Jason Crawford, PhD
Professor of Chemistry and of Microbial PathogenesisCards
About
Research
Overview
Medical Research Interests
Bacteria; Chemistry; Host-Pathogen Interactions
Publications
2024
Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca
Hamchand R, Wang K, Song D, Palm N, Crawford J. Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca. Nature Communications 2024, 15: 8902. PMID: 39406708, PMCID: PMC11480411, DOI: 10.1038/s41467-024-53185-6.Peer-Reviewed Original ResearchConceptsK. oxytocaGeneral carbohydrate metabolismVirulence factor productionPLP-dependent enzymesAssociated with gutEnterobactin biosynthesisAutoinducer signalBacterial virulenceKlebsiella oxytocaSpecific carbohydratesHost immune responseCarbohydrate metabolismAutoinducerMolecular signalsVirulenceHistamine receptor H4BiosynthesisHost signalAcquisition responsesProtease inhibitorsPathwayHostLung pathologyLung isolationImmune responseBacterial small molecule metabolites implicated in gastrointestinal cancer development
Turocy T, Crawford J. Bacterial small molecule metabolites implicated in gastrointestinal cancer development. Nature Reviews Microbiology 2024, 23: 106-121. PMID: 39375475, DOI: 10.1038/s41579-024-01103-4.Peer-Reviewed Original ResearchSmall molecule metabolitesGastrointestinal cancer developmentAssociated with cancer progressionHost–microorganism interactionsGastrointestinal cancerCancer riskCancer developmentCancer progressionCancerTherapeutic interventionsMicrobiome membersHuman microbiomeBacterial speciesGlobal causeMolecular mechanismsMetabolitesRiskHuman 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 GPR84GPR84Enterococcus faecalis-derived adenine enhances enterohaemorrhagic Escherichia coli Type 3 Secretion System-dependent virulence
Martins F, Rosay T, Rajan A, Carter H, Turocy T, Mejia A, Crawford J, Maresso A, Sperandio V. Enterococcus faecalis-derived adenine enhances enterohaemorrhagic Escherichia coli Type 3 Secretion System-dependent virulence. Nature Microbiology 2024, 9: 2448-2461. PMID: 38965331, PMCID: PMC11585081, DOI: 10.1038/s41564-024-01747-1.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAnimalsCoculture TechniquesEnterococcus faecalisEnterocytesEnterohemorrhagic Escherichia coliEscherichia coli InfectionsEscherichia coli ProteinsGastrointestinal MicrobiomeGene Expression Regulation, BacterialHemolysin ProteinsHost-Pathogen InteractionsHumansHypoxanthineMiceType III Secretion SystemsVirulenceVirulence FactorsXanthineConceptsT3SS gene expressionType 3 secretion systemGene expressionAE lesion formationPromote colonization resistanceE. faecalisAdenine biosynthesisEHEC virulenceEffector translocationBacterial geneticsColonization resistanceEnteric pathogensT3SSLesion formationEHECSupplementation experimentsVirulencePathway activationAdenineEnhanced pathogenesisHost responseCo-infectionExpressionCo-cultureTranscriptomeThe Xenorhabdus nematophila LrhA transcriptional regulator modulates production of γ-keto-N-acyl amides with inhibitory activity against mutualistic host nematode egg hatching
Lam Y, Hamchand R, Mucci N, Kauffman S, Dudkina N, Reagle E, Casanova-Torres Á, DeCuyper J, Chen H, Song D, Thomas M, Palm N, Goodrich-Blair H, Crawford J. The Xenorhabdus nematophila LrhA transcriptional regulator modulates production of γ-keto-N-acyl amides with inhibitory activity against mutualistic host nematode egg hatching. Applied And Environmental Microbiology 2024, 90: e00528-24. PMID: 38916293, PMCID: PMC11267870, DOI: 10.1128/aem.00528-24.Peer-Reviewed Original ResearchRegulatory hierarchyG protein-coupled receptorsSmall molecule signalsHost-bacteria interactionsSymbiotic relationshipNatural productsHuman G protein-coupled receptorsAmino acid metabolismRegulating amino acid metabolismNull mutantsDiverse natural productsSecondary metabolismNematode progeny productionPathogen interactionsGlobal regulatorNematode egg hatchingWild typeInsect hostsSecondary metabolitesHatching rateLrhAAcylated appendagesMolecular networksMolecule signalsAmide signalsMechanism of Action of KL-50, a Candidate Imidazotetrazine for the Treatment of Drug-Resistant Brain Cancers
