Early-life Risk Factors for Inflammatory Bowel Disease

炎症性肠病的早期危险因素

• 批准号: 10284609
• 负责人: Manasi Agrawal
• 金额: $ 19.14万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-12 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10284609
• 关键词: 5 year old; Advisory Committees; Affect; American; Antibiotics; Area; Award; Biological Markers; Biometry; Chronic; Clinical; Clinical Research; Cohort Analysis; Country; Crohn' s disease; Data; Data Analyses; Data Science; Department chair; Digestive System Disorders; Early Intervention; Environment; Epidemiology; Etiology; Event; Funding; Future; Gastroenterology; Generations; Genetic; Genetic Risk; Goals; Grant; Health Care Costs; Immigrant; Immune; Immunologics; Individual; Infant; Infection; Inflammatory; Inflammatory Bowel Diseases; International; Intestinal Diseases; Investigation; K-Series Research Career Programs; Leukocyte L1 Antigen Complex; Life; Life course epidemiology; Light; Longitudinal cohort; Maternal-Fetal Transmission; Mediating; Mentors; Mentorship; Methodology; Modeling; Molecular Epidemiology; Morbidity - disease rate; Mothers; New York; Onset of illness; Outcome; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Perinatal; Persons; Phase; Positioning Attribute; Pregnant Women; Prevention; Prevention strategy; Preventive; Proteomics; Reporting; Research; Research Methodology; Research Personnel; Risk; Risk Factors; Science; Serum; Socioeconomic Status; Techniques; Testing; Therapeutic; Time; TimeLine; Training; Training Activity; Translational Research; Ulcerative Colitis; United States National Institutes of Health; Work; Writing; base; career; career development; clinical care; cohort; disability; disease diagnosis; disease transmission; disorder risk; early life exposure; genome sciences; gut microbiome; indexing; inflammatory disease of the intestine; innovation; insight; medical schools; microbiome; news; non-genetic; novel; offspring; patient oriented; population based; pre-clinical; predictive marker; predictive modeling; prenatal; protein biomarkers; proteomic signature; risk prediction; risk prediction model; skills

This project will evaluate early-life risk factors associated with inflammatory bowel diseases (IBD), biomarker of intestinal inflammation and loss of gut microbiome diversity. Candidate: The primary objective of this application is to support Dr. Manasi Agrawal’s career development into an independent patient-oriented investigator in the field of molecular epidemiology of IBD. Dr. Agrawal’s career goal is to become a researcher and leader in the identification of modifiable early-life risk factors for IBD, risk prediction and eventually, prevention of IBD. Dr. Agrawal’s proposed training activities are in five areas: 1) advanced and life-course epidemiology, 2) advanced biostatistical methodology 3) predictive biomarker analysis, 4) principles of immunological data analysis and 5) scientific and grant writing. To achieve this, she has assembled a mentoring and advisory team led by Dr. Inga Peter, Interim Chair of the Department of Genetics and Genomic Sciences at Mount Sinai and an expert in translational -omics and data science, and Dr. Jean-Frederic Colombel, Director of the Feinstein IBD Center, Mount Sinai, a global expert in clinical and translational investigation of IBD pathogenesis, prediction and prevention. Environment: The Icahn School of Medicine at Mount Sinai has a strong tradition of outstanding research and is one of the top 20 medical schools in NIH funding. The Mount Sinai Division of Gastroenterology is consistently considered one of the top 10 divisions in the country by US News and World Report and is an international leader in IBD research and clinical care. Research: IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic, progressive, immune-mediated disease of the intestinal tract with significant morbidity, healthcare costs and has no cure. IBD pathogenesis involves early-life risk factors, but these are not well-understood, which impedes early intervention and prevention. Newer data suggest IBD is preceded by intestinal inflammation, loss of microbiome diversity and distinct proteomic signatures. Developing IBD risk prediction models will shed light on IBD pathogenesis, help identify at-risk individuals, and guide therapeutic and preventive strategies. In addition, determining the impact of IBD risk factors on intestinal inflammation and microbiome changes will provide further insights in IBD pathogenesis and the relevance of these changes. Therefore, our specific aims are to (1) derive and validate models to predict CD and UC risk using early-life non- genetic risk factors (2) determine if early-life IBD risk factors are associated with intestinal inflammation, and loss of gut microbiome diversity as well as correlate IBD risk signature based on its prediction model with intestinal inflammation (3) determine if inflammatory protein biomarkers in the cord serum are associated with maternal IBD status and with intestinal inflammation in the mothers and their offspring. We will study the Danish population-based cohort for Aim 1, and MECONIUM, a novel longitudinal cohort of pregnant women with and without IBD and their offspring for Aims 2 and 3. The general approaches and skills developed during this award can be applied to future studies to understand better IBD pathogenesis and toward preventive efforts.

该项目将评估与炎症性肠病 (IBD) 相关的早期危险因素、炎症性肠病的生物标志物 肠道炎症和肠道微生物多样性丧失：该应用的主要目标。 是为了支持 Manasi Agrawal 博士的职业发展，成为一名以患者为中心的独立研究者 Agrawal 博士的职业目标是成为 IBD 分子流行病学领域的研究员和领导者。 识别可改变的 IBD 早期危险因素、风险预测并最终预防 IBD。 阿格拉瓦尔提议的培训活动分为五个领域：1）高级和生命全程流行病学，2）高级 生物统计学方法 3) 预测性生物标志物分析，4) 免疫学数据分析原理和 5) 为了实现这一目标，她组建了一个由 Inga 博士领导的指导和咨询团队。 Peter，西奈山遗传学和基因组科学系临时主席，也是该领域的专家 转化组学和数据科学，以及 Feinstein IBD 中心主任 Jean-Frederic Colombel 博士， Mount Sinai，IBD 发病机制、预测和临床转化研究领域的全球专家 环境：西奈山伊坎医学院有着优良的传统。 是 NIH 资助的前 20 所医学院之一。 一直被《美国新闻与世界报道》评为该国十大分区之一，并且是 IBD 研究和临床护理领域的国际领导者：IBD，包括克罗恩病 (CD) 和 溃疡性结肠炎（UC）是一种慢性、进行性、免疫介导的肠道疾病， IBD 的发病机制涉及生命早期的危险因素，但这些都不是。 较新的数据表明 IBD 发生在 IBD 之前。 肠道炎症、微生物组多样性丧失和独特的蛋白质组学特征导致 IBD 风险。 预测模型将揭示 IBD 发病机制，帮助识别高危个体，并指导治疗和治疗 此外，确定 IBD 危险因素对肠道炎症的影响和 微生物组的变化将为 IBD 发病机制和这些变化的相关性提供进一步的见解。 因此，我们的具体目标是 (1) 推导并验证模型，以使用生命早期非 遗传风险因素 (2) 确定生命早期 IBD 风险因素是否与肠道炎症和丧失相关 肠道微生物组多样性的变化以及基于其预测模型与肠道的 IBD 风险特征的关联 炎症 (3) 确定脐带血清中的炎症蛋白生物标志物是否与母体相关 我们将研究丹麦人的IBD状况以及母亲及其后代的肠道炎症。 目标 1 的基于人群的队列，以及妊娠妇女的新型纵向队列 没有 IBD 及其后代的目标 2 和 3。在该奖项期间开发的一般方法和技能 可以应用于未来的研究，以更好地了解 IBD 发病机制并采取预防措施。