Seth Herzon, PhD
Milton Harris ’29 Ph.D. Professor of ChemistryCards
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Milton Harris ’29 Ph.D. Professor of Chemistry
Biography
Seth Herzon completed his undergraduate studies at Temple University, obtained a PhD in 2006 from Harvard University under the guidance of Professor Andrew G. Myers, and was an NIH postdoctoral fellow with Professor John F. Hartwig at the University of Illinois, Urbana–Champaign. He began at Yale in 2008 and is currently the Milton Harris ’29 Ph.D. Professor of Chemistry. He holds joint appointments in the Departments of Pharmacology and Therapeutic Radiology at the Yale School of Medicine and is a Member of the Yale Cancer Center. Herzon's research is centered on organic synthesis with an emphasis on the molecular mechanism of action and structure–function studies of anticancer and microbiome-derived secondary metabolites. In 2021 he co-founded the oncology company Modifi Biosciences, which was acquired by Merck and Company in the Fall of 2024. From 2018–2023 he served as an Associate Editor for The Journal of Organic Chemistry.
He has been recognized for his accomplishments by a number of awards, including an NSF CAREER Award, a Searle Scholar Award, a Fellowship from the David and Lucile Packard Foundation, a Fellowship from the Alfred P. Sloan Foundation, a Cottrell Scholar Award of the Research Corporation for Scientific Advancement, a Research Scholar Award from the American Cancer Society, the Arthur C. Cope Scholar Award of the American Chemical Society, the Novartis Chemistry Lectureship, the Synthesis/Synlett Award in Organic Chemistry, the Elias J. Corey Award for Outstanding Original Contribution in Organic Synthesis by a Young Investigator, the Thieme–IUPAC Award, the Tetrahedron Young Investigator Award in Organic Synthesis, the Wilson Prize, a Yale Faculty Innovation Award, a Creativity Extension Award from the National Science Foundation, and the ACS Award for Creative Work in Synthetic Organic Chemistry. From 2018–2019 he was a member of the United States Defense Science Study Group, Sponsored by the Institute for Defense Analyses.
Appointments
Chemistry
ProfessorPrimaryPharmacology
ProfessorSecondaryTherapeutic Radiology
ProfessorSecondary
Other Departments & Organizations
- Chemistry
- Developmental Therapeutics
- Discovery to Cure Internship
- Pharmacology
- Radiobiology
- Therapeutic Radiology
- Yale Cancer Center
- Yale CTAP
Education & Training
- Postdoctoral Fellow
- University of Illinois, Urbana–Champaign (2008)
- PhD
- Harvard University, Organic Chemistry
- BS (Hon)
- Temple University, Chemistry (2002)
Research
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Overview
Research in my laboratory focuses on the total synthesis of complex secondary metabolites, with an emphasis on the synthesis and study of complex genotoxic natural products. We leverage our synthetic chemistry to elucidate the molecular basis of the phenotypic effects of the isolates. We also aim to develop new synthetic methods of general utility to overcome obstacles we encounter in our synthetic efforts. My laboratory has also studied host–microbe interactions with a focus on colibactin, a gut microbiome metabolite that induces colorectal cancer. Studies of DNA damage naturally lead to studies of DNA repair, and this line of inquiry has led me to develop novel chemotherapies to exploit tumor-associated DNA repair defects. Finally we have projects aimed at developing novel antibacterial agents.
ORCID
0000-0001-5940-9853- View Lab Website
Herzon Laboratory
Research at a Glance
Yale Co-Authors
Anna Marie Pyle, PhD
James Elia
Jason Crawford, PhD
Ranjit S. Bindra, MD, PhD
Susan Gueble, MD, PhD
Publications
2025
Total Synthesis of Chartelline C
Bartfield N, Alexander B, Herzon S. Total Synthesis of Chartelline C. Journal Of The American Chemical Society 2025, 147: 24921-24931. PMID: 40591926, DOI: 10.1021/jacs.5c07148.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAcid-catalyzed eliminationSulfur-based nucleophilesCytotoxic marine alkaloidSolid-state reactionStereocontrolled constructionBasic aluminaPhotolytic conditionsTransfer agentMarine alkaloidsOxide structurePhotolytic processC12-ketoneEnergy transferMacrolactamEnamidesIsomerizationHalogenC2-C3ChlorineBiological activitySynthesisIndolenineNucleophilesCarbinolamideBromoindolenineStructural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin
