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 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 PMID: 39163853, 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 PMID: 39039782, 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 casesHepatopancreatobiliary malignancies: time to treatment matters
Kerekes D, Frey A, Bakkila B, Johnson C, Becher R, Billingsley K, Khan S. Hepatopancreatobiliary malignancies: time to treatment matters. Journal Of Gastrointestinal Oncology 2023, 0: 0-0. PMID: 37201090, PMCID: PMC10186552, DOI: 10.21037/jgo-22-1067.Peer-Reviewed Original ResearchTreatment initiationStage IHPB cancersStage I pancreatic cancerExtrahepatic bile duct cancerKaplan-Meier survival analysisHPB cancer patientsNational Cancer DatabaseRetrospective cohort studyBile duct cancerMedian treatment initiationHepatopancreatobiliary cancersMedian survivalCohort studyDuct cancerOverall survivalHispanic patientsEHBD cancerOncologic careBile ductCox regressionBlack raceCancer patientsDefinitive carePancreatic cancerEarly-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 pathwaysChemotherapySurgeryIdentifying Sex-Specific Cancer Metabolites and Associations to Prognosis
Shen X, Ma S, Khan S, Johnson C. Identifying Sex-Specific Cancer Metabolites and Associations to Prognosis. Learning Materials In Biosciences 2023, 271-299. DOI: 10.1007/978-3-031-44256-8_11.Peer-Reviewed Original ResearchMetabolomics dataSurvival analysisCancer metabolitesColorectal cancerCox proportional hazards regression analysisProportional hazards regression analysisHazards regression analysisSex-specific associationsClinical dataCancer patientsCancer prognosisCancerMetabolomicsMultiple comparisonsPrognosisAnalytical methodSurvivalOncology studiesPatientsAlternative analytical approachRegression analysisSex-specificMetabolitesSex interactionAssociation
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 response