Thanh Thanh L. Nguyen, PhD
Postdoctoral FellowCards
About
Research
Overview
Public Health Interests
Genetics, Genomics, Epigenetics
Publications
Featured Publications
Glucocorticoids unmask silent non-coding genetic risk variants for common diseases
Nguyen T, Gao H, Liu D, Philips T, Ye Z, Lee J, Shi G, Copenhaver K, Zhang L, Wei L, Yu J, Zhang H, Barath A, Luong M, Zhang C, Gaspar-Maia A, Li H, Wang L, Ordog T, Weinshilboum R. Glucocorticoids unmask silent non-coding genetic risk variants for common diseases. Nucleic Acids Research 2022, 50: 11635-11653. PMID: 36399508, PMCID: PMC9723631, DOI: 10.1093/nar/gkac1045.Peer-Reviewed Original ResearchConceptsGene expressionGenomic sequence variantsNon-coding variantsCis-regulatory elementsLigand-dependent associationBreast cancer risk genesInfluence gene expressionCancer risk genesGenetic risk variantsGene-by-environment interactionsEpigenomic approachesSequence variantsAffected genesRisk variantsAssociated with clinical phenotypesRisk genesVariant functionDisease phenotypeDrug responseGenesDisease riskMechanistic frameworkMAST4Clinical phenotypeRisk factorsGlucocorticoids mediate transcriptome‐wide alternative polyadenylation: Potential mechanistic and clinical implications
Nguyen T, Liu D, Gao H, Ye Z, Lee J, Wei L, Yu J, Zhang L, Wang L, Ordog T, Weinshilboum R. Glucocorticoids mediate transcriptome‐wide alternative polyadenylation: Potential mechanistic and clinical implications. Clinical And Translational Science 2022, 15: 2758-2771. PMID: 36128656, PMCID: PMC9652440, DOI: 10.1111/cts.13402.Peer-Reviewed Original ResearchConceptsAlternative polyadenylationTranscriptome-wide alternative polyadenylationAssociated with multiple biological processesRegulating alternative polyadenylationGenetic regulatory mechanismsRNA-binding proteinsTranslation-related pathwaysGlucocorticoid-mediated expressionInvestigated transcriptome-wideMultiple biological processesCell type-specificHuman B lymphoblastoid cell lineTranscriptome-widePotential functional mechanismsRNA transcriptsGenetic variantsB-lymphoblastoid cell linesGene expressionRegulatory mechanismsBiological processesAntiviral inhibitorsImpact of glucocorticoidsDisease phenotypeGenesFunctional consequencesTCF7L2 lncRNA: a link between bipolar disorder and body mass index through glucocorticoid signaling
Liu D, Nguyen T, Gao H, Huang H, Kim D, Sharp B, Ye Z, Lee J, Coombes B, Ordog T, Wang L, Biernacka J, Frye M, Weinshilboum R. TCF7L2 lncRNA: a link between bipolar disorder and body mass index through glucocorticoid signaling. Molecular Psychiatry 2021, 26: 7454-7464. PMID: 34535768, PMCID: PMC8872993, DOI: 10.1038/s41380-021-01274-z.Peer-Reviewed Original ResearchConceptsSignificant single-nucleotide polymorphismsGenome-wide association studiesFunction of TCF7L2Expression quantitative trait lociGenome-wide significant single-nucleotide polymorphismsChromatin immunoprecipitation sequencingQuantitative trait lociNon-coding transcriptsBD risk genesRNA sequencing dataSingle-nucleotide polymorphismsGlucocorticoid-dependent repressionChIP-seqSequence dataTrait lociAssociation studiesParental genesMolecular functionsNon-coding RNAsTranscription factor 7Transcript variantsRisk genesInsulin signalingTCF7L2 knockdownLong non-coding RNAsAPOE4 exacerbates synapse loss and neurodegeneration in Alzheimer's disease patient iPSC-derived cerebral organoids.
Zhao J, Fu Y, Yamazaki Y, Ren Y, Davis MD, Liu CC, Lu W, Wang X, Chen K, Cherukuri Y, Jia L, Martens YA, Job L, Shue F, Nguyen TT, Younkin SG, Graff-Radford NR, Wszolek ZK, Brafman DA, Asmann YW, Ertekin-Taner N, Kanekiyo T, Bu G. APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer's disease patient iPSC-derived cerebral organoids. Nat Commun 2020, 11: 5540. PMID: 33139712, DOI: 10.1038/s41467-020-19264-0.Peer-Reviewed Original Research
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
2023
Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis
Liu D, Wang M, Murthy V, McNamara D, Nguyen T, Philips T, Vyas H, Gao H, Sahni J, Starling R, Cooper L, Skime M, Batzler A, Jenkins G, Barlera S, Pileggi S, Mestroni L, Merlo M, Sinagra G, Pinet F, Krejčí J, Chaloupka A, Miller J, de Groote P, Tschumperlin D, Weinshilboum R, Pereira N. Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis. Circulation Research 2023, 133: 810-825. PMID: 37800334, PMCID: PMC10746262, DOI: 10.1161/circresaha.123.323200.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesRecent-onset dilated cardiomyopathyGenome-wide association study signalsLeft ventricular ejection fractionVentricular ejection fractionDilated cardiomyopathyHuman cardiac fibroblastsCardiac fibrosisMyocardial recoveryEjection fractionHeart failureAssociated with improved cardiac functionTranscriptome profilingCDCP1 expressionStandard drug therapyMolecular mechanismsVariant allelesAttenuated cardiac fibrosisHeart failure patientsCellular modelKnockdownDecreased AktStudy signalsCDCP1
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