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Mechanisms of fasting-induced radioprotection of small intestinal epithelial cells

Mechanisms of fasting-induced radioprotection of small intestinal epithelial cells
禁食诱导的小肠上皮细胞辐射防护机制
批准号：
10645872
负责人：
HELEN M PIWNICA-WORMS
金额：
$66.15万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
项目状态：
未结题
起止时间：
2023-06-01 至 2028-05-31
来源：
https://reporter.nih.gov/project-details/10645872
关键词：
3-hydroxy-3-methylglutaryl-coenzyme AAnimalsAutomobile DrivingBacteriaCancer PatientCell SeparationCellsChIP-seqChromatinClinicalCoenzyme ADataDoseEnhancersEpigenetic ProcessEpithelial CellsFastingGene ExpressionGenesGenetic TranscriptionGoalsHDAC4 geneHistone H3Histone H4IntestinesIonizing radiationKetone BodiesKnock-outLysineMalignant neoplasm of pancreasMediatingMetabolicMusNormal tissue morphologyOrganOutcomePatientsProbioticsProductionQuality of lifeRadiationRadiation Dose UnitRadiation ProtectionRadiation ToxicityRadiation induced damageRadiation therapyReactionRegimenResolutionSmall Intestinal Goblet CellSmall IntestinesTestingToxic effectbeta-Hydroxybutyratecell killingepigenomeepigenomicsexperimental studygastrointestinalgut microbiomeimprovedinsightintestinal cryptintestinal homeostasisketogenesismicrobialmicrobiome alterationmimeticsmouse modelneoplastic cellnovelpancreas radiation therapypreservationprogramspromoterprotective effectradioprotectedrepairedresponseside effectsingle cell analysisstem cellstranscriptome sequencing

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Project Summary We demonstrated that short-term fasting protects mice from high dose ionizing radiation by protecting small intestinal (SI) stem cells, thereby preserving SI homeostasis and promoting organismal survival. We also showed that the major ketone body produced by fasting directly modifies the epigenome of SI epithelial cells to induce gene expression changes and that fasting alters the gut microbiome to favor bacteria whose metabolites are known to induce epigenetic and gene expression changes. We will test the hypothesis that ketone bodies and microbial metabolites induced by fasting, cause epigenetic and gene expression changes in SI epithelial cells thereby providing GI radioprotection.
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会议论文
Fasting Protects Small Intestinal Stem Cells from Lethal DNA Damage: Mechanistic Insight and Preclinical Translation
Fasting Protects Small Intestinal Stem Cells from Lethal DNA Damage: Mechanistic Insight and Preclinical Translation
CHARACTERIZATION OF PROTEIN PHOSPHORYLATION OF HUMAN CHK2 PROTEIN KINASE
  • 批准号：
    8361353
  • 项目类别：
  • 资助金额：
    $1.08万
  • 财政年份：
    2011
  • 负责人：
    HELEN M PIWNICA-WORMS
  • 依托单位：
    WASHINGTON UNIVERSITY
CHARACTERIZATION OF PROTEIN PHOSPHORYLATION OF HUMAN CHK2 PROTEIN KINASE
  • 批准号：
    8168703
  • 项目类别：
  • 资助金额：
    $0.97万
  • 财政年份：
    2010
  • 负责人：
    HELEN M PIWNICA-WORMS
  • 依托单位：
    WASHINGTON UNIVERSITY
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