluoroalkyl substances (PFAS) exposure in humans: A scoping review
Guo P, Furnary T, Vasiliou V, Yan Q, Nyhan K, Jones DP, Johnson CH, Liew Z. Non-targeted metabolomics and associations with per- and polyfluoroalkyl substances (PFAS) exposure in humans: A scoping review. Environment International 2022, 162: 107159. PMID: 35231839, PMCID: PMC8969205, DOI: 10.1016/j.envint.2022.107159.Peer-Reviewed Original ResearchConceptsPolyfluoroalkyl substances (PFAS) exposureSubstance exposurePFAS exposureNon-pregnant adultsNon-targeted metabolomicsLiquid chromatography-mass spectrometryHigh-resolution liquid chromatography-mass spectrometryFatty acid oxidationChromatography-mass spectrometryPregnant womenBiological membrane functionMetabolic pathway alterationsEpidemiological studiesTryptophan metabolismHuman studiesMetabolomic signaturePathway alterationsLipid metabolismLipid metabolitesGlycerophospholipid metabolismProspective designHuman physiological changesMetabolomic profilesAnalytical platformMetabolome changes
2021
Kynurenic acid may underlie sex-specific immune responses to COVID-19
Cai Y, Kim DJ, Takahashi T, Broadhurst DI, Yan H, Ma S, Rattray NJW, Casanovas-Massana A, Israelow B, Klein J, Lucas C, Mao T, Moore AJ, Muenker MC, Oh JE, Silva J, Wong P, team Y, Ko AI, Khan SA, Iwasaki A, Johnson CH. Kynurenic acid may underlie sex-specific immune responses to COVID-19. Science Signaling 2021, 14: eabf8483. PMID: 34230210, PMCID: PMC8432948, DOI: 10.1126/scisignal.abf8483.Peer-Reviewed Original ResearchConceptsKynurenic acidImmune responseClinical outcomesSex-specific immune responsesT cell responsesPoor clinical outcomeCOVID-19 patientsCoronavirus disease 2019COVID-19Sex-related differencesMale patientsCytokine abundanceInflammatory cytokinesKynurenine ratioSerum metabolomeDisease 2019Sex-specific linkKynurenine aminotransferaseCell responsesOld malePatientsMalesOutcomesResponseMetabolitesYIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment
Yang X, Lam W, Jiang Z, Guan F, Han X, Hu R, Cai W, Cheng W, Liu SH, Cheng P, Cai Y, Rattray NJW, Johnson CH, Chen L, Cheng YC. YIV-906 potentiated anti-PD1 action against hepatocellular carcinoma by enhancing adaptive and innate immunity in the tumor microenvironment. Scientific Reports 2021, 11: 13482. PMID: 34188068, PMCID: PMC8242098, DOI: 10.1038/s41598-021-91623-3.Peer-Reviewed Original ResearchConceptsM1-like macrophage polarizationMacrophage polarizationIDO activityInterferon gammaInnate immunityTumor microenvironmentTraditional Chinese herbal formulationPD-L1 inductionM1-like macrophagesAdaptive immune responsesM2 macrophage polarizationChinese herbal formulationTumor bearing miceQuality of lifeAnti-tumor activityGastrointestinal symptomsMonocytic MDSCsProlong survivalImmune toleranceAcute inflammationCancer patientsClinical resultsHepatocellular carcinomaImmune responseRadiation therapyIntratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma
Zhu G, Su H, Johnson CH, Khan SA, Kluger H, Lu L. Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma. European Journal Of Cancer 2021, 151: 25-34. PMID: 33962358, PMCID: PMC8184628, DOI: 10.1016/j.ejca.2021.03.053.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBacteriaBacterial LoadBacterial TranslocationChemokinesClostridialesCytotoxicity, ImmunologicFemaleGastrointestinal MicrobiomeHumansLymphocyte CountLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedPrognosisSkin NeoplasmsT-Lymphocytes, CytotoxicTumor MicroenvironmentYoung AdultConceptsT cellsCutaneous melanomaPatient survivalGut microbiomeAdjusted hazard ratioT cell infiltrationChemokine gene expressionChemokine levelsCytotoxic CD8Hazard ratioSystemic inflammationShorter survivalCCL5 expressionPatient outcomesCD8Immune responseMortality riskGut microbiotaSurvival analysisMelanomaTumor nicheHuman cancersSurvivalSignificant correlationPositive associationIdentification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach
