Non-invasive analysis of methylated cell free DNA in necrotizing enterocolitis
坏死性小肠结肠炎甲基化细胞游离 DNA 的无创分析
基本信息
- 批准号:10704229
- 负责人:
- 金额:$ 58.99万
- 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:2021-08-12 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:Abdominal RadiographyAffectAge of OnsetAirAntibioticsBiologicalBiological AssayBiological MarkersBiologyBloodBlood specimenCase/Control StudiesCell LineageChemicalsClinicalClinical DataComplicationDNADNA MethylationDNA Methylation InhibitionDataDetectionDevelopmentDiagnosisDiagnostic ProcedureDiseaseEarly DiagnosisEconomic BurdenEnterocytesEnvironmental Risk FactorEpigenetic ProcessExcisionFecesGastrointestinal DiseasesGeneticGenetic TranscriptionGrowthHematopoieticHypermethylationInfantInfectionInflammatory ResponseIntestinesLasersLeukocytesMapsMetadataMethodsMethylationMorbidity - disease rateNecrosisNecrotizing EnterocolitisNeonatalNon-Invasive DetectionOnset of illnessOperative Surgical ProceduresOrgan failurePathogenesisPathogenicityPathologicPathway interactionsPhenotypePredispositionPremature InfantPremature Infant DiseasesRegimenRegulationReproducibilityResectedResourcesRiskSamplingScreening procedureSpecimenTestingTimeUterusabdominal distensionbiobankbisulfite sequencingbody systemcell free DNAcourse developmentdiagnostic strategyepigenomeepigenomicsfeedinggenome-widegenomic datahigh riskhuman tissueimprovedinnovationinsightintestinal injuryliquid biopsymedication administrationmicrobiomemolecular phenotypemortalitymouse modelneonatal micenovelnovel markerpostnatal developmentprecision medicinepredictive toolsprematurepreventprognostic toolprospectivescreeningsingle-cell RNA sequencingstool sampletranscriptomicswhole genome
项目摘要
Project Summary/Abstract
Necrotizing enterocolitis (NEC) is a devastating complication of prematurity that develops suddenly and carries
significant morbidity and a high mortality rate for which no biomarkers exist. The high mortality rate seen in NEC
could likely be prevented if there was a screening method that permitted early disease detection. Predictive and
prognostic tools for NEC are essential to advance our biological insight with a view towards non-invasive
detection and accurate and timely phenotyping. We have developed a NEC Biorepository with a variety of
specimen types and extensive clinical metadata obtained prospectively from premature infants before the
development of NEC. These samples allow us to interrogate the mechanisms that underlie NEC development,
including genetic or environmental factors. These factors include epigenetic mechanisms that regulate important
aspects of cellular differentiation and gut development. Importantly, the epigenetic mechanisms, specifically, at
the level of DNA methylation that take place during neonatal NEC are unknown. Our preliminary epigenomic
data demonstrate that numerous biological pathways are altered during NEC. Based on these findings, we now
hypothesize that non-invasive identification of methylation signatures can identify an infant at risk for necrotizing
enterocolitis. We will test this hypothesis by defining and quantifying the DNA methylation signatures in stool and
blood of premature infants before, during and after the development of NEC. Moreover, we will expand on our
observations that dysregulation of multiple key pathways is a defining pathogenic feature of NEC and use our
mouse model to gain additional mechanistic insights into NEC pathobiology. By the conclusion of the proposal,
we will have generated a considerable amount of genomic data from infants across the time course of
development and manifestation of NEC, and also during the normal extrauterine development of preterm infants.
These studies will advance our understanding of the epigenomic regulation of the pathways involved during NEC
development, and furthermore, may explain the unique susceptibility of the premature infant to NEC and identify
a non-invasive approach to diagnosing this devastating disease.
项目总结/摘要
坏死性小肠结肠炎(NEC)是早产儿的一种毁灭性并发症,
显著的发病率和高死亡率,对此不存在生物标志物。NEC的高死亡率
如果有一种筛查方法可以早期发现疾病的话,预测和
NEC的预后工具对于推进我们对非侵入性的生物学见解至关重要
检测和准确及时的表型分型。我们开发了一个NEC生物储存库,
样本类型和广泛的临床元数据,
NEC的发展。这些样本使我们能够询问NEC发展的基础机制,
包括遗传或环境因素。这些因素包括表观遗传机制,调节重要的
细胞分化和肠道发育方面。重要的是,表观遗传机制,特别是,在
在新生儿NEC期间发生的DNA甲基化水平是未知的。我们初步的表观基因组
数据表明在NEC期间许多生物学途径被改变。基于这些发现,我们现在
假设甲基化标记非侵入性鉴定可以鉴定处于坏死风险中的婴儿
肠炎我们将通过定义和量化粪便中的DNA甲基化特征来测试这一假设,
在NEC发生之前、期间和之后,早产儿的血液。此外,我们将扩大我们的
观察到多个关键通路的失调是NEC的一个定义性致病特征,并使用我们的
小鼠模型,以获得对NEC病理生物学的额外机制见解。在提案结束时,
我们将从婴儿的整个时间过程中产生大量的基因组数据,
NEC的发展和表现,以及早产儿的正常子宫外发育期间。
这些研究将促进我们对NEC过程中所涉及的通路的表观基因组调控的理解。
此外,还可以解释早产儿对NEC的独特易感性,并确定
一种非侵入性的方法来诊断这种毁灭性的疾病。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Microfluidic Model of Necrotizing Enterocolitis Incorporating Human Neonatal Intestinal Enteroids and a Dysbiotic Microbiome.
