Dysregulation of Epithelial Metabolism and Regeneration by Sulfite Exposure in Pediatric Ulcerative Colitis
小儿溃疡性结肠炎亚硫酸盐暴露导致上皮代谢和再生失调
基本信息
- 批准号:10722914
- 负责人:
- 金额:$ 9.15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-01 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:Adverse effectsAffectAmericanAnimal ModelAwardBar CodesBiologyBiopsyCell Differentiation processCell RespirationCellsCellular Metabolic ProcessChildChild NutritionChildhoodChromatinColitisColonColonic inflammationComplexConsumptionDataDefectDeveloped CountriesDietDietary FactorsDigestive System DisordersDiseaseDisease ManagementDisease modelDrug Metabolic DetoxicationEnvironmentEnvironmental Risk FactorEpitheliumExcisionExposure toFood PreservativesFoundationsFundingFutureGenesGoalsHealthHomeostasisHumanImpairmentIncidenceInflammatory Bowel DiseasesIngestionIntakeIntestinesMaintenanceMetabolicMetabolismMitochondriaMitochondrial DNAModelingMusMutationNatural regenerationOrganoidsOutcomePathway interactionsPatientsPediatric ulcerative colitisPhasePhenotypePhysiologicalPlayPredispositionPrevalencePublishingRecoveryResearchResearch PersonnelRoleSafetySamplingScienceShapesSignal TransductionSiteSourceSulfitesSulfurTissuesTrainingUlcerative ColitisUnited States National Institutes of HealthVariantWorkbiobankcareerdietarydisorder controlepigenomeepigenomicsepithelial injuryepithelial repairepithelial stem cellfeedinggastrointestinal epitheliumgut microbiotahuman tissuein vivoinhibitorinnovationintestinal barrierintestinal epitheliummitochondrial DNA mutationmitochondrial dysfunctionmitochondrial metabolismmolybdenum cofactormouse modelnutritionpediatric patientsprogramsregenerativeresponseself-renewalskillsstem cell derived tissuesstem cell differentiationstem cellstranscriptomicswestern diet
项目摘要
PROJECT SUMMARY
The prevalence of ulcerative colitis (UC) in children continues to increase yearly. Recent evidence in pediatric
UC patients showed significant mitochondrial impairment in the colon tissues. This is important as optimal
mitochondrial activity is required for the solemn function of colonic stem cells that replenish the physical barrier
of the colon epithelium. Since patients are constantly exposed to environmental factors such as diet, it is critical
to reveal the dietary factors that influence mitochondrial function in the colon epithelium as they would be vital in
the management of UC in children. Sulfites are endogenous products of several sulfur-containing compounds,
and they are also ubiquitous in our diets as preservatives. My preliminary data in colon organoids derived from
pediatric patients showed a detrimental role of sulfite on mitochondrial metabolism and differentiation, with worse
metabolic outcomes in samples from pediatric UC patients. My analysis of transcriptomic data from 206 children
with UC showed that the Mocs1 gene required for downstream clearance of sulfites in the mitochondria is
downregulated in the colon of UC patients, suggesting a potential for inefficient sulfite detoxification in the colon.
In this study, I will use patient-derived colon organoids to define how sulfites regulate mitochondrial metabolism
and differentiation in health and in UC (Aim 1), reveal the sulfite-induced and sulfite susceptibility chromatin sites
in the pediatric colon that explains these metabolic and differentiation anomalies (Aim 2), and how sulfites and
the loss of epithelial Mocs1 shape colon biology in the complex gut environment in vivo using physiological
relevant models (Aim 3). This award will advance my training in disease models of IBD, epithelial biology, and
epigenomics as I work toward establishing an innovative career in regenerative nutrition with a focus on pediatric
digestive diseases and continue efforts to enhance diverse representation in the biomedical sciences.
项目概要
儿童溃疡性结肠炎(UC)的患病率逐年增加。儿科的最新证据
UC患者在结肠组织中表现出明显的线粒体损伤。这很重要,因为它是最佳的
线粒体活性是结肠干细胞补充物理屏障的重要功能所必需的
结肠上皮。由于患者不断暴露于饮食等环境因素,因此至关重要
揭示影响结肠上皮线粒体功能的饮食因素,因为它们对于
儿童 UC 的管理。亚硫酸盐是几种含硫化合物的内源产物,
它们作为防腐剂在我们的饮食中也无处不在。我的结肠类器官初步数据来自
儿科患者表现出亚硫酸盐对线粒体代谢和分化有不利作用,情况更糟
儿科 UC 患者样本的代谢结果。我对 206 名儿童的转录组数据的分析
与 UC 的研究表明,线粒体中亚硫酸盐下游清除所需的 Mocs1 基因是
在 UC 患者的结肠中下调,表明结肠中亚硫酸盐解毒的效率可能较低。
在这项研究中,我将使用患者来源的结肠类器官来定义亚硫酸盐如何调节线粒体代谢
以及健康和 UC 中的分化(目标 1),揭示亚硫酸盐诱导的染色质位点和亚硫酸盐易感性染色质位点
在儿科结肠中解释这些代谢和分化异常(目标 2),以及亚硫酸盐和
使用生理学方法在体内复杂的肠道环境中上皮 Mocs1 形状结肠生物学的丧失
相关模型(目标 3)。该奖项将促进我在 IBD 疾病模型、上皮生物学和
表观基因组学,我致力于在再生营养领域建立创新的职业生涯,重点关注儿科
消化系统疾病,并继续努力增强生物医学科学的多元化代表性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Babajide Ojo其他文献
Babajide Ojo的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 9.15万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 9.15万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 9.15万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 9.15万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 9.15万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 9.15万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 9.15万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 9.15万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 9.15万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 9.15万 - 项目类别:
Studentship














{{item.name}}会员