Charkoftaki G, Golla JP, Santos-Neto A, Orlicky DJ, Garcia-Milian R, Chen Y, Rattray NJW, Cai Y, Wang Y, Shearn CT, Mironova V, Wang Y, Johnson CH, Thompson DC, Vasiliou V. Identification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach. Toxicological Sciences 2021, 183: 338-351. PMID: 33693819, PMCID: PMC8921626, DOI: 10.1093/toxsci/kfab030.Peer-Reviewed Original ResearchConceptsDX exposureBile acid quantificationRepair responseBDF-1 miceDNA damageDose-dependent DNA damageEffects of exposureHistopathological studySubchronic exposureImmunohistochemical analysisLiver carcinogenLiver carcinogenicityLiver transcriptomicsDrinking waterMetabolomic profilingMicePotential mechanismsLiverEnvironmental chemicalsState maximum contaminant levelToxic effectsCell deathExposureOxidative stress responsePresent studyUse of Untargeted Metabolomics to Explore the Air Pollution-Related Disease Continuum
Jin L, Godri Pollitt KJ, Liew Z, Rosen Vollmar AK, Vasiliou V, Johnson CH, Zhang Y. Use of Untargeted Metabolomics to Explore the Air Pollution-Related Disease Continuum. Current Environmental Health Reports 2021, 8: 7-22. PMID: 33420964, DOI: 10.1007/s40572-020-00298-x.Peer-Reviewed Original ResearchConceptsAir pollutant exposureAdverse health effectsSpecific adverse health effectsOxidative stressHealth effectsPerturbation of metabolitesAir pollution exposureUntargeted metabolomicsPollutant exposureSteroid metabolic pathwaysPregnant womenInflammatory responseDisease continuumReviewThe purposeHealth outcomesLarger sample sizeMetabolic pathwaysDisease statusPollution exposureIdentified metabolitesMetabolic perturbationsMetabolic changesSummaryOur reviewAir pollution componentsMetabolomic analysis
2020
Gene Alterations of N6‐Methyladenosine (m6A) Regulators in Colorectal Cancer: A TCGA Database Study
Zhang Q, Cai Y, Kurbatov V, Khan SA, Lu L, Zhang Y, Johnson CH. Gene Alterations of N6‐Methyladenosine (m6A) Regulators in Colorectal Cancer: A TCGA Database Study. BioMed Research International 2020, 2020: 8826456. PMID: 33415160, PMCID: PMC7769650, DOI: 10.1155/2020/8826456.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAgedAlpha-Ketoglutarate-Dependent Dioxygenase FTOColorectal NeoplasmsDatabases, GeneticDisease-Free SurvivalDNA Copy Number VariationsFemaleGene Expression Regulation, NeoplasticGenes, NeoplasmHumansMaleMultivariate AnalysisMutationNerve Tissue ProteinsPrognosisProportional Hazards ModelsRNA Splicing FactorsRNA, MessengerConceptsDisease-free survivalImmune cell infiltrationM6A regulatorsCRC patientsCRC casesCell infiltrationMRNA expressionWorse overall survivalN6-methyladenosine regulatorsMicrosatellite instability statusMessenger RNA expressionCancer Genome AtlasOverall survivalColorectal cancerCRC tissuesDatabase studyImmune functionInstability statusColon tissuesRole of m6AGene alterationsRNA expressionCRCGenome AtlasGenetic mutationsAccounting for urinary dilution in peri-implantation samples: implications for creatinine adjustment and specimen pooling
Rosen Vollmar AK, Johnson CH, Weinberg CR, Deziel NC, Baird DD, Wilcox AJ, Jukic AMZ. Accounting for urinary dilution in peri-implantation samples: implications for creatinine adjustment and specimen pooling. Journal Of Exposure Science & Environmental Epidemiology 2020, 31: 356-365. PMID: 32424331, PMCID: PMC7671945, DOI: 10.1038/s41370-020-0227-1.Peer-Reviewed Original ResearchConceptsCreatinine adjustmentCreatinine concentrationUrinary dilutionUrinary estrogen metabolitesEffect of pregnancyUrinary creatinine concentrationCreatinine levelsWeeks' gestationEarly pregnancyCreatinine excretionEstrogen metabolitesCreatinine measuresUrine specimensPooled measureBiomarker measurementsPooled specimensEnvironmental exposuresExposure measuresLinear mixed modelsBiomonitoring resultsPregnancyT-testKappa coefficientMixed modelsPerson sample
2019
Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty
Rattray NJW, Trivedi DK, Xu Y, Chandola T, Johnson CH, Marshall AD, Mekli K, Rattray Z, Tampubolon G, Vanhoutte B, White IR, Wu FCW, Pendleton N, Nazroo J, Goodacre R. Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty. Nature Communications 2019, 10: 5027. PMID: 31690722, PMCID: PMC6831565, DOI: 10.1038/s41467-019-12716-2.Peer-Reviewed Original ResearchConceptsRisk of frailtySocial care costsSubstantial economic burdenAnalysis of serumFrailty indexGas chromatography-mass spectrometry metabolomicsMetabolic dysregulationEconomic burdenVitamin ECare costsPoor healthPopulation-level assessmentFrailtyOlder peopleLongitudinal validationMetabolic phenotypeGlobal AGEingLater lifeMultivariate regressionSignificant metabolitesCarnitine shuttleDysregulationGreater proportionHealthPhenotype