The Natural History of Pediatric Crohn's Disease

描述(由申请人提供)： 该奖项将为候选人提供获得临床研究培训、教育工具、科学技术和指导的机会，这些将有助于她成为儿科IBD研究的独立研究员以及IBD领域的重要贡献者。职业发展计划将包括通过K30计划进行的教学学习、当地GCRC培训和研究道德行为方面的培训，以及研究计划中提议的研究活动。环境：有了K23奖项和机构承诺所提供的受保护的时间，候选人将能够将75%的时间投入到教学部分(K30计划)和完成下文所述的科学提案，该奖项的导师带来了对职业生涯和研究计划的成功至关重要的专业知识。Cedars-Sinai的常见疾病遗传学主任将提供培训和资源，以扎实地了解遗传研究，Cedars-Sinai的免疫生物学研究所主任将提供机会，将免疫学领域的新知识纳入拟议的研究，并将指导这一项目中的免疫工作。此外，GCRC将提供进行所有基因检测所需的资源和设施。研究：儿童发病的克罗恩病通常被描述为具有侵袭性的临床病程，使患者在病程早期出现疾病并发症，通常需要积极的内科和/或外科治疗。该项目提出，存在确定或预测儿童克罗恩病更具侵袭性的病程的可识别的风险因素。目的是进行一项前瞻性纵向队列研究，以确定儿童期起病的克罗恩病的自然病史，并分析人口统计学、遗传学、免疫和环境对侵袭性疾病表型和疾病进展的影响。该项目的具体目标是1)从北美西部地区建立一个具有良好临床特征的患者队列，以研究新发克罗恩病儿童的疾病进展或自然病史，以及2)确定是否存在可识别的人口、遗传、免疫学和/或环境风险因素影响新发克罗恩病儿童侵袭性疾病表型和疾病进展。来自北美西部地区的总共400名患者将被纳入研究。主要程序将包括收集关于临床和环境病史的数据，以及用于基因分型和测试免疫反应的血液样本。收集的数据将存储在一个安全的儿科IBD数据库中。主要结果测量包括复杂疾病行为发生的频率和时间，以及风险标记物和确定的患者结果之间的关联。确定儿童发病的克罗恩病的自然病史并描述侵袭性疾病进展的潜在决定因素将导致长期的努力，以确定该病的临床前自然病史，并开发干预研究以防止临床疾病发展为临床并发症。

DESCRIPTION (provided by applicant): This award will afford the candidate an opportunity to acquire the clinical research training, educational tools, scientific techniques and mentorship that will be instrumental for her to succeed as an independent investigator in Pediatric IBD research as well as an important contributor to the field of IBD. The career development plan will include didactic learning through the K30 program, local GCRC training and training in the ethical conduct of research as well as the research activities proposed in the research plan. Environment: With the protected time afforded by the K23 award and the institutional commitment, the candidate will be able to devote 75% of her time to the didactic component (K30 program) and to completing the scientific proposal described below The mentors for this award bring with an expertise critical to the success of the career and research plan. The Director of Common Diseases Genetics at Cedars-Sinai will provide the training and resources to acquire a solid understanding of genetic research and the Director of the Immunobiology Institute at Cedars-Sinai, will provide the opportunities to incorporate newfound knowledge in the field of immunology into the proposed research and will direct the immune work to be done in this project. Additionally the GCRC will provide the resources and facilities that will be necessary to conduct all genetic testing. Research: Childhood-onset Crohn's disease is often described as having an aggressive clinical course such that patients develop disease complications early in the disease course, often necessitating aggressive medical and/or surgical management. This project proposes that there are identifiable risk factors that determine or predict a more aggressive disease course of Crohn's disease in children. The objective is to conduct a prospective longitudinal cohort study to define the natural history of childhood-onset Crohn's disease and to analyze the demographic, genetic, immune and environmental influences on aggressive disease phenotypes and disease progression. The specific aims of this project are 1) to establish a clinically well characterized patient cohort from the Western Region of North America to study disease progression or natural history of children with new-onset Crohn's disease and 2) To determine if there are identifiable demographic, genetic, immunologic and/or environmental risk factors that influence aggressive disease phenotypes and disease progression in children with new-onset Crohn's disease. A total of 400 patients from the Western Region of North America will be enrolled. Principal procedures will include data collection on clinical and environmental history as well as blood sampling for genotyping and testing immune response. Collected data will be stored in a secured relational pediatric IBD database. Primary outcome measures include frequency and time to occurrence of complicating disease behaviors and the associations between markers of risk and defined patient outcome. Defining the natural history of childhood-onset Crohn's disease and delineating the potential determinants of aggressive disease progression will lead to long term efforts to define the preclinical natural history of the disease, and to develop intervention studies to prevent progression of clinical disease to clinical complications.