grant

NRF2-ACSS2 Axis in Alcohol-induced Metabolic Reprogramming and Esophageal Pathology

Organization CORIELL INSTITUTE FOR MEDICAL RESEARCHLocation CAMDEN, UNITED STATESPosted 1 Aug 2022Deadline 31 Jul 2027
NIHUS FederalResearch GrantFY2025Absolute ethanolAcetaldehydeAcetatesAcetyl CoAAcetyl Coenzyme AAcid RefluxAcid-Thiol LigasesAcyl CoA SynthetasesAcyl Coenzyme A SynthetasesAlcohol Chemical ClassAlcohol DrinkingAlcohol consumptionAlcoholsAnimal ModelAnimal Models and Related StudiesAssayAutoradiographyBasal Transcription FactorBasal transcription factor genesBioassayBiological AssayBody TissuesCancer Causing AgentsCancersCarbonCarcinogensCell BodyCell Communication and SignalingCell Growth in NumberCell MultiplicationCell ProliferationCell SignalingCell modelCellsCellular ProliferationCellular modelCitric Acid CycleClinicalCo A LigasesCoenzyme A LigasesCoenzyme A SynthetasesCultured CellsDNADataDeoxyribonucleic AcidDietDoseDrug Metabolic DetoxicationDrug Metabolic DetoxificationETOHEpithelial CellsEsophageal CancerEsophageal DiseasesEsophageal DisorderEsophageal Epidermoid CarcinomaEsophageal RefluxEsophageal SCCEsophageal Squamous CellEsophageal Squamous Cell CarcinomaEsophagusEsophagus CancerEtOH drinkingEtOH useEthanalEthanolEthanol MetabolismEthyl AlcoholFamily memberFoundationsFutureGERDGastro-oesophageal RefluxGastroesophageal RefluxGastroesophageal reflux diseaseGene ExpressionGene ModifiedGene TranscriptionGeneral Transcription Factor GeneGeneral Transcription FactorsGenesGenetic TranscriptionGenus HippocampusGrain AlcoholHistone AcetylationHumanHyperactivityIn VitroIntermediary MetabolismIntracellular Communication and SignalingIsocaloricKrebs CycleLabelLinkLipidsLiquid substanceMalignant CellMalignant Esophageal NeoplasmMalignant Esophageal TumorMalignant NeoplasmsMalignant TumorMalignant Tumor of the EsophagusMalignant neoplasm of esophagusMeasuresMediatingMembrane Transport ProteinsMembrane TransportersMetabolicMetabolic Drug DetoxicationsMetabolic ProcessesMetabolismMetabolism of Toxic AgentsMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic TumorMethylcarbinolMiceMice MammalsModelingModern ManMolecularMurineMusNF-E2 proteinNF-E2 transcription factorNFE2 proteinNeoplasm MetastasisOncogensPET/CTPET/CT scanPathologyPhasePhenotypePreventative measurePreventivePreventive measureProductionProteinsRNA ExpressionRadioautographyRegulationRisk FactorsRoleS-acetate Coenzyme ASCC of the EsophagusSeahorseSecondary NeoplasmSecondary TumorSignal TransductionSignal Transduction SystemsSignalingSolidSourceSquamous Cell Carcinoma of the EsophagusTCA cycleTestingTimeTissuesTranscriptionTranscription Factor Proto-OncogeneTranscription factor genesTranslatingTricarboxylic Acid CycleWorkadipogenesisalcohol exposedalcohol exposurealcohol ingestionalcohol intakealcohol metabolismalcohol preventionalcohol product usealcohol usealcoholic beverage consumptionalcoholic drink intakebiological signal transductioncancer cellcancer metastasiscancer progressiondensitydesigndesigningdetoxificationdietsdiseases of esophagusesophageal squamous epithelial cellesophagus disorderethanol consumptionethanol drinkingethanol exposedethanol exposureethanol ingestionethanol intakeethanol product useethanol useexposed to alcoholexposed to ethanolexposure to alcoholexposure to ethanolfluidgene modificationgenetically modifiedin vivoinhibitorknock-downknockdownlipid biosynthesislipogenesisliquidmalignancymetabolism measurementmetabolomicsmetabonomicsmodel of animalneoplasm progressionneoplasm/cancerneoplastic progressionnovelnuclear factor-erythroid 2oesophageal canceroncogenic agentpositron emission computed tomographysocial rolestable isotopethiokinasetranscription factortumor cell metastasistumor progressionuptake
Sign up free to applyApply link · pipeline · email alerts
— or —

Get email alerts for similar roles

Weekly digest · no password needed · unsubscribe any time

Full Description

PROJECT SUMMARY
This multiple-PI R01 proposal is designed to incorporate both in vitro and in vivo approaches to elucidate the
role of the NRF2-ACSS2 axis in alcohol-induced metabolic reprogramming and esophageal pathology. We
hypothesize that the NRF2-ACSS2 axis mediates metabolic reprogramming in alcohol-associated esophageal
pathology. We will test this hypothesis using human cells and genetically modified mice through three
independent and complementary Specific Aims. In Aim 1, we will characterize the role of NRF2-ACSS2 axis in
mediating alcohol-induced metabolic reprogramming in human esophageal squamous epithelial cells in vitro. In
Aim 2, we will validate the role of the NRF2-ACSS2 axis in mediating alcohol-induced metabolic
reprogramming in mouse esophagus in vivo. In Aim 3, we will examine the inhibitory effects of NRF2 and
ACSS2 inhibitors on alcohol-induced metabolic reprogramming and esophageal pathology in vivo. If the
hypothesis proved to be true, these studies will lay down a solid mechanistic foundation for NRF2/ACSS2
inhibition as a novel mechanism-based preventive measure against alcohol-associated esophageal pathology
in the future.

Grant Number: 5R01AA030026-05
NIH Institute/Center: NIH
Principal Investigator: XIAOXIN CHEN

Sign up free to get the apply link, save to pipeline, and set email alerts.

Sign up free →

Agency Plan

7-day free trial

Unlock procurement & grants

Upgrade to access active tenders from World Bank, UNDP, ADB and more — with email alerts and pipeline tracking.

$29.99 / month

  • 🔔Email alerts for new matching tenders
  • 🗂️Track tenders in your pipeline
  • 💰Filter by contract value
  • 📥Export results to CSV
  • 📌Save searches with one click
Start 7-day free trial →

Explore more

📍 More grants in UNITED STATES🏷 More NIH opportunities🏷 More US Federal opportunities🏷 More Research Grant opportunities🏢 All nih_reporter opportunities