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
Discovery 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 ResearchPrenatal 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 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 patients
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 malePatientsMalesOutcomesResponseMetabolitesIntratumour 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 association
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 mutations
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
2017
Exposome-Scale Investigations Guided by Global Metabolomics, Pathway Analysis, and Cognitive Computing
Warth B, Spangler S, Fang M, Johnson CH, Forsberg EM, Granados A, Martin RL, Domingo-Almenara X, Huan T, Rinehart D, Montenegro-Burke JR, Hilmers B, Aisporna A, Hoang LT, Uritboonthai W, Benton HP, Richardson SD, Williams AJ, Siuzdak G. Exposome-Scale Investigations Guided by Global Metabolomics, Pathway Analysis, and Cognitive Computing. Analytical Chemistry 2017, 89: 11505-11513. PMID: 28945073, DOI: 10.1021/acs.analchem.7b02759.Peer-Reviewed Original ResearchConceptsUnique small moleculesChemical structureStraightforward elucidationSmall moleculesExposomics researchBiotransformation productsFood contaminantsComprehensive exposure assessmentSpecific biological effectsPotential toxicantsBiological effectsToxic effectsPathway analysisConcurrent exposureHuman healthMoleculesEnvironmental exposuresGlobal metabolomicsEnvironmental toxicantsMetabolomicsContaminantsExposure assessmentWide varietyElucidationToxicants
2015
Metabolism Links Bacterial Biofilms and Colon Carcinogenesis
Johnson CH, Dejea CM, Edler D, Hoang LT, Santidrian AF, Felding BH, Ivanisevic J, Cho K, Wick EC, Hechenbleikner EM, Uritboonthai W, Goetz L, Casero RA, Pardoll DM, White JR, Patti GJ, Sears CL, Siuzdak G. Metabolism Links Bacterial Biofilms and Colon Carcinogenesis. Cell Metabolism 2015, 21: 891-897. PMID: 25959674, PMCID: PMC4456201, DOI: 10.1016/j.cmet.2015.04.011.Peer-Reviewed Original ResearchConceptsColon cancer metabolismBacterial biofilm structuresBacterial biofilmsColon cancer growthMicrobial biofilmsCancer metabolismMetabolite poolsHost tissue microenvironmentBiofilm structureCellular proliferationNormal tissuesTissue microenvironmentCancer developmentBiofilmsCancer growthMucosal biofilmsPolyamine metabolitesDiacetylspermine levelsCancer metabolomeCancer hostsAntibiotic treatmentColon carcinogenesisColon cancerColon tissuesMetabolic influences
2012
Novel metabolites and roles for α-tocopherol in humans and mice discovered by mass spectrometry–based metabolomics
Johnson CH, Slanař O, Krausz KW, Kang DW, Patterson AD, Kim JH, Luecke H, Gonzalez FJ, Idle JR. Novel metabolites and roles for α-tocopherol in humans and mice discovered by mass spectrometry–based metabolomics. American Journal Of Clinical Nutrition 2012, 96: 818-830. PMID: 22952181, PMCID: PMC3441109, DOI: 10.3945/ajcn.112.042929.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlpha-TocopherolAmino AcidsAnimalsCholesterolChromansChromatography, High Pressure LiquidFemaleGlucuronidesHumansLiverMaleMetabolomicsMiceMice, Inbred C57BLMolecular StructureSpecies SpecificitySpectrometry, Mass, Electrospray IonizationTaurineVitamin E DeficiencyYoung AdultConceptsVitamin EUrinary metabolitesMass spectrometry-based metabolomicsNovel urinary metaboliteLiver fatty acidLiver cholesterolC57BL/6 miceChronic diseasesClinical trialsΑ-tocopherolMouse modelNovel metabolitesVitamin E.Human volunteersDietary supplementsUltraperformance liquid chromatographyMiceSerum samplesInterindividual variationLiver samplesDosingSerumUrineFatty acidsMetabolites