Carson Thoreen, PhD
Associate Professor Term of Cellular & Molecular PhysiologyDownloadHi-Res Photo
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Cellular & Molecular Physiology
Primary
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About
Titles
Associate Professor Term of Cellular & Molecular Physiology
Appointments
Cellular & Molecular Physiology
Associate Professor on TermPrimary
Other Departments & Organizations
- Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS)
- Cellular & Molecular Physiology
- Center for RNA Science and Medicine
- Diabetes Research Center
- Molecular Medicine, Pharmacology, and Physiology
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
Education & Training
- PhD
- Massachusettes Institute of Technology (2008)
- ScB
- Brown University, Biology (2000)
Research
Overview
The mammalian target of rapamycin (mTOR) pathway is an evolutionarily conserved master regulator of cell growth with important roles in metabolism, aging and cancer. The pathway senses nutrient and growth signals, and responds to these by regulating many major metabolic pathways, but particularly mRNA translation. We found that acute inhibition of mTOR selectively inhibits the translation of large class of mRNAs containing a terminal oligopyrimidine (TOP) motif at the 5’ terminus by disrupting the mRNA cap-binding complex, eIF4F. The mTOR pathway has many additional targets in the translational machinery, but the functional significance of these is unknown. We want to understand how mTOR-regulated translational mechanisms work in molecular detail, what features in mRNAs determine their dependence on mTOR activity, and how these controls are employed physiologically.
Medical Research Interests
Biochemistry; Metabolism; Physiology; Translations
ORCID
0000-0003-1164-7224- View Lab Website
Thoreen Lab
Research at a Glance
Yale Co-Authors
Frequent collaborators of Carson Thoreen's published research.
Publications Timeline
A big-picture view of Carson Thoreen's research output by year.
Maegan Watson, PhD
14Publications
7,269Citations
Publications
2022
mRNA 5′ terminal sequences drive 200-fold differences in expression through effects on synthesis, translation and decay
van den Elzen A, Watson M, Thoreen C. mRNA 5′ terminal sequences drive 200-fold differences in expression through effects on synthesis, translation and decay. PLOS Genetics 2022, 18: e1010532. PMID: 36441824, PMCID: PMC9731452, DOI: 10.1371/journal.pgen.1010532.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsTerminal sequenceGene expressionKey post-transcriptional regulatorsTerminal oligopyrimidine motifsCore promoter motifsPost-transcriptional regulatorsPromoter motifsMRNA decayTranslation initiationRegulatory sequencesReporter mRNAEfficient transcriptionLibrary sequencesEndogenous mRNARegulatory potentialNative mRNAHuman cellsTranscriptionMRNAHybrid sequencesSequenceExpressionMotifMRNA expressionTranslation
2020
Roadblock-qPCR: a simple and inexpensive strategy for targeted measurements of mRNA stability
Watson M, Park Y, Thoreen C. Roadblock-qPCR: a simple and inexpensive strategy for targeted measurements of mRNA stability. RNA 2020, 27: 335-342. PMID: 33288682, PMCID: PMC7901842, DOI: 10.1261/rna.076885.120.Peer-Reviewed Original ResearchCitationsAltmetric
2017
La-related protein 1 (LARP1) repression of TOP mRNA translation is mediated through its cap-binding domain and controlled by an adjacent regulatory region
