Natasha Weiser, MD, PhD
Instructor of Laboratory MedicineCards
About
Research
Publications
2025
Enhancer activation from transposable elements in extrachromosomal DNA
Kraft K, Murphy S, Jones M, Shi Q, Bhargava-Shah A, Luong C, Hung K, He B, Li R, Park S, Montgomery M, Weiser N, Wang Y, Luebeck J, Bafna V, Boeke J, Mischel P, Boettiger A, Chang H. Enhancer activation from transposable elements in extrachromosomal DNA. Nature Cell Biology 2025, 27: 1914-1924. PMID: 41120733, PMCID: PMC12611757, DOI: 10.1038/s41556-025-01788-6.Peer-Reviewed Original ResearchConceptsTransposable elementsRepetitive elementsExtrachromosomal DNACancer cell fitnessEnhanced activityCRISPR interferenceCell fitnessInactive sequencesColorectal cancer cellsEcDNACancer phenotypeCancer cellsOncogene amplificationOncogene expressionTumor evolutionDNAIntratumour heterogeneityReporter assayAggressive cancerOncogeneCancerCRISPRLociMYCSequenceRegulation of MORC-1 is key to the CSR-1–mediated germline gene licensing mechanism in C. elegans
Kirshner J, Picard C, Weiser N, Mehta N, Feng S, Murphy V, Vakhnovetsky A, Alessi A, Xiao C, Inoki K, El Mouridi S, Frøkjær-Jensen C, Jacobsen S, Kim J. Regulation of MORC-1 is key to the CSR-1–mediated germline gene licensing mechanism in C. elegans. Science Advances 2025, 11: eado4170. PMID: 40540580, PMCID: PMC12180489, DOI: 10.1126/sciadv.ado4170.Peer-Reviewed Original ResearchA Guide to Extrachromosomal DNA: Cancer’s Dynamic Circular Genome
Weiser N, Watkins T, Chang H, Mischel P. A Guide to Extrachromosomal DNA: Cancer’s Dynamic Circular Genome. Cancer Discovery 2025, 15: 1105-1114. PMID: 40287855, PMCID: PMC12130802, DOI: 10.1158/2159-8290.cd-25-0230.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsUnified molecular approach for spatial epigenome, transcriptome, and cell lineages
Huang Y, Belk J, Zhang R, Weiser N, Chiang Z, Jones M, Mischel P, Buenrostro J, Chang H. Unified molecular approach for spatial epigenome, transcriptome, and cell lineages. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2424070122. PMID: 40249782, PMCID: PMC12037033, DOI: 10.1073/pnas.2424070122.Peer-Reviewed Original ResearchConceptsMitochondrial DNA variantsCell lineagesDNA copy numberAccessible chromatinDNA variantsHuman glioblastoma specimensCellular statesCopy numberSpatial assaysMolecular approachesEpigenomeLineagesMultiomicsGlioblastoma specimensCellsChromatinTranscriptomeGenesSequenceVariantsAssayTumor microenvironmentData modalities
2024
Enhancing transcription–replication conflict targets ecDNA-positive cancers
Tang J, Weiser N, Wang G, Chowdhry S, Curtis E, Zhao Y, Wong I, Marinov G, Li R, Hanoian P, Tse E, Mojica S, Hansen R, Plum J, Steffy A, Milutinovic S, Meyer S, Luebeck J, Wang Y, Zhang S, Altemose N, Curtis C, Greenleaf W, Bafna V, Benkovic S, Pinkerton A, Kasibhatla S, Hassig C, Mischel P, Chang H. Enhancing transcription–replication conflict targets ecDNA-positive cancers. Nature 2024, 635: 210-218. PMID: 39506153, PMCID: PMC11540844, DOI: 10.1038/s41586-024-07802-5.Peer-Reviewed Original ResearchConceptsTranscription-replication conflictsSingle-stranded DNATranscription-replicationReplication stressS-phase checkpoint kinaseTranscription-dependent mannerSustained tumor regressionDNA damage repairTumor cell deathDNA double strand breaksGastric cancer modelStepwise analysisGenome evolutionDouble strand breaksChromosomal lociExtrachromosomal DNAOncogenic cargoRNA transcriptsNucleotide incorporationTumor regressionCheckpoint kinaseSynthetic lethalityEcDNACancer modelsChk1 inhibitionOrigins and impact of extrachromosomal DNA
