2025
Distinct metabolic and genetic alterations in tumors from early-onset versus late-onset colorectal cancer
Janak A, Jain A, Garcia-Milian R, Aladelokun O, Ma X, Paty P, Khan S, Johnson C. Distinct metabolic and genetic alterations in tumors from early-onset versus late-onset colorectal cancer. Free Radical Biology And Medicine 2025, 240: 773-782. PMID: 40865779, DOI: 10.1016/j.freeradbiomed.2025.08.052.Peer-Reviewed Original ResearchLate-onset colorectal cancerEO-CRCColorectal cancerTumor metabolomeMass spectrometry-based untargeted metabolomicsTumor tissuesCatecholamine metabolismGroup of CRC patientsMetabolite set enrichment analysisPatient-matched normal tissuesTumor-specific differencesEarly-onset colorectal cancerMetabolite of dopaminePD-L1Untargeted metabolomicsCRC patientsOxidative stress-related genesHomovanillic acidGenetic alterationsEarly-onsetTumorTherapeutic strategiesGene expression validationNormal tissuesEGFR SignalingDiscovery of a Widespread Polyamine–Low-Molecular-Weight Thiol Hybrid Pathway in Clostridioides difficile
Hunt R, Oh J, Jain A, Kuo T, Berardi D, Jian W, Song D, Wu Q, Goodman A, Palm N, Zimmermann M, Johnson C, Crawford J. Discovery of a Widespread Polyamine–Low-Molecular-Weight Thiol Hybrid Pathway in Clostridioides difficile. ACS Infectious Diseases 2025, 11: 2246-2264. PMID: 40671632, PMCID: PMC12403189, DOI: 10.1021/acsinfecdis.5c00286.Peer-Reviewed Original ResearchConceptsLow-molecular-weight thiolsTwo-gene operonBacteroides uniformisExpression of polyaminesAssociated with diseaseColorectal cancerBiosynthesis genesCommunity-level changesClostridioides difficile infectionGut homeostasisGenetic screeningGI mucosal biopsiesRisk of colorectal cancerHybrid pathwayMicrobial metabolismHybrid metabolitesGastrointestinal (GI) tractClostridioides difficileDiverse collectionHost immunityMucosal biopsiesSevere inflammationGenesCationic metabolitesMucolytic agentSenescence Cell Induction Methods Display Diverse Metabolic Reprogramming and Reveal an Underpinning Serine/Taurine Reductive Metabolic Phenotype
Berardi D, Farrell G, AlSultan A, McCulloch A, Hall N, Sousa R, Jimenez M, Selman C, Bellantuono I, Johnson C, Rattray Z, Rattray N. Senescence Cell Induction Methods Display Diverse Metabolic Reprogramming and Reveal an Underpinning Serine/Taurine Reductive Metabolic Phenotype. Aging Cell 2025, 24: e70127. PMID: 40530891, PMCID: PMC12341781, DOI: 10.1111/acel.70127.Peer-Reviewed Original ResearchSenescence inductionLabel-free proteomicsDNA damage markersRedox circuitsCell inductionImpaired proteostasisP21 levelsTherapeutic strategiesCellular phenotypesMetabolic phenotypeMetabolic reprogrammingProteomic heterogeneityMetabolic shiftSenescence markersProteomic profilingMetabolic processesSenescence biomarkersDamage markersProtein levelsSenescenceSubphenotypesSenescence modelInfluence cellsPhenotypeInductionMapping pesticide-induced metabolic alterations in human gut bacteria
Chen L, Yan H, Di S, Guo C, Zhang H, Zhang S, Gold A, Wang Y, Hu M, Wu D, Johnson C, Wang X, Zhu J. Mapping pesticide-induced metabolic alterations in human gut bacteria. Nature Communications 2025, 16: 4355. PMID: 40348778, PMCID: PMC12065874, DOI: 10.1038/s41467-025-59747-6.Peer-Reviewed Original ResearchConceptsModulating gut microbiota compositionGut bacteria speciesGut microbial speciesHuman gut bacteriaGut microbiota compositionGut bacterial metabolismPesticide exposureHost healthGut bacteriaMicrobiota compositionMicrobial speciesBacterial metabolismBacteria speciesMolecular mechanismsComprehensive atlasLipid metabolismGutIn Vivo Mouse ModelPesticidesHostMetabolismSpeciesInteractive atlasMouse modelMetabolic changesSex-specific effects of exogenous asparagine on colorectal tumor growth, 17β-estradiol levels, and aromatase
