Risk Prediction of Symptomatic Gallbladder Disease

项目总结/摘要 这K 01职业发展奖申请人是训练有素的遗传流行病学家，他的研究已经 全基因组关联研究 （GWAS）是胃肠道疾病如结直肠腺瘤和胆石病的一种新的治疗方法。他最近领导了一个 一项在GWAS荟萃分析中发现胆结石疾病新遗传标记的研究， 国际同行。在这份提案中，候选人寻求继续他在胆囊疾病方面的工作， 致力于将“组学”研究的知识应用于临床，为病人提供个性化护理。他计划 开发基于代谢组学的生物标志物，以预测症状性胆囊疾病的风险。随后他将 确定它们在预测胆囊切除术患者症状持续性方面的临床有效性，以及 这些生物标记物工具使用数学模拟模型的成本效益。总体 该建议的假设是代谢组学特征可以准确区分具有胆汁型的患者 胆囊切除术更有可能从胆囊切除术中受益的疼痛， 没必要这一提议将使他能够将他的培训从以人口为基础的环境扩大到病人 以研究为导向，并获得比较有效性分析的经验。为了完成这项建议， 候选人将需要在决策科学，以病人为导向的研究和 代谢组学他将受益于一个多学科指导委员会， 胃肠病学、临床流行病学、健康决策科学、生物标志物 流行病学和代谢组学。他的训练计划，在他的指导下制定的 委员会，将包括教学课程在HSPH的目标，以获得流畅的关键概念， 这些训练场。候选人的主要导师安德鲁·T·陈先生在以下方面有既定的往绩记录： 有效地指导研究员和初级教师走向成功的学术生涯。他的研究顾问 委员会不仅将提供方法方面的专门知识，而且还将提供辅导支持、指导和关键建议。 迄今为止，他们的研究重点是癌症风险中的基因-环境相互作用， 反馈以 确保候选人向独立过渡 .研究环境， 包括MGH临床和转化流行病学单位，MGH胃肠病学分部，Channing 哈佛临床和转化科学中心和哈佛T H网络医学部 Chan公共卫生学院将提供大量的合作资源，相关的高级课程， 在这一关键的发展时期，为候选人提供研讨会和其他教学培训机会。 通过这个奖项，候选人将实现他的长期目标，成为一个独立的翻译 研究者，并在临床环境中建立研究计划，特别关注胃肠道 疾病

PROJECT SUMMARY/ ABSTRACT This K01 career development award applicant is trained as a genetic epidemiologist and his research has genome wide association studies (GWAS) of gastrointestinal diseases such as colorectal adenoma and gallstone disease. He recently led a study that identified novel genetic markers of gallstone disease in a GWAS meta-analyses within 10 international cohorts. In this proposal, the candidate seeks to continue his work on gallbladder disease, and work on application of knowledge from `omic' studies, into the clinic for individualized patient care. He plans to develop metabolomics based biomarkers to predict the risk of symptomatic gallbladder disease. He will then determine their clinical effectiveness in predicting persistence of symptoms in cholecystectomy patients, and the cost-effectiveness of these biomarker tools using mathematical simulation models. The overarching hypothesis of this proposal is that metabolomic signatures can accurately distinguish patients with biliary-type pain that are more likely to benefit from cholecystectomy from those for whom cholecystectomy may be unnecessary. This proposal will allow him to expand his training from the population-based setting to patient oriented research, and gain experience in comparative effectiveness analyses. To complete this proposal, the candidate will require additional training in the areas of decision sciences, patient oriented research and metabolomics. He will benefit from a multidisciplinary mentoring committee, consisting of internationally recognized experts in gastroenterology, clinical epidemiology, health decision sciences, biomarker epidemiology, and metabolomics. His training plan, developed with close supervision of his mentoring committee, will include didactic coursework at HSPH with the objective to gain fluency with key concepts in these training areas. The candidate's primary mentor Dr. Andrew T. Chan has an established track record of effectively mentoring fellows and junior faculty towards successful academic careers. His research advisory committee will not only provide methodological expertise, but also mentoring support, guidance and critical focused so far on gene-environment interactions in the risk of cancers, and feedback to ensure the candidate's transition towards independence . The research environment, which includes MGH Clinical and Translational Epidemiology Unit, MGH Division of Gastroenterology, the Channing Division of Network Medicine, The Harvard Clinical and Translational Science Center and the Harvard T H Chan School of Public Health will provide vast collaborative resources, relevant advanced course-work, seminars and other didactic training opportunities for the candidate during this critical developmental period. Through this award, the candidate will realize his long term goal of becoming an independent translational investigator, and establishing a research program in a clinical setting, with specific focus on gastrointestinal diseases.