Philippe L, Vasseur JJ, Debart F, Thoreen CC. La-related protein 1 (LARP1) repression of TOP mRNA translation is mediated through its cap-binding domain and controlled by an adjacent regulatory region. Nucleic Acids Research 2017, 46: gkx1237-. PMID: 29244122, PMCID: PMC5814973, DOI: 10.1093/nar/gkx1237.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAutoantigensBase SequenceBinding SitesBinding, CompetitiveCell-Free SystemComputational BiologyEukaryotic Initiation Factor-4FGene Expression RegulationHEK293 CellsHumansMechanistic Target of Rapamycin Complex 1Models, GeneticPolyribosomesProtein BindingProtein BiosynthesisProtein Interaction Domains and MotifsPyrimidinesRibonucleoproteinsRNA, MessengerConceptsTOP mRNA translationAdjacent regulatory regionsMRNA translationCap-binding domainCap structureRegulatory regionsEukaryotic initiation factor 4FMRNA 5' cap structureIntrinsic repressive activityTerminal oligopyrimidine motifsInitiation factor 4FMRNA 5' endsC-terminal halfGrowth-related mRNAsTOP mRNAsRepressive activityTranslation factorsMRNA targetsCoordinated changesGene expressionLARP1Cell growthProtein 1Top sequenceMRNAmTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis through Post-transcriptional Control of ATF4
Park Y, Reyna-Neyra A, Philippe L, Thoreen CC. mTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis through Post-transcriptional Control of ATF4. Cell Reports 2017, 19: 1083-1090. PMID: 28494858, PMCID: PMC5811220, DOI: 10.1016/j.celrep.2017.04.042.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsUpstream open reading framesATF4 translationTranscriptional programsProtein synthesisEukaryotic initiation factor 2 alphaInitiation factor 2 alphaPost-transcriptional controlRapamycin complex 1Open reading frameIntegrated stress responseAmino acid transportersTranscription factor 4Translation machineryTranslation repressorProtein familyReading frameMaster regulatorPromoter elementsBioinformatics analysisResponsive mRNAsAmino acid supplyStress responseMetabolic enzymesKey effectorsAcid transportersmTORC1 balances cellular amino acid supply with demand for protein synthesis through post‐transcriptional control of ATF4
Thoreen C, Park Y. mTORC1 balances cellular amino acid supply with demand for protein synthesis through post‐transcriptional control of ATF4. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.614.32.Peer-Reviewed Original ResearchConceptsUpstream open reading framesATF4 translationTranscriptional programsProtein synthesisEukaryotic initiation factor 2 alphaInitiation factor 2 alphaPost-transcriptional controlRapamycin complex 1Open reading frameIntegrated stress responseAmino acid transportersTranscription factor 4Translation machineryTranslation repressorProtein familyReading frameMaster regulatorPromoter elementsBioinformatics analysisResponsive mRNAsAmino acid supplyStress responseMetabolic enzymesKey effectorsAcid transporters
2016
ERK and p38 MAPK Activities Determine Sensitivity to PI3K/mTOR Inhibition via Regulation of MYC and YAP
Muranen T, Selfors L, Hwang J, Gallegos L, Coloff J, Thoreen C, Kang S, Sabatini D, Mills G, Brugge J. ERK and p38 MAPK Activities Determine Sensitivity to PI3K/mTOR Inhibition via Regulation of MYC and YAP. Cancer Research 2016, 76: 7168-7180. PMID: 27913436, PMCID: PMC5161652, DOI: 10.1158/0008-5472.can-16-0155.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsBlotting, WesternCell Line, TumorCell ProliferationDrug Resistance, NeoplasmExtracellular Signal-Regulated MAP KinasesFemaleFluorescent Antibody TechniqueHeterograftsHumansMAP Kinase Signaling SystemMiceMice, Inbred NODMicroscopy, ConfocalNeoplasms, ExperimentalP38 Mitogen-Activated Protein KinasesPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsProtein Kinase InhibitorsProto-Oncogene MasProto-Oncogene Proteins c-mycSignal TransductionTOR Serine-Threonine KinasesTranscription FactorsYAP-Signaling ProteinsConceptsPI3K/mTOR inhibitorMTOR inhibitorsTumor cellsPI3K/mTOR pathwayCell-targeted therapiesTranscriptional regulator c-MycPI3K/mTORAnimal tumor modelsUpregulation of MYCChronic inhibitionInhibition of p38Cellular signaling mechanismsTumor growthMTOR pathwayTumor modelAberrant activationTherapyStress kinase p38C-MycKinase p38InhibitionConstitutive ERK activityAttractive targetContext-dependent mechanismsProliferation arrest
