2022
Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites
Cao Y, Oh J, Xue M, Huh WJ, Wang J, Gonzalez-Hernandez JA, Rice TA, Martin AL, Song D, Crawford JM, Herzon SB, Palm NW. Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites. Science 2022, 378: eabm3233. PMID: 36302024, PMCID: PMC9993714, DOI: 10.1126/science.abm3233.Peer-Reviewed Original ResearchConceptsColorectal cancerInflammatory bowel disease patientsBowel disease patientsInflammatory bowel diseaseIndigenous gut microbesBowel diseaseDisease patientsCommensal microbiotaDNA damageColon tumorigenesisElicit DNA damageGut microbesGenotoxic metabolitesGut commensalsMorganella morganiiPatientsGenotoxic chemicalsDiseaseMicrobiotaMetabolitesGenotoxicityCancerMiceFull spectrumDamage
2020
A DNA Repair Inhibitor Isolated from an Ecuadorian Fungal Endophyte Exhibits Synthetic Lethality in PTEN-Deficient Glioblastoma
Adaku N, Park HB, Spakowicz DJ, Tiwari MK, Strobel SA, Crawford JM, Rogers FA. A DNA Repair Inhibitor Isolated from an Ecuadorian Fungal Endophyte Exhibits Synthetic Lethality in PTEN-Deficient Glioblastoma. Journal Of Natural Products 2020, 83: 1899-1908. PMID: 32407116, DOI: 10.1021/acs.jnatprod.0c00012.Peer-Reviewed Original ResearchConceptsPTEN-deficient glioblastoma cellsPTEN-deficient cancersTumor suppressor PTENImportant molecular toolPTEN-deficient glioblastomaInhibitor of DNAHuman cancer developmentDNA repair inhibitorsFungal endophytesBreak repairGenomic levelSuppressor PTENMolecular toolsEndophytic fungiSynthetic lethalityPTEN deficiencyGlioblastoma cellsRepair inhibitorsCancer developmentPTEN lossCurrent cancer treatmentsLarger patient populationTherapeutic leadsMedicinal plantsNew therapeutic leads
2018
Model Colibactins Exhibit Human Cell Genotoxicity in the Absence of Host Bacteria
Shine EE, Xue M, Patel JR, Healy AR, Surovtseva YV, Herzon SB, Crawford JM. Model Colibactins Exhibit Human Cell Genotoxicity in the Absence of Host Bacteria. ACS Chemical Biology 2018, 13: 3286-3293. PMID: 30403848, PMCID: PMC7001666, DOI: 10.1021/acschembio.8b00714.Peer-Reviewed Original ResearchConceptsHost bacteriaGenotoxic secondary metabolitesDNA double-strand breaksDNA interstrandSpecific protein domainsWild-type pathwayDouble-strand breaksFull molecular mechanismsCell culturesFamily of metabolitesHuman cell linesProtein domainsPresence of membranesModule skippingCellular phenotypesExtracellular supplementationNative pathwaysHuman cell culturesMolecular mechanismsSecondary metabolitesHuman cellsColibactinEfficient DNA interstrandObserved modulesPhenotype
2016
A Mechanistic Model for Colibactin-Induced Genotoxicity
Healy AR, Nikolayevskiy H, Patel JR, Crawford JM, Herzon SB. A Mechanistic Model for Colibactin-Induced Genotoxicity. Journal Of The American Chemical Society 2016, 138: 15563-15570. PMID: 27934011, PMCID: PMC5359767, DOI: 10.1021/jacs.6b10354.Peer-Reviewed Original ResearchConceptsGene clusterE. coliDNA double-strand breaksDouble-strand breaksProbiotic Nissle 1917Clb gene clusterEukaryotic cellsCertain commensalDNA bindingProbiotic E. coliDisparate phenotypesPrecolibactinsAlkylate DNAColibactinIsolation effortsFermentation productsColiDNA alkylationDNANissle 1917Mechanistic modelSide chainsNatural productsMetabolite structuresEfficient DNA alkylation