Thanh Thanh L. Nguyen, PhD
Postdoctoral FellowCards
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Postdoctoral Fellow
Biography
I am a functional genomicist interested in elucidating genetic drivers of disease and translating findings into new diagnostics and targeted treatments. My PhD thesis integrated transcriptomic, genomic and epigenomic approaches to characterize environment-dependent genetic risk variants across autoimmunity, metabolism, mood disorders, osteoporosis and cancer (Nucleic Acids Research 2022, Molecular Psychiatry 2021). Currently as a co-mentored computational and experimental biologist, I am leveraging state-of-the-art massively parallel reporter assays, CRISPR screens and human stem cell technologies to (1) explore the genetic architecture driving functional variation of all human trait-associated genetic variants in the UK Biobank (Nature, under review), and (2) functionally characterize all brain non-coding somatic mosaic variants discovered to date, resolving their causal roles in schizophrenia (Science 2024).
Departments & Organizations
- All Institutions
Education & Training
- PhD
- Mayo Clinic, Molecular Pharmacology (2022)
- BA
- Green Mountain College, Self-design in Biology, Math & Philosophy (2017)
Research
Overview
Public Health Interests
ORCID
0000-0002-2281-6540- View Lab Website
Brennand Lab; Reilly Lab
Research at a Glance
Publications Timeline
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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGene 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 ResearchAltmetricMeSH Keywords and ConceptsConceptsAlternative 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsSignificant 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
Androgen 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 Keywords and ConceptsMeSH 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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGenome-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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsER+ 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 ResearchCitationsAltmetricMeSH Keywords and Concepts
2021
Mood Regulatory Actions of Active and Sham Nucleus Accumbens Deep Brain Stimulation in Antidepressant Resistant Rats
Kale R, Nguyen T, Price J, Yates N, Walder K, Berk M, Sillitoe R, Kouzani A, Tye S. Mood Regulatory Actions of Active and Sham Nucleus Accumbens Deep Brain Stimulation in Antidepressant Resistant Rats. Frontiers In Human Neuroscience 2021, 15: 644921. PMID: 34349629, PMCID: PMC8326323, DOI: 10.3389/fnhum.2021.644921.Peer-Reviewed Original ResearchConceptsNAc deep brain stimulationAntidepressant-like effectsNucleus accumbensInfralimbic cortexDeep brain stimulationMood networkForced swimming behavioral testsActive deep brain stimulationNucleus accumbens deep brain stimulationImmobility-reducing effectForced swimming immobility timeAntidepressant-like actionForced swim testTricyclic antidepressant treatmentEffect of imipramineOpen field testSwimming behavior testSwimming immobility timeBrain stimulationHome cage monitoringAction of deep brain stimulationMammalian target of rapamycinPost-mortem levelsProgressive neuroadaptationsAntidepressant resistanceSelective Serotonin Reuptake Inhibitor Pharmaco-Omics: Mechanisms and Prediction
Nguyen T, Liu D, Ho M, Athreya A, Weinshilboum R. Selective Serotonin Reuptake Inhibitor Pharmaco-Omics: Mechanisms and Prediction. Frontiers In Pharmacology 2021, 11: 614048. PMID: 33510640, PMCID: PMC7836019, DOI: 10.3389/fphar.2020.614048.Peer-Reviewed Original ResearchCitationsAltmetricConceptsMajor depressive disorderSignificant single nucleotide polymorphismsAlcohol use disorderGenome-wide association studiesFunctional genomic studiesSSRI therapyDecreased 5-HT concentrationsMajor depressive disorder patientsMDD symptom severitySerotonin reuptake inhibitorsGenomic studiesClathrin-mediated vesicle formationGenes associated with variationEthanol-responsive genesGenome-wide significant single nucleotide polymorphismsPlasma kynurenine levelsMDD trialsClinical responseDepressive disorderPGRN-AMPSReuptake inhibitorsUse disorderNeuropsychiatric disordersSymptom severitySSRIs
Academic Achievements & Community Involvement
honor Reviewer’s Choice Abstract (top 10%)
National AwardAmerican Society of Human GeneticsDetails10/01/2022honor Presidential Trainee Award
National AwardAmerican Society for Clinical Pharmacology & TherapeuticsDetails03/01/2022, 03/01/2021