2012
A unifying model for mTORC1-mediated regulation of mRNA translation
Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 2012, 485: 109-113. PMID: 22552098, PMCID: PMC3347774, DOI: 10.1038/nature11083.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords5' Untranslated RegionsAnimalsBase SequenceCell Line, TumorEukaryotic Initiation Factor-4EEukaryotic Initiation Factor-4GGene Expression RegulationHumansMaleMechanistic Target of Rapamycin Complex 1MiceModels, BiologicalMultiprotein ComplexesNaphthyridinesNucleotide MotifsPhosphorylationProstatic NeoplasmsProtein BindingProtein BiosynthesisProteinsRibosomesRNA, MessengerTOR Serine-Threonine Kinases
2009
An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1*
Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS. An ATP-competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-resistant Functions of mTORC1*. Journal Of Biological Chemistry 2009, 284: 8023-8032. PMID: 19150980, PMCID: PMC2658096, DOI: 10.1074/jbc.m900301200.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAdaptor Proteins, Signal TransducingAdenosine TriphosphateAnimalsAntibiotics, AntineoplasticAutophagyCarrier ProteinsCell Cycle ProteinsCell ProliferationCell SurvivalCells, CulturedDrug Resistance, NeoplasmEukaryotic Initiation FactorsImmunosuppressive AgentsMechanistic Target of Rapamycin Complex 1MiceMice, KnockoutMultienzyme ComplexesMultiprotein ComplexesPhosphoproteinsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Protein BiosynthesisProteinsRNA CapsSirolimusTOR Serine-Threonine KinasesTranscription FactorsConceptsRapamycin-resistant phosphorylationATP-competitive mammalian targetMammalian targetATP-competitive mTOR inhibitorsCell growthCap-dependent translationImpairs cell growthSuppression of autophagyDistinct complexesRapamycin kinaseCatalytic subunitKinase activityMTORC1 inhibitorMTORC2 inhibitionRapamycinAnti-cancer agentsDirect inhibitorMTOR inhibitorsInhibitorsProliferationMTORC2Torin1KinaseComplexesPhosphorylation
2006
mSin1 Is Necessary for Akt/PKB Phosphorylation, and Its Isoforms Define Three Distinct mTORC2s
Frias M, Thoreen C, Jaffe J, Schroder W, Sculley T, Carr S, Sabatini D. mSin1 Is Necessary for Akt/PKB Phosphorylation, and Its Isoforms Define Three Distinct mTORC2s. Current Biology 2006, 16: 1865-1870. PMID: 16919458, DOI: 10.1016/j.cub.2006.08.001.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAkt/PKBSerine/threonine kinaseAkt/PKB phosphorylationDistinct multiprotein complexesAssembly of mTORC2Multiprotein complexesThreonine kinaseAlternative splicingPKB phosphorylationMTORC2PKBMammalian targetCell growthMSin1KinaseIsoformsImportant roleSplicingComplexesPhosphorylationRapamycinProteinDifferent signalsRegulationMetabolism
2004
Huntingtin aggregates ask to be eaten
Thoreen C, Sabatini D. Huntingtin aggregates ask to be eaten. Nature Genetics 2004, 36: 553-554. PMID: 15167929, DOI: 10.1038/ng0604-553.Peer-Reviewed Original ResearchCitations
News
News
- January 23, 2022Source: YaleNews
Yale Researchers Track the Lifespan and Myriad Functions of mRNA
- January 09, 2020
Cellular and Molecular Physiology Annual Retreat 2019
- December 06, 2018
Cellular and Molecular Physiology Annual Retreat 2018
- September 25, 2018
Faculty and trainees from across Connecticut assemble at the Yale Center for RNA Science and Medicine’s 7th Annual Retreat
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