Bailey C, Pich O, Thol K, Watkins T, Luebeck J, Rowan A, Stavrou G, Weiser N, Dameracharla B, Bentham R, Lu W, Kittel J, Yang S, Howitt B, Sharma N, Litovchenko M, Salgado R, Hung K, Cornish A, Moore D, Houlston R, Bafna V, Chang H, Nik-Zainal S, Kanu N, McGranahan N, Flanagan A, Mischel P, Jamal-Hanjani M, Swanton C. Origins and impact of extrachromosomal DNA. Nature 2024, 635: 193-200. PMID: 39506150, PMCID: PMC11540846, DOI: 10.1038/s41586-024-08107-3.Peer-Reviewed Original ResearchConceptsTumor T-cell infiltrationHomologous recombination repair deficiencyAssociated with tumor stageT cell infiltrationLymphocyte-mediated immunityShorter overall survivalAssociated with metastasisTissue of originOverall survivalTumor stageCytotoxic treatmentTargeted therapyTreatment resistanceTumor typesImmune effector processTumor samplesPoor outcomeTobacco exposureImmunomodulatory genesTumorInflammatory genesClinical problemImmune systemRepair deficiencyExtrachromosomal DNA
2022
Targeted profiling of human extrachromosomal DNA by CRISPR-CATCH
Hung K, Luebeck J, Dehkordi S, Colón C, Li R, Wong I, Coruh C, Dharanipragada P, Lomeli S, Weiser N, Moriceau G, Zhang X, Bailey C, Houlahan K, Yang W, González R, Swanton C, Curtis C, Jamal-Hanjani M, Henssen A, Law J, Greenleaf W, Lo R, Mischel P, Bafna V, Chang H. Targeted profiling of human extrachromosomal DNA by CRISPR-CATCH. Nature Genetics 2022, 54: 1746-1754. PMID: 36253572, PMCID: PMC9649439, DOI: 10.1038/s41588-022-01190-0.Peer-Reviewed Original ResearchConceptsTarget enrichmentExtrachromosomal DNAPhasing of genetic variantsPulsed field gel electrophoresisBase-pair resolutionHuman cancer cellsChromosomal DNANanopore sequencingChromosomal segmentsMethylation profilesGenetic variantsCRISPR-Cas9 treatmentGel electrophoresisEcDNAEGFR promoterHuman metastatic melanomaCancer cellsDNAOncogene amplificationSequenceTherapeutic resistanceExcision modelMetastatic melanomaEGFRvIII mutationGlioblastoma modelOncogene Convergence in Extrachromosomal DNA Hubs
Weiser N, Hung K, Chang H. Oncogene Convergence in Extrachromosomal DNA Hubs. Cancer Discovery 2022, 12: of1-of4. PMID: 35398879, PMCID: PMC9302380, DOI: 10.1158/2159-8290.cd-22-0076.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2021
ecDNA hubs drive cooperative intermolecular oncogene expression
Hung K, Yost K, Xie L, Shi Q, Helmsauer K, Luebeck J, Schöpflin R, Lange J, Chamorro González R, Weiser N, Chen C, Valieva M, Wong I, Wu S, Dehkordi S, Duffy C, Kraft K, Tang J, Belk J, Rose J, Corces M, Granja J, Li R, Rajkumar U, Friedlein J, Bagchi A, Satpathy A, Tjian R, Mundlos S, Bafna V, Henssen A, Mischel P, Liu Z, Chang H. ecDNA hubs drive cooperative intermolecular oncogene expression. Nature 2021, 600: 731-736. PMID: 34819668, PMCID: PMC9126690, DOI: 10.1038/s41586-021-04116-8.Peer-Reviewed Original ResearchConceptsEcDNA hubsPVT1 promoterEnhancer-gene interactionsCis-regulatory elementsDiverse cancer cell typesCancer cell typesExpression of MYCCRISPR interferenceColorectal cancer cell linesExpression of oncogenesTranscriptional regulationExtrachromosomal DNAActive genesCancer cell linesOncogene locusBET inhibitor JQ1Gene activationEcDNAGene inductionGenesOncogenic functionExtraterminal domainGene amplificationOncogene overexpressionSystematic silencing
2019
Genotype–phenotype analysis of 523 patients by genetics evaluation and clinical exome sequencing
Ziats M, Ahmad A, Bernat J, Fisher R, Glassford M, Hannibal M, Jacher J, Weiser N, Keegan C, Lee K, Marzulla T, O’Connor B, Quinonez S, Seemann L, Turner L, Bielas S, Harris N, Ogle J, Innis J, Martin D. Genotype–phenotype analysis of 523 patients by genetics evaluation and clinical exome sequencing. Pediatric Research 2019, 87: 735-739. PMID: 31618753, PMCID: PMC7082194, DOI: 10.1038/s41390-019-0611-5.Peer-Reviewed Original ResearchConceptsClinical exome sequencingExome sequencingClinical genetics teamGenotype-phenotype analysisPediatric genetics clinicMultiple organ system involvementGenetics teamPathogenic mutationsMultiple congenital anomaliesOrgan system involvementAbsence of abnormalitiesGenetics clinicClinical pediatric practiceCongenital anomaliesGenetics referralSystem abnormalitiesSystem involvementGenetic evaluationGeneticsDevelopmental delayPatientsSequenceMichigan MedicinePhenotypeVariants