Role of microRNAs in pediatric inflammatory bowel disease

microRNA 在小儿炎症性肠病中的作用

• 批准号: 9196597
• 负责人: Adam Matthew Zahm
• 金额: $ 7.99万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-06 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9196597
• 关键词: Role; microRNAs; pediatric; inflammatory; bowel

 DESCRIPTION (provided by applicant): The objective of this proposal is to provide the applicant with exemplary biomedical research training in the field of pediatric gastrointestinal disease and to prepare the applicant for a career as an independent research scientist. To achieve this objective, a training regimen within the scope of inflammatory bowel disease (IBD) has been developed, consisting of research aims and substantial training activities. IBD is an intestinal disorder characterized by chronic inflammation, resulting in diarrhea, weight loss, growth failure, rectal bleeding, abscesses, strictures, or fistulas. IBD comprises two disease types, Crohn's disease (CD) and ulcerative colitis (UC), and is one of the most serious diseases affecting the health of children; the peak diagnosis period for both CD and UC occurs during childhood. Recently, several studies have described changes in the expression of microRNAs (miRNAs) in the intestine of adults with IBD, yet the role of miRNAs in the disease process has not been described and virtually nothing is known regarding miRNAs in pediatric IBD. Experiments proposed under this award are designed to 1) identify changes in mucosal miRNA expression in pediatric CD, 2) discover mRNAs targeted by intestinal epithelial miRNAs in vitro and in vivo and 3) determine the role of the miR- 194/192/215 family in perpetuating intestinal inflammation in vivo. High-throughput sequencing will be used throughout to quantify miRNA and mRNA levels. Transgenic mice will be designed to specifically inhibit intestinal miR-194/192/215 activity thereby allowing for the discovery of the miRNA-targeted transcriptome and the role of these miRNAs in potentiating intestinal inflammation. The proposed research and training will occur at The Children's Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania (UPENN). The CHOP/UPENN campus provides extraordinary training opportunities for young scientists. An experienced mentoring team has been assembled to guide the scientific activities and to oversee the applicant's acquisition of the professional skills required of an independent scientist. The training plan includes intramural and extramural coursework, training in new methodologies, attendance at national conferences as well as local seminar series, training in the responsible conduct of research, and lectures designed to improve grant writing skills. Overall, the proposed activities will provide the applicant with tools, skills, and discoveries that will serve as the foundation for a successful independent career in gastroenterology research.

 描述（由申请人提供）：本提案的目的是为申请人提供儿科胃肠道疾病领域的示范性生物医学研究培训，并为申请人作为独立研究科学家的职业生涯做好准备。为了实现这一目标，在炎症性肠病（IBD）的范围内的培训方案已经开发，包括研究目标和大量的培训活动。IBD是一种以慢性炎症为特征的肠道疾病，导致腹泻、体重减轻、生长障碍、直肠出血、脓肿、狭窄或瘘管。IBD包括两种疾病类型，克罗恩病（CD）和溃疡性结肠炎（UC），是影响儿童健康的最严重疾病之一; CD和UC的诊断高峰期均发生在儿童时期。最近，几项研究已经描述了成人IBD患者肠道中microRNA（miRNAs）表达的变化，但miRNAs在疾病过程中的作用尚未描述，并且几乎对小儿IBD中的miRNAs一无所知。该奖项下提出的实验旨在1）鉴定儿科CD中粘膜miRNA表达的变化，2）发现体外和体内肠上皮miRNA靶向的mRNA，3）确定miR- 194/192/215家族在体内维持肠道炎症中的作用。高通量测序将用于定量miRNA和mRNA水平。转基因小鼠将被设计为特异性抑制肠道miR-194/192/215活性，从而允许发现miRNA靶向的转录组和这些miRNA在增强肠道炎症中的作用。拟议的研究和培训将在费城儿童医院（CHOP）和宾夕法尼亚大学佩雷尔曼医学院（UPENN）进行。CHOP/UPENN校园为年轻科学家提供了非凡的培训机会。一个经验丰富的指导小组已经成立，以指导科学活动，并监督申请人的收购， 独立科学家所需的专业技能。培训计划包括校内和校外课程、新方法培训、出席全国会议和地方系列研讨会、负责任地开展研究培训以及旨在提高赠款撰写技能的讲座。总的来说，拟议的活动将为申请人提供工具，技能和发现，这将成为胃肠病学研究成功的独立职业生涯的基础。