Identifying Genomic and Microbial Contributions in Early Childhood-Inflammatory Bowel Disease
确定基因组和微生物在儿童早期炎症性肠病中的作用
基本信息
- 批准号:10629411
- 负责人:
- 金额:$ 18.53万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-16 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:2 year old6 year oldAchievementAdultAgeChildChildhoodChronic DiseaseCollaborationsComplexCoupledCross-Sectional StudiesDataDefectDevelopmentDevelopment PlansDiagnosisDiseaseDisease susceptibilityEnrollmentEnvironmentEnvironmental ExposureEnvironmental Risk FactorEtiologyFrequenciesFutureGenesGeneticGenomicsImmuneImmune responseImmune systemImmunologicsIncidenceInflammationInflammatory Bowel DiseasesIntestinesLeadLifeMentorsMorbidity - disease rateNewly DiagnosedOligogenic TraitsOnset of illnessPathogenesisPathogenicityPathway interactionsPatientsPhenotypePopulationPredispositionPrevalenceProcessQuality of lifeRefractoryResearchResearch PersonnelResearch ProposalsRoleSNP arraySeverity of illnessShotgunsStructureSusceptibility GeneTechnologyTimeTrainingTreatment outcomeUnderserved PopulationVariantWorkage groupbiomarker identificationcareercareer developmentconventional therapydisease diagnosisdisease phenotypedisorder riskearly childhoodearly life exposureearly onsetexome sequencinggut microbiomegut microbiotaillness lengthimprovedinfancyinnovationinsightlarge datasetsmetagenomic sequencingmicrobialmicrobial communitymicrobial signaturemicrobiomemicrobiotamolecular sequence databasemultidisciplinarynovelpolygenic risk scorerare variantresearch and developmentresponseskill acquisitionskillsstool samplesymposiumtargeted treatmenttherapeutic targettherapeutically effectivetherapy designtranslational study
项目摘要
Project Summary/Abstract
Inflammatory bowel disease diagnosed before age 6 years can be distinguished from older onset pediatric and
adult IBD by its unique phenotype of severe morbidity, poor response to conventional therapies, greater duration
of disease, and its rapidly increasing prevalence. This population is further divided into those diagnosed <2 year
of age, infantile IBD, and children diagnosed between 2 and 6 years old, whom we refer to as early childhood
IBD for this proposal. While pediatric IBD is a complex polygenic disease, we and others have identified causative
monogenic defects in infantile IBD. However, little is understood about the pathogenic mechanisms in early
childhood IBD. The underlying hypothesis of this proposal is that patients with early childhood IBD have a unique
host genomic background coupled with early life exposures. This interaction leads to a dysfunctional dynamic
between the immune response and the intestinal microbial community structure. The PI will utilize this career
development and research plan in order to gain skills and establish collaborations which will allow her to develop
future translational studies leveraging large data sets to identify future therapeutic targets to improve treatment
outcomes for early childhood-IBD.
Using cutting edge technology, we will generate genomic and microbiome data to study children with early
childhood IBD. In Aim 1, the PI will identify the role of both rare and low frequency variants using whole exome
sequencing and calculate the polygenic risk score based on known IBD susceptibility loci in order to characterize
the genetic burden of the early childhood IBD phenotype. In Aim 2, stool samples will be collected during the
first 8 weeks of initiating IBD treatment in 100 newly diagnosed early childhood IBD patients in addition to
collecting data regarding environmental exposures. Shotgun metagenomic sequencing will be used to discern
the microbial community structure at each time point. The baseline microbiota will be correlated with early life
environmental exposures and the longitudinal microbiota will be analyzed in the context of changing disease
activity. As part of her career development plan, this research plan with allow the PI to refine and acquire skills
with the support of her mentors, receive hands on training from her collaborators, enroll in formal coursework,
and participate in multidisciplinary seminars and conferences to prepare her for a future career as an
independent investigator.
项目摘要/摘要
6岁以前诊断的炎症性肠病可以与年龄较大的儿童和
成人IBD以其独特的表型发病严重,对常规治疗反应差,病程较长
疾病的数量及其迅速增加的流行率。这一群体被进一步划分为确诊2岁的人群。
年龄,婴儿IBD,以及被诊断为2至6岁的儿童,我们称之为早期儿童
IBD支持这项提议。虽然儿童IBD是一种复杂的多基因疾病,但我们和其他人已经确定了病因
婴儿IBD的单基因缺陷。然而,对早期的致病机制知之甚少。
儿童炎症性肠病。这一建议的基本假设是,早期儿童IBD患者有独特的
宿主基因组背景与早期生命暴露相结合。这种相互作用导致了一种功能失调的动态
免疫反应和肠道微生物群落结构之间的关系。私家侦探将利用这一职业
制定开发和研究计划,以便获得技能并建立合作关系,使她能够
未来的转化性研究利用大型数据集来确定未来的治疗目标,以改善治疗
儿童早期结局--IBD。
使用尖端技术,我们将产生基因组和微生物组数据来研究早期儿童
儿童炎症性肠病。在目标1中,PI将使用整个外显子组来识别稀有和低频变体的作用
根据已知的IBD易感基因座对多基因风险得分进行测序和计算,以便表征
儿童早期IBD表型的遗传负担。在目标2中,大便样本将在
100例新诊断的儿童早期IBD患者开始IBD治疗的前8周
收集有关环境暴露的数据。鸟枪式元基因组测序将用于识别
每个时间点的微生物群落结构。基线微生物区系将与早期生命相关
环境暴露和纵向微生物区系将在变化的疾病的背景下进行分析
活动。作为她职业发展计划的一部分,这项研究计划允许PI改进和获得技能
在导师的支持下,接受合作者的动手培训,参加正式的课程学习,
并参加多学科研讨会和会议,为她未来的职业生涯做好准备
独立调查员。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The Treatment of Pediatric Inflammatory Bowel Disease with Biologic Therapies.
