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）相关的早期风险因素，IBD的生物标志物， 肠道炎症和肠道微生物组多样性丧失。候选人：此应用程序的主要目标 是为了支持Manasi Agrawal博士的职业发展成为一个独立的以病人为导向的研究者， IBD的分子流行病学领域。Agrawal博士的职业目标是成为一名研究人员和领导者， 识别IBD的可改变的早期风险因素，风险预测并最终预防IBD。博士 Agrawal提出的培训活动有五个领域：1）高级和生命过程流行病学，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） 科学和赠款写作。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。 彼得，西奈山遗传学和基因组科学系临时主席， 翻译组学和数据科学，以及Feinstein IBD中心主任Jean-Frederic Colombel博士， 西奈山是IBD发病机制、预测和临床和转化研究的全球专家 预防环境：西奈山伊坎医学院有着悠久的传统， 研究，是NIH资助的前20所医学院之一。西奈山胃肠病学分部 一直被《美国新闻与世界报道》认为是美国十大部门之一， IBD研究和临床护理的国际领导者。研究：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， 发病率，医疗费用和无法治愈。IBD的发病机制涉及早期生命危险因素，但这些因素并不 这阻碍了早期干预和预防。最新数据表明，IBD之前 肠道炎症、微生物组多样性丧失和独特的蛋白质组特征。IBD风险 预测模型将揭示IBD的发病机制，帮助识别高危个体，并指导治疗和 预防战略。此外，确定IBD危险因素对肠道炎症的影响， 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）推导和验证模型，以预测CD和UC的风险，使用早期生命非， 遗传风险因素（2）确定早期IBD风险因素是否与肠道炎症和损失相关 肠道微生物组多样性以及基于其预测模型的IBD风险特征与肠道 （3）确定脐带血清中的炎性蛋白生物标志物是否与母体炎症相关， IBD状态和母亲及其后代的肠道炎症。我们将学习丹麦语 Aim 1和MECONIUM的基于人群的队列研究，MECONIUM是一个新的妊娠妇女纵向队列， 不具有IBD的小鼠及其后代用于目的2和3。在此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的发病机制和预防工作。