Enteroendocrine Regulation of Intestinal Metabolism
肠道代谢的肠内分泌调节
基本信息
- 批准号:10816027
- 负责人:
- 金额:$ 15.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:5&apos-AMP-activated protein kinaseAffectBiochemistryBiological AssayBiological ModelsBrainCarbon DioxideCell CommunicationCell LineCellsCommunitiesCommunity PhysicianCoupledDataDevelopmentDevelopmental BiologyDiarrheaDietary intakeDigestionDigestive System DisordersDistressElectrophysiology (science)EndocrinologyEnsureEnterocytesEnteroendocrine CellEnvironmentEpithelial CellsEpitheliumExhibitsFRAP1 geneFluorescenceG-Protein-Coupled ReceptorsGastroenterologyGenetic TranscriptionGenus HippocampusGoalsHealthHomeHormonesHumanHungerImageIndividualIngestionInstitutionInternationalIntestinesIonsLinkMass Spectrum AnalysisMeasuresMedical centerMedicineMentorsMetabolicMetabolic DiseasesMetabolismMitochondriaMusMutationNational Institute of Diabetes and Digestive and Kidney DiseasesNauseaNon-Insulin-Dependent Diabetes MellitusNutrientNutrient availabilityOrganOrganoidsPancreasPaneth CellsParenteral NutritionPathway interactionsPatientsPediatric HospitalsPediatric ResearchPeptide Signal SequencesPeptidesPhysiologyPlayPluripotent Stem CellsProductionProliferatingPublic HealthReceptor CellRegenerative capacityRegulationReporterResearchResearch PersonnelRespirationRoleSatiationScheduleScientistSecond Messenger SystemsSignal TransductionSmall IntestinesSystemTestingTimeTissuesTrainingUnited StatesUnited States National Institutes of HealthVomitingWorkblood glucose regulationcell motilitycell typedetection of nutrientdietaryexperimental studygastrointestinalgut healthhormonal signalshuman modelinnovationinsulin secretionintestinal epitheliumintestinal homeostasislarge scale productionmetabolic ratemetabolomicsmouse modelnovelnovel therapeuticsnutrient absorptionnutritionparacrinepharmacologicresponsesingle cell analysissingle-cell RNA sequencingstem cell functionstem cell nichestem cellssuccesstraining opportunitytranscription factoruptake
项目摘要
PROJECT SUMMARY
Dr. Heather McCauley is mentored by Dr. James Wells at Cincinnati Children’s Hospital Medical
Center (CCHMC), the largest pediatric research institution in the nation. CCHMC ranked 2nd in NIH support in
2017 and is home to an NIDDK-sponsored Digestive Diseases Research Center with a vibrant community of
physicians and scientists. CCHMC provides a very supportive training environment for young investigators. Dr.
McCauley proposes an innovative cross-disciplinary research plan which bridges developmental biology, stem
cell and organoid medicine, gastroenterology and nutrition, endocrinology, and metabolism.
Enteroendocrine cells (EECs) are specialized intestinal epithelial cells which secrete more than 20
bioactive peptides to regulate satiety, gut motility, glucose homeostasis, nutrient absorption, and whole-body
metabolism in response to ingested nutrients. While the systemic targets of EEC hormones are well known,
such as the brain and the pancreas, the role of EEC peptides in regulating the function of the intestine itself is
surprisingly understudied. Our lab has developed a unique, high-throughput human model system to test the
roles of individual EEC peptides on intestinal function by generating EEC-deficient human intestinal organoids
from pluripotent stem cells. We recently used this model system to show that some EECs regulate ion-coupled
nutrient absorption in neighboring cells. Because EECs are nutrient-sensing cells, we considered that they
might coordinate other intestinal responses to nutrient availability. Most EEC peptides signal via G-protein
coupled receptors which activate second messengers to modulate the function of their target cell. These
second messengers are intimately linked to ancient regulators of cellular metabolism, such as mammalian
target of rapamycin (mTOR), which are known to play essential roles in many intestinal functions. This
proposal will test the hypothesis that EECs regulate cellular metabolism in the stem cell niche (Aim 1) and in
the differentiated enterocyte (Aim 2), thus impacting both intestinal homeostasis and efficiency of nutrient
absorption. As EECs are now common targets for the treatment of type 2 diabetes, understanding how EECs
affect intestinal metabolism and function will inform how dietary or pharmacological manipulation of EECs will
impact gut health, nutrient absorption, and whole-body metabolism.
To ensure success of the proposed research strategy, Dr. McCauley requires additional mentored time
to become fluent in metabolic and metabolomic assays. Dr. McCauley has obtained a co-mentor, Dr. Kenneth
Setchell, an international expert in using Mass Spectrometry to understand nutrition- and digestive disease-
related changes in metabolism. Dr. McCauley proposes a rigorous yet feasible schedule of formal and informal
training opportunities in metabolomics. At the conclusion of the mentored portion of her training, Dr. McCauley
will be established as a fully independent, leading young investigator in the field of gastrointestinal metabolism,
a critically understudied niche in the GI community.
项目总结
项目成果
期刊论文数量(0)
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Heather A McCauley其他文献
Heather A McCauley的其他文献
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{{ truncateString('Heather A McCauley', 18)}}的其他基金
Enteroendocrine Regulation of Intestinal Metabolism
肠道代谢的肠内分泌调节
- 批准号:
10301046 - 财政年份:2021
- 资助金额:
$ 15.85万 - 项目类别:
Enteroendocrine Regulation of Intestinal Metabolism
肠道代谢的肠内分泌调节
- 批准号:
10475157 - 财政年份:2021
- 资助金额:
$ 15.85万 - 项目类别:
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