- DOI:10.1007/s11894-020-00773-3
- 发表时间:2020-06-15
- 期刊:
- 影响因子:0
- 作者:Conrad MA;Kelsen JR
- 通讯作者:Kelsen JR
Bowel-associated dermatosis-arthritis syndrome in a child with very early onset inflammatory bowel disease.
- DOI:10.1111/pde.14544
- 发表时间:2021-05
- 期刊:
- 影响因子:1.5
- 作者:Havele, Sonia A.;Clark, Ashley K.;Oboite, Michelle;Conrad, Maire A.;Perman, Marissa J.;Rubin, Adam I.;Treat, James R.
- 通讯作者:Treat, James R.
Pediatric Global Health in Children with Very Early-Onset Inflammatory Bowel Disease.
患有极早发炎症性肠病的儿童的儿科全球健康。
- DOI:10.1093/jpepsy/jsab035
- 发表时间:2021
- 期刊:
- 影响因子:3.6
- 作者:Holbein,ChristinaE;Plevinsky,Jill;Patel,Trusha;Conrad,MaireC;Kelsen,JudithR
- 通讯作者:Kelsen,JudithR
Editorial to Temporal Gut Microbial Changes Predict Recurrent Clostridium difficile Infection in Patients With and Without Ulcerative Colitis.
颞部肠道微生物变化预测患有和不患有溃疡性结肠炎的患者复发艰难梭菌感染的社论。
- DOI:10.1093/ibd/izz336
- 发表时间:2020
- 期刊:
- 影响因子:4.9
- 作者:Conrad,MaireA;Kelsen,JudithR
- 通讯作者:Kelsen,JudithR
Clostridioides difficile Infection in Pediatric Inflammatory Bowel Disease: A Clinician's Dilemma.
小儿炎症性肠病中的艰难梭菌感染:临床医生的困境。
- DOI:10.1093/jpids/piab069
- 发表时间:2021
- 期刊:
- 影响因子:3.2
- 作者:Conrad,MáireA;Kelsen,JudithR
- 通讯作者:Kelsen,JudithR
{{
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 }}
Maire Abraham Conrad其他文献
Maire Abraham Conrad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 }}
{{ truncateString('Maire Abraham Conrad', 18)}}的其他基金
Identifying Genomic and Microbial Contributions in Early Childhood-Inflammatory Bowel Disease
确定基因组和微生物在儿童早期炎症性肠病中的作用
- 批准号:
10162582 - 财政年份:2019
- 资助金额:
$ 18.53万 - 项目类别:
Identifying Genomic and Microbial Contributions in Early Childhood-Inflammatory Bowel Disease
确定基因组和微生物在儿童早期炎症性肠病中的作用
- 批准号:
10408105 - 财政年份:2019
- 资助金额:
$ 18.53万 - 项目类别:
相似海外基金
Psychosocial factors as potential moderators of the association between prenatal stress from the Fort McMurray wildfire and social emotional development in 5-6 year old children
心理社会因素作为麦克默里堡野火产前压力与 5-6 岁儿童社会情绪发展之间关系的潜在调节因素
- 批准号:
467237 - 财政年份:2021
- 资助金额:
$ 18.53万 - 项目类别:
Studentship Programs
Mechanisms of Sustained Selective Attention in 2- to 6- Year-Old Children
2至6岁儿童持续选择性注意力的机制
- 批准号:
7739271 - 财政年份:2009
- 资助金额:
$ 18.53万 - 项目类别:
Stage 1 Treatment Development with Homeless Mothers and their 2-6 Year Old Childr
无家可归的母亲及其 2-6 岁儿童的第一阶段治疗发展
- 批准号:
7627037 - 财政年份:2009
- 资助金额:
$ 18.53万 - 项目类别:
Mechanisms of Sustained Selective Attention in 2- to 6- Year-Old Children
2至6岁儿童持续选择性注意力的机制
- 批准号:
7921601 - 财政年份:2009
- 资助金额:
$ 18.53万 - 项目类别:
Stage 1 Treatment Development with Homeless Mothers and their 2-6 Year Old Childr
无家可归的母亲及其 2-6 岁儿童的第一阶段治疗发展
- 批准号:
8037547 - 财政年份:2009
- 资助金额:
$ 18.53万 - 项目类别:
Stage 1 Treatment Development with Homeless Mothers and their 2-6 Year Old Childr
无家可归的母亲及其 2-6 岁儿童的第一阶段治疗发展
- 批准号:
8035834 - 财政年份:2009
- 资助金额:
$ 18.53万 - 项目类别: