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
Perfluorooctanesulfonic Acid and Perfluorooctanoic Acid Promote Migration of Three-Dimensional Colorectal Cancer Spheroids
Zheng J, Sun B, Berardi D, Lu L, Yan H, Zheng S, Aladelokun O, Xie Y, Cai Y, Pollitt K, Khan S, Johnson C. Perfluorooctanesulfonic Acid and Perfluorooctanoic Acid Promote Migration of Three-Dimensional Colorectal Cancer Spheroids. Environmental Science And Technology 2023, 57: 21016-21028. PMID: 38064429, DOI: 10.1021/acs.est.3c04844.Peer-Reviewed Original ResearchConceptsColorectal cancerFatty acid β-oxidationCell linesSW48 cell linesSynthesis of proteinsProgression of CRCMigration phenotypeCRC cell linesEpithelial-mesenchymal transitionThree-dimensional spheroidsMetabolic pathwaysN-cadherinΒ-oxidationMechanism of actionNovel insightsE-cadherinBiological techniquesPromotes MigrationColorectal cancer spheroidsMigration assaysMetabolic profilingKRAS G12APerfluorooctanoic acidPersistent environmental contaminantsMetabolic profilePer- and polyfluoroalkyl substances (PFAS) and thyroid hormone measurements in dried blood spots and neonatal characteristics: a pilot study
Rosen Vollmar A, Lin E, Nason S, Santiago K, Johnson C, Ma X, Godri Pollitt K, Deziel N. Per- and polyfluoroalkyl substances (PFAS) and thyroid hormone measurements in dried blood spots and neonatal characteristics: a pilot study. Journal Of Exposure Science & Environmental Epidemiology 2023, 33: 737-747. PMID: 37730931, PMCID: PMC10541328, DOI: 10.1038/s41370-023-00603-4.Peer-Reviewed Original ResearchConceptsThyroid hormone concentrationsNeonatal characteristicsThyroid hormone measurementsHormone concentrationsThyroid hormonesBlood spotsPilot studyNewborn DBSHormone measurementsPopulation-based studyThyroid hormone levelsEnvironmental risk factorsPFAS concentrationsNewborn screening testNon-parametric WilcoxonThyroid diseaseRisk factorsHormone levelsKruskal-Wallis testPFAS exposureThyroid hormone dataScreening testNeonatal DBSEnvironmental exposuresPerformance liquid chromatography-mass spectrometryMulti-omic analysis reveals metabolic pathways that characterize right-sided colon cancer liver metastasis
Morris M, Jain A, Sun B, Kurbatov V, Muca E, Zeng Z, Jin Y, Roper J, Lu J, Paty P, Johnson C, Khan S. Multi-omic analysis reveals metabolic pathways that characterize right-sided colon cancer liver metastasis. Cancer Letters 2023, 574: 216384. PMID: 37716465, PMCID: PMC10620771, DOI: 10.1016/j.canlet.2023.216384.Peer-Reviewed Original ResearchConceptsLiver metastasesColon cancer liver metastasisCancer liver metastasesSided colon cancerSubset of patientsGrowth factor betaMulti-omics analysisFatty acid oxidationMetastatic diseaseInferior survivalClinical differencesClinical behaviorUntargeted metabolomics analysisTumor behaviorColon cancerBile acidsTumor cell metabolismFactor betaPatientsMetastasisPI3K-AktReactive oxygen speciesMEK-ERKLiquid chromatography-mass spectrometryRCCUrinary 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 17.5Ferroptosis in colorectal cancer: a future target?
