grant
The Role of Tcf7l2 in maintaining liver zonation and metabolic homeostasis
Organization BOSTON CHILDREN'S HOSPITALLocation BOSTON, UNITED STATESPosted 1 Feb 2023Deadline 31 Jan 2028
NIHUS FederalResearch GrantFY2026AcuteAdult-Onset Diabetes MellitusAmino AcidsAnatomic SitesAnatomic structuresAnatomyAntidiabetic HormoneAntimorphic mutationAutoregulationBasal Transcription FactorBasal transcription factor genesBile AcidsBindingCell Communication and SignalingCell NucleusCell SignalingCentral VeinChIP SequencingChIP-seqChIPseqChromatinD-GlucoseDataDextroseDiabetes MellitusDiathesisDiseaseDisease susceptibilityDisorderDominant NegativeDominant-Negative MutantDominant-Negative MutationExpression SignatureFastingGene ExpressionGene Expression ProfileGene TranscriptionGeneral Transcription Factor GeneGeneral Transcription FactorsGenesGenetic TranscriptionGenetic studyGenotypeGlucagonGluconeogenesisGlucoseGlukagonGlycolysisGoalsHG-FactorHIF 1 alphaHIF-1alphaHIF1-AlphaHIF1AHIF1A geneHIF1αHNF4HNF4-AlphaHNF4AHNF4A geneHepaticHepatic CellsHepatic Parenchymal CellHepatocyteHepatocyte Nuclear Factor 4-AlphaHepatocyte Nuclear Factor, 4HeterogeneityHomeostasisHuman GeneticsHumulin RHyperglycemiaHyperglycemic-Glycogenolytic FactorIn VitroInsulinIntermediary MetabolismIntracellular Communication and SignalingKO miceKetosis-Resistant Diabetes MellitusKnock-outKnock-out MiceKnockoutKnockout MiceLipidsLiverLiver CellsLobuleLocationMOP1Maturity-Onset Diabetes MellitusMetabolicMetabolic ProcessesMetabolismMiceMice MammalsModelingMolecular InteractionMorphologyMurineMusNAFLDNIDDMNon-Insulin Dependent DiabetesNon-Insulin-Dependent Diabetes MellitusNoninsulin Dependent DiabetesNoninsulin Dependent Diabetes MellitusNovolin RNucleusNull MouseOvernutritionPathogenesisPatternPhysiologicPhysiologicalPhysiological HomeostasisPortal VeinPortal vein structurePredispositionProcessRNA ExpressionRegular InsulinRoleSignal TransductionSignal Transduction SystemsSignalingSingle-Nucleus SequencingSlow-Onset Diabetes MellitusStable Diabetes MellitusStressSusceptibilityT cell factor 4T cell transcription factor 4T-Cell-Specific Transcription Factor 4T2 DMT2DT2DMTCF-4TCF14TCF4TCF7L2TCF7L2 geneTcf4 transcription factorTcf712 transcription factorTechnologyTestingTranscriptTranscriptionTranscription Factor 14, Hepatic Nuclear FactorTranscription Factor 7-Like 2Transcription Factor Proto-OncogeneTranscription factor genesType 2 Diabetes MellitusType 2 diabetesType II Diabetes MellitusType II diabetesadult onset diabetesamino acid metabolismaminoacidbile acid metabolismbile metabolismbiological signal transductionchromatin immunoprecipitation coupled with sequencingchromatin immunoprecipitation followed by sequencingchromatin immunoprecipitation with sequencingchromatin immunoprecipitation-seqchromatin immunoprecipitation-sequencingdiabetesdiabeticdietaryfastedfastsfat metabolismfeedingforginggene expression patterngene expression signaturegenetic associationglucose biosynthesisglucose metabolismhepatic body systemhepatic organ systemhepatocyte injuryhuman diseasehyperglucagonemiahyperglycemicindividualized strategiesinsightketosis resistant diabetesliability to diseaselipid metabolismmaturity onset diabetesmetabolism measurementmetabolomicsmetabonomicsmouse modelmurine modelnon-alcohol fatty liver diseasenon-alcoholic fatty liver diseasenon-alcoholic liver diseasenonalcoholic fatty liver diseasenovelpersonalized strategiespreventpreventingprogramsresponsesNuc-Seqsingle nucleus RNA-sequencingsingle nucleus seqsingle-nucleus RNA-seqsnRNA sequencingsnRNA-seqsocial roletooltranscription factortranscriptional profiletranscriptional signaturetype 2 DMtype II DMtype two diabetesurea cyclewestern dietwestern-style dietwestern-type diet
Description preview
Abstract
Fifteen years ago, genetic studies identified an association between TCF7L2 and diabetes; more recently an
association with non-alcoholic fatty liver disease (NAFLD) was identified. Yet, the role of TCF7L2, particularly
in the liver, remains controversial. We think that progress to date has been hindered by (1) use of dominant
negative…
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