Risk Prediction of Symptomatic Gallbladder Disease

项目摘要/摘要 这位K01职业发展奖申请者接受过遗传流行病学家的培训，他的研究 全基因组关联研究 胃肠道疾病，如结直肠腺瘤和胆石病。他最近领导了一个 在GWAS荟萃分析中发现新的胆石症遗传标记的研究 国际同龄人。在这项提案中，候选人寻求继续他在胆囊病方面的工作，以及 致力于将“经济学”研究中的知识应用于临床，以提供个性化的病人护理。他计划 开发基于代谢组学的生物标记物来预测症状性胆囊病的风险。到时候他会的 确定它们在预测胆囊切除术患者症状持续时间方面的临床有效性，以及 使用数学模拟模型对这些生物标记物工具的成本效益进行评估。最重要的是 这一建议的假设是代谢组特征可以准确地区分胆道类型的患者 对于那些可能接受胆囊切除术的人，更有可能从胆囊切除术中受益的疼痛 没必要。这项提议将使他能够将他的培训从以人群为基础的环境扩展到患者 以研究为导向，并在比较有效性分析方面积累经验。为了完成这项提案， 应聘者将需要在决策科学、以患者为中心的研究和 代谢组学。他将受益于一个由国际社会组成的多学科指导委员会。 在胃肠病学、临床流行病学、健康决策科学、生物标志物方面的公认专家 流行病学和代谢组学。他的训练计划是在他的指导下制定的 委员会，将包括HSPH的授课课程，目的是流利地掌握 这些训练区。候选人的主要导师陈德霖博士在以下方面有既定的记录 有效地指导研究员和初级教员走向成功的学术生涯。他的研究建议 委员会不仅将提供方法上的专业知识，而且还将提供指导支持、指导和关键 到目前为止，重点是癌症风险中的基因-环境相互作用，以及 反馈给 确保候选人向独立的过渡 。研究环境，这是 包括MGH临床和转译流行病学单位，MGH消化内科，Chning 网络医学部、哈佛临床与转化科学中心和哈佛T H 陈氏公共卫生学院将提供大量的合作资源，相关的高级课程工作， 在这个关键的发展阶段，为候选人提供研讨会和其他教学培训机会。 通过这个奖项，候选人将实现他成为一名独立翻译的长期目标 研究人员，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.