2024
Machine-guided design of cell-type-targeting cis-regulatory elements
Gosai S, Castro R, Fuentes N, Butts J, Mouri K, Alasoadura M, Kales S, Nguyen T, Noche R, Rao A, Joy M, Sabeti P, Reilly S, Tewhey R. Machine-guided design of cell-type-targeting cis-regulatory elements. Nature 2024, 634: 1211-1220. PMID: 39443793, PMCID: PMC11525185, DOI: 10.1038/s41586-024-08070-z.Peer-Reviewed Original ResearchConceptsCis-regulatory elementsCell typesActivation of off-target cellsGene expressionCell type-specific expressionSynthetic cis-regulatory elementsCell-type specificityHuman genomeUnique cell typeTissue identityBiotechnological applicationsTissue specificityIn vitro validationCell linesCre activitySequenceGenesNatural sequenceDevelopmental timeExpressionCellsGenomeTested in vivoMotifOff-target cellsSomatic mosaicism in schizophrenia brains reveals prenatal mutational processes
Maury E, Jones A, Seplyarskiy V, Nguyen T, Rosenbluh C, Bae T, Wang Y, Abyzov A, Khoshkhoo S, Chahine Y, Zhao S, Venkatesh S, Root E, Voloudakis G, Roussos P, Network B, Park P, Akbarian S, Brennand K, Reilly S, Lee E, Sunyaev S, Walsh C, Chess A. Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes. Science 2024, 386: 217-224. PMID: 39388546, PMCID: PMC11490355, DOI: 10.1126/science.adq1456.Peer-Reviewed Original ResearchConceptsTranscription factor binding sitesWhole-genome sequencingOpen chromatinMutational processesSomatic mutationsFactor binding sitesSchizophrenia casesSchizophrenia risk genesSomatic mosaicismSomatic variantsRisk genesG mutationGene expressionGermline mutationsBinding sitesGenesMutationsIncreased somatic mutationsChromatinMosaic somatic mutationsPrenatal neurogenesisContext of schizophreniaBrain neuronsSchizophrenia brainVariantsAndrogen receptor-mediated pharmacogenomic expression quantitative trait loci: implications for breast cancer response to AR-targeting therapy
Gao H, Wei L, Indulkar S, Nguyen T, Liu D, Ho M, Zhang C, Li H, Weinshilboum R, Ingle J, Wang L. Androgen receptor-mediated pharmacogenomic expression quantitative trait loci: implications for breast cancer response to AR-targeting therapy. Breast Cancer Research 2024, 26: 111. PMID: 38965614, PMCID: PMC11225427, DOI: 10.1186/s13058-024-01861-2.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalBenzamidesBreast NeoplasmsCell Line, TumorDihydrotestosteroneFemaleGene Expression Regulation, NeoplasticGenome-Wide Association StudyGenotypeHumansNitrilesPharmacogeneticsPharmacogenomic VariantsPhenylthiohydantoinPolymorphism, Single NucleotideQuantitative Trait LociReceptors, AndrogenConceptsSingle nucleotide polymorphismsGenome-wide associationDependent gene expressionSNP-gene pairsAromatase inhibitorsGenome-wide studiesAndrogen receptorBreast cancerSex hormone binding globulin levelsAR agonistsEffects of aromatase inhibitorsTop lociEffects of endocrine therapyAssociated with cancer riskMinor allele genotypeAR-targeted drugsAR-targeted therapiesTreatment of breast cancerGenotype-dependent mannerBreast cancer phenotypeNucleotide polymorphismsCell line panelEstrogen receptor aBreast cancer patientsGene expression
2022
Pharmacological targeting of androgen receptor elicits context-specific effects in estrogen receptor-positive breast cancer
Wei L, Gao H, Yu J, Zhang H, Nguyen T, Gu Y, Passow M, Carter J, Qin B, Boughey J, Goetz M, Weinshilboum R, Ingle J, Wang L. Pharmacological targeting of androgen receptor elicits context-specific effects in estrogen receptor-positive breast cancer. Cancer Research 2022, 83: 456-470. PMID: 36469363, PMCID: PMC9896025, DOI: 10.1158/0008-5472.can-22-1016.Peer-Reviewed Original ResearchConceptsER+ breast cancerAR-targeted therapiesBreast cancer modelAndrogen receptorBreast cancerAR agonistsCancer modelsAR/ER ratioEstrogen receptor-positive breast cancerReceptor-positive breast cancerAssociated with improved prognosisAR-targeted drugsAlterations of global gene expressionRelationship of ARBinding of ARER+ tumorsAR expressionCell growth inhibitionAR signalingImprove prognosisEstrogen receptorER levelsTumor growthTreatment strategiesEnz treatmentProteomic Biomarkers of Sacubitril/Valsartan Treatment Response in Heart Failure With Preserved Ejection Fraction: Molecular Insights Into Sex Differences
Nguyen T, Wang M, Liu D, Iyer S, Bonilla H, Acker N, Murthy V, Shrivastava S, Desai V, Burnett J, Redfield M, Bailey K, Weinshilboum R, Pereira N. Proteomic Biomarkers of Sacubitril/Valsartan Treatment Response in Heart Failure With Preserved Ejection Fraction: Molecular Insights Into Sex Differences. Circulation Heart Failure 2022, 15: e009629. PMID: 35656806, PMCID: PMC9489635, DOI: 10.1161/circheartfailure.122.009629.Peer-Reviewed Original Research
2020
Mood‐Stabilizing Antiepileptic Treatment Response in Bipolar Disorder: A Genome‐Wide Association Study
Ho A, Coombes B, Nguyen T, Liu D, McElroy S, Singh B, Nassan M, Colby C, Larrabee B, Weinshilboum R, Frye M, Biernacka J. Mood‐Stabilizing Antiepileptic Treatment Response in Bipolar Disorder: A Genome‐Wide Association Study. Clinical Pharmacology & Therapeutics 2020, 108: 1233-1242. PMID: 32627186, PMCID: PMC7669647, DOI: 10.1002/cpt.1982.Peer-Reviewed Original ResearchMeSH KeywordsAdultAffectAnticonvulsantsAntimanic AgentsBipolar DisorderFemaleGastrointestinal AbsorptionGenome-Wide Association StudyHumansLamotrigineMaleMiddle AgedMultidrug Resistance-Associated ProteinsOxcarbazepinePharmacogeneticsPharmacogenomic VariantsPolymorphism, Single NucleotideQuantitative Trait LociRetrospective StudiesThrombospondinsTreatment OutcomeValproic AcidConceptsSignificant single-nucleotide polymorphismsGenome-wide association studiesSplicing quantitative trait lociDiscovery genome-wide association studyGenome-wide significant single-nucleotide polymorphismsFood and Drug AdministrationGene-level associationsQuantitative trait lociBipolar disorderSingle-nucleotide polymorphismsBD patientsMood stabilizersTreatment responseGenetic lociTrait lociAssociation studiesHuman gutPharmacogenomic studiesMayo Clinic Bipolar Disorder BiobankUS Food and Drug AdministrationEvidence of associationAssociated with riskGenetic polymorphismsSLC35F3Clinical improvement
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