Aladelokun O, Benitez K, Wang Y, Jain A, Berardi D, Maroun G, Shen X, Roper J, Gibson J, Sumigray K, Khan S, Johnson C. Sex-specific effects of exogenous asparagine on colorectal tumor growth, 17β-estradiol levels, and aromatase. Pharmacological Research 2025, 215: 107736. PMID: 40228761, PMCID: PMC12100670, DOI: 10.1016/j.phrs.2025.107736.Peer-Reviewed Original ResearchTumor-specific survivalColorectal cancerTumor growthR2G2 miceIncreased serum estradiol levelsSerum estradiol levelsSub-populations of macrophagesAssociated with cancer prognosisSuppressed tumor growthColorectal tumor growthExogenous asparagineColorectal cancer developmentColorectal cancer cellsNegative feed-back effectEstradiol levelsGlutamate levelsSex-related differencesSex-specific effectsMale miceCancer prognosisAsparagine supplementationCancer progressionMiceDecreased numberTumorQuality of gastrointestinal surgical oncology care according to insurance status
Butensky S, Kerekes D, Bakkila B, Billingsley K, Ahuja N, Johnson C, Khan S. Quality of gastrointestinal surgical oncology care according to insurance status. Journal Of Gastrointestinal Surgery 2025, 29: 101961. PMID: 39800081, DOI: 10.1016/j.gassur.2025.101961.Peer-Reviewed Original ResearchConceptsMedicare-insured patientsNational Cancer DatabaseAdequate lymphadenectomyNegative marginsCancer DatabaseRetrospective study of adult patientsStudy of adult patientsSurvival analysisInsurance statusReceipt of lymphadenectomyCurative-intent resectionGastrointestinal (GI) cancersIncreased risk of deathMultivariate survival analysisAdequacy of lymphadenectomyCox proportional hazards modelsRisk of deathProportional hazards modelResection marginsSurgical oncology careAdjuvant therapyRetrospective studyAdult patientsBiliary organismsLymphadenectomyAcetaminophen Use in Pregnancy: A Comparison of Self-Reported Intake with Maternal and Newborn Biomarker Measures
Guo P, Johnson C, Yan H, Xiao J, Dennis C, Pierce K, DeWan A, Liew Z. Acetaminophen Use in Pregnancy: A Comparison of Self-Reported Intake with Maternal and Newborn Biomarker Measures. Clinical Epidemiology 2025, 17: 1-6. PMID: 39781206, PMCID: PMC11705965, DOI: 10.2147/clep.s484953.Peer-Reviewed Original Research
2024
OncoSexome: the landscape of sex-based differences in oncologic diseases
Shen X, Zhang Y, Li J, Zhou Y, Butensky S, Zhang Y, Cai Z, DeWan A, Khan S, Yan H, Johnson C, Zhu F. OncoSexome: the landscape of sex-based differences in oncologic diseases. Nucleic Acids Research 2024, 53: d1443-d1459. PMID: 39535034, PMCID: PMC11701605, DOI: 10.1093/nar/gkae1003.Peer-Reviewed Original ResearchLongitudinal biomonitoring of mycotoxin exposure during pregnancy in the Yale Pregnancy Outcome Prediction Study
Krausová M, Ayeni K, Gu Y, Borutzki Y, O'Bryan J, Perley L, Silasi M, Wisgrill L, Johnson C, Warth B. Longitudinal biomonitoring of mycotoxin exposure during pregnancy in the Yale Pregnancy Outcome Prediction Study. Environment International 2024, 194: 109081. PMID: 39615253, DOI: 10.1016/j.envint.2024.109081.Peer-Reviewed Original ResearchPregnancy Outcome Prediction studyPregnant womenOutcome prediction studiesTandem mass spectrometryLiquid chromatography tandem mass spectrometryPlasma matrixUrine methodMass spectrometryUrinary dataHuman biomonitoringCarcinogen ochratoxin ASerum methodNeoplastic effectsSerumLC-MS/MSMonomethyl etherUnborn childSerum samplesTime pointsUrineBiomarkers of exposurePregnancyAdverse health effectsWomenHuman biomonitoring guidance valuesCharting 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 mapCancerTumorHuman AKR1C3 binds agonists of GPR84 and participates in an expanded polyamine pathway