Huseman E, Lo A, Fedorova O, Elia J, Gueble S, Lin K, Sundaram R, Oh J, Liu J, Menges F, Rees M, Ronan M, Roth J, Batista V, Crawford J, Pyle A, Bindra R, Herzon S. Mechanism of Action of KL-50, a Candidate Imidazotetrazine for the Treatment of Drug-Resistant Brain Cancers. Journal Of The American Chemical Society 2024, 146: 18241-18252. PMID: 38815248, PMCID: PMC11409917, DOI: 10.1021/jacs.3c06483.Peer-Reviewed Original ResearchDNA repair capacityDifferential DNA repair capacityDNA interstrand cross-linksRepair capacityInterstrand cross-linksDisplacement of fluorideDNA repairCross-linkingAberrant DNA repairLesionsHealthy tissueBrain cancerRing openingHealthy cellsMGMTSelective chemotherapyGenotoxic agentsTumorChemical DNA modificationsCancerMultistep processRepairProof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid
Papini C, Ullah I, Ranjan A, Zhang S, Wu Q, Spasov K, Zhang C, Mothes W, Crawford J, Lindenbach B, Uchil P, Kumar P, Jorgensen W, Anderson K. Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2320713121. PMID: 38621119, PMCID: PMC11046628, DOI: 10.1073/pnas.2320713121.Peer-Reviewed Original ResearchConceptsDirect-acting antiviralsSARS-CoV-2Lack of off-target effectsIn vitro pharmacological profileTreatment of patientsDevelopment of severe symptomsPharmacological propertiesDrug-drug interactionsSARS-CoV-2 infectionProof-of-concept studySARS-CoV-2 M<sup>pro</sup>.Combination regimenImmunocompromised patientsLead compoundsSARS-CoV-2 main proteaseOral doseActive drugTreat infectionsPharmacological profileSARS-CoV-2 MPotential preclinical candidateOff-target effectsPatientsComplete recoveryCapsule formulationIL-10 constrains sphingolipid metabolism to limit inflammation
York A, Skadow M, Oh J, Qu R, Zhou Q, Hsieh W, Mowel W, Brewer J, Kaffe E, Williams K, Kluger Y, Smale S, Crawford J, Bensinger S, Flavell R. IL-10 constrains sphingolipid metabolism to limit inflammation. Nature 2024, 627: 628-635. PMID: 38383790, PMCID: PMC10954550, DOI: 10.1038/s41586-024-07098-5.Peer-Reviewed Original ResearchActivity of RelCeramide productionVery long chainFatty acid synthesis pathwayCeramide synthase 2Fatty acid homeostasisMetabolic fluxAvailable to cellsRegulatory nodesTranscription factorsCeramide accumulationSynthesis pathwayVLC ceramidesIL-10 deficiencyGene expressionSphingolipid metabolismAcid homeostasisAberrant activationIL-10Cell types1Innate immune cellsInflammatory gene expressionCeramideSignaling resultsGenetic deletion
2023
Gut microbes modulate (p)ppGpp during a time-restricted feeding regimen
Ontai-Brenning A, Hamchand R, Crawford J, Goodman A. Gut microbes modulate (p)ppGpp during a time-restricted feeding regimen. MBio 2023, 14: e01907-23. PMID: 37971266, PMCID: PMC10746209, DOI: 10.1128/mbio.01907-23.Peer-Reviewed Original ResearchReply to: Amniote metabolism and the evolution of endothermy
Wiemann J, Menéndez I, Crawford J, Fabbri M, Gauthier J, Hull P, Norell M, Briggs D. Reply to: Amniote metabolism and the evolution of endothermy. Nature 2023, 621: e4-e6. PMID: 37673991, DOI: 10.1038/s41586-023-06412-x.Peer-Reviewed Original Research
News
News
- April 07, 2025
YCC Publications 2025
- July 11, 2024
Protein Detects and Responds to Changes in Blood Flow
- April 04, 2022Source: YaleNews
Synthetic Key Unlocks a Hidden Biology Treasure Chest
- April 01, 2022
Synthetic Key Unlocks a Hidden Biology Treasure Chest
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Institute of Biomolecular Design and Discovery
Institute of Biomolecular Design & Discovery, PO Box 27392
West Haven, CT 06516-7392
United States