Kim M, Kim J, Lee G, Olinares P, Airan Y, Chow J, Park J, Jeong Y, Park J, Chait B, Herzon S, Kim C, Kang J. Structural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin. Structure 2025, 33: 1208-1223.e5. PMID: 40381618, DOI: 10.1016/j.str.2025.04.017.Peer-Reviewed Original ResearchCitationsConceptsNRPS-PKSCarrier proteinCryo-EM structurePKS enzymesPolyketide synthaseBiosynthesis mechanismBiosynthetic enzymesUpstream enzymesDimer interfaceColibactinBinding sitesDocking interactionsKetosynthasePromote colorectal cancerEnzymeStructural studiesGenomeBiosynthesisStructural detailsStructural analysisProteinGenotoxinsSynthaseHostCLBIGenome-scale CRISPR/Cas9 screening reveals the role of PSMD4 in colibactin-mediated cell cycle arrest
Dougherty M, Hoffmann R, Hernandez M, Airan Y, Gharaibeh R, Herzon S, Yang Y, Jobin C. Genome-scale CRISPR/Cas9 screening reveals the role of PSMD4 in colibactin-mediated cell cycle arrest. MSphere 2025, 10: e00692-24. PMID: 39918307, PMCID: PMC11934320, DOI: 10.1128/msphere.00692-24.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCell cycle arrestCycle arrestCRISPR/Cas9 screenDNA damageGenome-scale CRISPR/Cas9 screensGenome-wide CRISPR/Cas9 knockout screenRegulating cell cycle arrestRNA polymerase IIIRNA processing factorsCRISPR/Cas9 knockout screenG2-M cell cycle arrestGenotoxic secondary metabolitesHT-29 cellsHost response pathwaysPolymerase IIIKnockout screenHost pathwaysCell fateProteasome subunitsColony sizeColibactin-producing bacteriaColibactinRNA sequencingColony formation rateGene expressionA Stereoselective Oxidative Dimerization En Route to (−)-Lomaiviticin A
DiBello M, Xu Z, Palazzo A, Herzon S. A Stereoselective Oxidative Dimerization En Route to (−)-Lomaiviticin A. Organic Letters 2025, 27: 937-941. PMID: 39846772, PMCID: PMC11883818, DOI: 10.1021/acs.orglett.4c04098.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and Concepts
2024
Colibactin Exerts Androgen-dependent and -independent Effects on Prostate Cancer
Agrawal R, Al-Hiyari S, Hugh-White R, Hromas R, Patel Y, Williamson E, Mootor M, Gonzalez A, Fu J, Haas R, Jordan M, Wickes B, Mohammed G, Tian M, Doris M, Jobin C, Wernke K, Pan Y, Yamaguchi T, Herzon S, Boutros P, Liss M. Colibactin Exerts Androgen-dependent and -independent Effects on Prostate Cancer. European Urology Oncology 2024, 8: 716-730. PMID: 39547899, PMCID: PMC12075626, DOI: 10.1016/j.euo.2024.10.015.Peer-Reviewed Original ResearchCitationsAltmetricConceptsProstate cancerInduction of genomic instabilityPC diagnosisPC etiologyColibactin-producing Escherichia coliEtiology of prostate cancerProstate cancer cellsProstate cancer diagnosisSomatic point mutationsCombination in vitroGenomic instabilityAndrogen-dependentColon cancerPatient populationProstateClinical cohortInitial cancerSomatic mutationsCancer cellsDihydrotestosteroneGenetic dysfunctionSingle cell lineCancerCell linesDiagnosisIntramolecular oxyalkylation of unactivated alkenes
Xu Z, Airan Y, Tomanik M, Yang A, Bhak N, Herzon S. Intramolecular oxyalkylation of unactivated alkenes. Tetrahedron 2024, 161: 134070. PMID: 38911481, PMCID: PMC11192504, DOI: 10.1016/j.tet.2024.134070.Peer-Reviewed Original ResearchAltmetricMechanism 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 ResearchCitationsAltmetricConceptsDNA 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 processRepair1073 GENOME-SCALE CRISPR/CAS9 SCREENING REVEALS THE ROLE OF PSMD4 IN COLIBACTIN-MEDIATED CELL CYCLE ARREST
Dougherty M, Hoffmann R, Airan Y, Gharaibeh R, Herzon S, Yang Y, Jobin C. 1073 GENOME-SCALE CRISPR/CAS9 SCREENING REVEALS THE ROLE OF PSMD4 IN COLIBACTIN-MEDIATED CELL CYCLE ARREST. Gastroenterology 2024, 166: s-253. DOI: 10.1016/s0016-5085(24)01066-7.Peer-Reviewed Original ResearchAn oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids
Alexander B, Bartfield N, Gupta V, Mercado B, Del Campo M, Herzon S. An oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids. Science 2024, 383: 849-854. PMID: 38386756, DOI: 10.1126/science.adl6163.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsFunctional group manipulationsMicrocrystal electron diffractionOxidative photocyclizationAdvanced intermediateGroup manipulationsHeterocyclic residuesOxide ringSynthetic accessibilityElectron diffractionTarget identification studiesReactive alkenesModular assemblyCytotoxic alkaloidFlexible routeAlkenesIdentification studiesAlkaloidsPhotocycleDiffractionStructural complexityStructureRingIntermediateChemistrySynthesis
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