Dudkina N, Park H, Song D, Jain A, Khan S, Flavell R, Johnson C, Palm N, Crawford J. Human AKR1C3 binds agonists of GPR84 and participates in an expanded polyamine pathway. Cell Chemical Biology 2024, 32: 126-144.e18. PMID: 39163853, PMCID: PMC11748234, DOI: 10.1016/j.chembiol.2024.07.011.Peer-Reviewed Original ResearchHuman aldo-keto reductase family 1 member C3Mammalian fatty acid synthaseDNA double-strand break responseDouble-strand break responseAldo-keto reductase family 1 member C3Associated with poor prognosisPolyamine pathwayFatty acid synthesisFatty acid synthaseAcid synthaseAKR1C3 activityPoor prognosisBiochemical roleAcid synthesisClinical significanceLigand screeningFerroptosis resistanceDNA damageAKR1C3Metabolic diseasesDiverse cancersDNANADPHAgonists of GPR84GPR84Asparagine synthetase and G‐protein coupled estrogen receptor are critical responders to nutrient supply in KRAS mutant colorectal cancer
Lu L, Zhang Q, Aladelokun O, Berardi D, Shen X, Marin A, Garcia‐Milian R, Roper J, Khan S, Johnson C. Asparagine synthetase and G‐protein coupled estrogen receptor are critical responders to nutrient supply in KRAS mutant colorectal cancer. International Journal Of Cancer 2024, 156: 52-68. PMID: 39039782, PMCID: PMC11537827, DOI: 10.1002/ijc.35104.Peer-Reviewed Original ResearchG protein-coupled estrogen receptor 1KRAS mutant colorectal cancerAsparagine synthetase expressionMutant colorectal cancerColorectal cancerAsparagine synthetaseG-protein coupled estrogen receptor 1 expressionG protein-coupled estrogen receptorWild-typeAssociated with poor overall survivalAdvanced stage tumorsKRAS wild-typeProtective effect of estradiolEffects of estradiolPoor overall survivalEstrogen receptor 1Expression of asparagine synthetasePresence of estradiolIncreased caspase-3 activityDepletion inhibited cell growthColon cancer cohortNutrient supplyAdvanced tumorsOverall survivalStage tumorsGrowth 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 synthetaseTransacylation and hydrolysis of the acyl glucuronides of ibuprofen and its α-methyl-substituted analogues investigated by 1H NMR spectroscopy and computational chemistry: Implications for drug design
Richards S, Bradshaw P, Johnson C, Stachulski A, Athersuch T, Nicholson J, Lindon J, Wilson I. Transacylation and hydrolysis of the acyl glucuronides of ibuprofen and its α-methyl-substituted analogues investigated by 1H NMR spectroscopy and computational chemistry: Implications for drug design. Journal Of Pharmaceutical And Biomedical Analysis 2024, 246: 116238. PMID: 38805849, DOI: 10.1016/j.jpba.2024.116238.Peer-Reviewed Original ResearchAcyl migrationDensity functional theoryAcyl glucuronideBuffered aqueous solutionIndividual rate constantsNMR spectroscopyTransition stateComputational chemistryFunctional theoryPositional isomersHPLC-MS studiesDimethyl analoguesRate constantsDrug metabolitesHydrolysis reactionAqueous solutionDrug designActivation energySpontaneous acyl migrationAnomerisationHuman plasmaHPLC-MSTransacylation reactionAcylTransacylationA gap analysis of UK biobank publications reveals SNPs associated with intrinsic subtypes of breast cancer
van den Driest L, Kelly P, Marshall A, Johnson C, Lasky-Su J, Lannigan A, Rattray Z, Rattray N. A gap analysis of UK biobank publications reveals SNPs associated with intrinsic subtypes of breast cancer. Computational And Structural Biotechnology Journal 2024, 23: 2200-2210. PMID: 38817965, PMCID: PMC11137368, DOI: 10.1016/j.csbj.2024.05.001.Peer-Reviewed Original ResearchBreast cancerUK Biobank dataBreast cancer researchPatient stratificationVariants associated with breast cancerGenetic variants associated with breast cancerIntrinsic subtypes of breast cancerBiobank dataDied of breast cancerPrediction of tumor behaviorSubtypes of breast cancerProfiling of breast cancerPrognosis of breast cancerMeta-analysisBreast cancer subtypesImprove patient stratificationAnalysis of metabolomicsBreast cancer genesUK Biobank studyUK Biobank cohortAnalysis of breast cancerAnalysis of UK Biobank dataGlobal cancer burdenBreast cancer diagnosisCancer research
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 cases
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