Thanh Thanh L. Nguyen, PhD
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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) and autism spectrum disorder.
Since joining Yale I have mentored eight trainees from diverse nationalities and backgrounds, and supervised a masters thesis and an undergraduate senior thesis (Boell Prize Award 2025).
Last Updated on May 31, 2025.
Education & Training
- PhD
- Mayo Clinic, Molecular Pharmacology (2022)
- BA
- Green Mountain College, Self-design in Biology, Math & Philosophy (2017)
Research
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Overview
Public Health Interests
Genetics, Genomics, Epigenetics
ORCID
0000-0002-2281-6540- View Lab Website
Brennand Lab; Reilly Lab
Research at a Glance
Yale Co-Authors
Frequent collaborators of Thanh Thanh L. Nguyen's published research.
Publications Timeline
A big-picture view of Thanh Thanh L. Nguyen's research output by year.
Steven Reilly, PhD
Abhijeet Singh Barath, MBBS, PhD
Alexej Abyzov, PhD
Kristen Brennand, PhD
19Publications
636Citations
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 factorsMachine-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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCis-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 ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsTranscription 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 brainVariants
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 ResearchCitationsMeSH 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 treatmentGlucocorticoids 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 consequencesProteomic 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 ConceptsSACUBITRIL/VALSARTAN PROTEOMIC BIOMARKERS FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION: MOLECULAR INSIGHTS ASSOCIATED WITH SEX DIFFERENCES IN DRUG RESPONSE
Nguyen T, Wang M, Liu D, Iyer S, Acker N, Bonilla H, Murthy V, Shrivastava S, Desai V, Burnett J, Redfield M, Weinshilboum R, Pereira N. SACUBITRIL/VALSARTAN PROTEOMIC BIOMARKERS FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION: MOLECULAR INSIGHTS ASSOCIATED WITH SEX DIFFERENCES IN DRUG RESPONSE. Journal Of The American College Of Cardiology 2022, 79: 297. DOI: 10.1016/s0735-1097(22)01288-8.Peer-Reviewed Original ResearchCitationsAltmetric
2021
TCF7L2 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 RNAs
Academic Achievements & Community Involvement
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Honors
honor Keystone Scholarship
02/24/2025International AwardKeystone SymposiaDetailsUnited Stateshonor Reviewer’s Choice Abstract (top 10%)
10/01/2022National AwardAmerican Society of Human Geneticshonor Presidential Trainee Award
03/01/2022, 03/01/2021National AwardAmerican Society for Clinical Pharmacology & Therapeutics
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