结合人类新生儿肠肠类和失调微生物组的坏死性小肠结肠炎的微流体模型。
- DOI:10.3791/65605
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Frazer,LaurenC;Yamaguchi,Yukihiro;Jania,CoreyM;Lanik,WyattE;Gong,Qingqing;Singh,DhirendraK;Mackay,Stephen;Akopyants,NataliaS;Good,Misty
- 通讯作者:Good,Misty
Dilemmas in feeding infants with intestinal failure: a neonatologist's perspective.
- DOI:10.1038/s41372-022-01504-4
- 发表时间:2023-01
- 期刊:
- 影响因子:2.9
- 作者:Hair, Amy B.;Good, Misty
- 通讯作者:Good, Misty
Necrotizing enterocolitis: Bench to bedside approaches and advancing our understanding of disease pathogenesis.
坏死性小肠结肠炎:长凳到床边的方法,并促进我们对疾病发病机理的理解。
- DOI:10.3389/fped.2022.1107404
- 发表时间:2022
- 期刊:
- 影响因子:2.6
- 作者:
- 通讯作者:
Identification of serum biomarkers for necrotizing enterocolitis using aptamer-based proteomics.
- DOI:10.3389/fped.2023.1184940
- 发表时间:2023
- 期刊:
- 影响因子:2.6
- 作者:
- 通讯作者:
Dilemmas in human milk fortification.
- DOI:10.1038/s41372-022-01502-6
- 发表时间:2023-01
- 期刊:
- 影响因子:2.9
- 作者:Hair, Amy B.;Scottoline, Brian;Good, Misty
- 通讯作者:Good, Misty
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MISTY L GOOD其他文献
MISTY L GOOD的其他文献
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{{ truncateString('MISTY L GOOD', 18)}}的其他基金
Neonatal gut-on-a-chip platform for high content drug testing and precision medicine
用于高内涵药物测试和精准医学的新生儿肠道芯片平台
- 批准号:
10594705 - 财政年份:2022
- 资助金额:
$ 58.99万 - 项目类别:
Neonatal gut-on-a-chip platform for high content drug testing and precision medicine
用于高内涵药物测试和精准医学的新生儿肠道芯片平台
- 批准号:
10491072 - 财政年份:2022
- 资助金额:
$ 58.99万 - 项目类别:
Neonatal gut-on-a-chip platform for high content drug testing and precision medicine
用于高内涵药物测试和精准医学的新生儿肠道芯片平台
- 批准号:
10674890 - 财政年份:2022
- 资助金额:
$ 58.99万 - 项目类别:
Non-invasive analysis of methylated cell free DNA in necrotizing enterocolitis
坏死性小肠结肠炎甲基化细胞游离 DNA 的无创分析
- 批准号:
10577705 - 财政年份:2021
- 资助金额:
$ 58.99万 - 项目类别:
Non-invasive analysis of methylated cell free DNA in necrotizing enterocolitis
坏死性小肠结肠炎甲基化细胞游离 DNA 的无创分析
- 批准号:
10316733 - 财政年份:2021
- 资助金额:
$ 58.99万 - 项目类别:
Modulation of the Intestinal Immune Response in Necrotizing Enterocolitis
坏死性小肠结肠炎肠道免疫反应的调节
- 批准号:
10543597 - 财政年份:2018
- 资助金额:
$ 58.99万 - 项目类别:
Modulation of the Intestinal Immune Response in Necrotizing Enterocolitis
坏死性小肠结肠炎肠道免疫反应的调节
- 批准号:
10468084 - 财政年份:2018
- 资助金额:
$ 58.99万 - 项目类别:
Modulation of the Intestinal Immune Response in Necrotizing Enterocolitis
坏死性小肠结肠炎肠道免疫反应的调节
- 批准号:
10001502 - 财政年份:2018
- 资助金额:
$ 58.99万 - 项目类别:
Aryl hydrocarbon receptor signaling in the pathogenesis of necrotizing enterocolitis
坏死性小肠结肠炎发病机制中的芳基烃受体信号传导
- 批准号:
9220912 - 财政年份:2017
- 资助金额:
$ 58.99万 - 项目类别:
Novel Anti-Inflammatory Properties of Breast Milk in Necrotizing Enterocolitis
母乳在坏死性小肠结肠炎中的新型抗炎特性
- 批准号:
8820360 - 财政年份:2014
- 资助金额:
$ 58.99万 - 项目类别:
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