Yan H, Talty R, Aladelokun O, Bosenberg M, Johnson C. Ferroptosis in colorectal cancer: a future target? British Journal Of Cancer 2023, 128: 1439-1451. PMID: 36703079, PMCID: PMC10070248, DOI: 10.1038/s41416-023-02149-6.Peer-Reviewed Original ResearchConceptsColorectal cancerRegulated cell deathCurrent treatment optionsForms of RCDCancer deathTreatment optionsCRC therapyCancer recurrenceTreatment strategiesRadiation therapyOvert toxicityTherapeutic targetDrug resistanceTherapyCancer cellsFerroptosisPotential roleCancerCell deathFuture targetsDeathRecent studiesBiological pathwaysChemotherapySurgery
2022
Targeting ferroptosis to treat colorectal cancer
Yan H, Talty R, Johnson C. Targeting ferroptosis to treat colorectal cancer. Trends In Cell Biology 2022, 33: 185-188. PMID: 36473802, DOI: 10.1016/j.tcb.2022.11.003.Peer-Reviewed Original ResearchConceptsProtein kinase BArachidonic acidColorectal cancer treatmentProtein kinaseKinase BMammalian targetKey pathwaysGlutathione metabolismFerroptosis inductionEnergy metabolismCRC treatmentColorectal cancerCRC pathogenesisFerroptosisCancer treatmentPromising targetNew conceptual avenuesMetabolismTreatmentHippoKinasePrimary strategyRapamycinTargetConceptual avenuesUrinary 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 resistanceDevelopment of an Accessible Gene Expression Bioinformatics Pipeline to Study Driver Mutations of Colorectal Cancer
van den Driest L, Johnson CH, Rattray NJW, Rattray Z. Development of an Accessible Gene Expression Bioinformatics Pipeline to Study Driver Mutations of Colorectal Cancer. Alternatives To Laboratory Animals 2022, 50: 282-292. PMID: 35765262, DOI: 10.1177/02611929221107546.Peer-Reviewed Original ResearchConceptsColorectal cancerBioinformatics toolsExpression patternsKirsten rat sarcoma viral oncogene homologueNext-generation sequencing technologiesDifferential expression patternsCancer-related mortalityGenetic alterationsAdenomatous polyposis coliEffector proteinsMutational driversPrognostic significancePrognostic valueSequencing technologiesBioinformatics pipelinePatient prognosisGenetic dataB-RafColorectal tumorsNovel biomarkersColon cancerTherapeutic outcomesFrequency of mutationsAnatomical locationOncogene homologueEvaluation of Racial Disparities in Quality of Care for Patients With Gastrointestinal Tract Cancer Treated With Surgery
Bakkila BF, Kerekes D, Nunez-Smith M, Billingsley KG, Ahuja N, Wang K, Oladele C, Johnson CH, Khan SA. Evaluation of Racial Disparities in Quality of Care for Patients With Gastrointestinal Tract Cancer Treated With Surgery. JAMA Network Open 2022, 5: e225664. PMID: 35377425, PMCID: PMC8980937, DOI: 10.1001/jamanetworkopen.2022.5664.Peer-Reviewed Original ResearchConceptsGastrointestinal tract cancerNegative resection marginsTract cancerNegative surgical marginsBlack patientsAdequate lymphadenectomyWhite patientsQuality of careRacial disparitiesSurgical resectionResection marginsSurgical marginsSurgical careNational Cancer DatabaseRetrospective cohort studySite of cancerLonger median survivalHealth careStandard of careCommon age rangeSignificant racial disparitiesAdjuvant chemotherapyBiliary resectionAdjuvant therapyAdult patientsNon-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
ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody
Rattray Z, Deng G, Zhang S, Shirali A, May CK, Chen X, Cuffari BJ, Liu J, Zou P, Rattray N, Johnson CH, Dubljevic V, Campbell JA, Huttner A, Baehring JM, Zhou J, Hansen JE. ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody. JCI Insight 2021, 6: e145875. PMID: 34128837, PMCID: PMC8410084, DOI: 10.1172/jci.insight.145875.Peer-Reviewed Original ResearchConceptsBlood-brain barrierAnti-DNA autoantibodiesBrain tumorsBreast cancer brain metastasesBlood-brain barrier transportBrain tumor immunotherapyCancer brain metastasesBrain endothelial cellsEndothelial cell penetrationCNS lupusNeurotoxic autoantibodiesBrain metastasesTumor immunotherapyBarrier transportAntibody-based approachesCNS penetrationAutoantibodiesEfficacy studiesOrthotopic glioblastomaEndothelial cellsTumorsCancer cellsNucleoside fluxesActionable mechanismsKey transporters