Risk Factors and Biomarkers for Diagnosis & Treatment of Eosinophilic Esophagitis

描述（由申请人提供）：候选人是一名胃肠病学家，在以患者为导向的研究方法学方面受过良好的培训，并被证明致力于食管疾病的研究，特别是嗜酸性粒细胞性食管炎（EoE）。候选人的长期职业目标是成为一名独立资助的食管疾病领域的医生科学家，领导一个跨学科的翻译研究团队，连接诊所，内窥镜套件，病理实验室和基础科学实验室。候选人的K23计划的短期职业目标是：1）获得转化研究技术的知识和技能; 2）发展成功领导多学科研究团队的专业技能;和3）产生初步数据和出版物的临界质量，以支持R 01资助申请，并建立EoE独立研究计划。拟议的研究计划，职业发展活动，导师团队和机构环境都是唯一适合帮助申请人实现这些目标。候选人的总体研究目标是更好地了解EoE的流行病学和发病机制，以改善诊断和治疗。EoE是一种快速出现的临床病理学实体，其定义为嗜酸性粒细胞异常浸润至食管粘膜，导致吞咽困难、进行性食管狭窄和食物嵌塞。本研究建议的具体目标是验证我们的EoE诊断风险因素模型，并评估血清嗜酸性粒细胞趋化因子-3和IL-13水平在EoE诊断和治疗监测中的实用性。我们将比较新诊断的EoE患者与非EoE对照，获得基线测量值，治疗后重新评估EoE患者，并重新评估未治疗的对照。待测试的中心前提是：1）临床风险因素，加上非侵入性血清生物标志物，将导致更准确的诊断EoE; 2）非侵入性生物标志物可用于监测治疗反应。为了支持候选人的职业发展，他将在选定的基础科学实验室进行一系列正式实习，重点是特定的转化研究技术，并在分子技术，生物标志物和统计学领域进行高级课程和独立研究应用于公共卫生和流行病学。导师和咨询团队，其中包括国际公认的，独立资助的研究人员，在胃肠道流行病学和转化团队研究（桑德勒），食管疾病和转化研究（沙欣），细胞和分子生理学（亨宁），和EoE发病机制和转化方法（罗森伯格）的专业知识，将指导博士。研究环境，包括转化和临床科学研究所和中心胃肠生物学和疾病在斯坦福大学提供了一个富有成效的，合议和协作的氛围，以追求上述研究和培训目标。在该计划结束时，Dellon博士将成为一名独立的医生-科学家，领导一个多学科的转化研究团队。

DESCRIPTION (provided by applicant): The candidate is a gastroenterologist with strong training in patient-oriented research methodology, and a proven commitment to the study of esophageal diseases, and eosinophilic esophagitis (EoE) in particular. The candidate's long-term career goal is to be an independently funded physician-scientist in the area of esophageal diseases leading a multidisciplinary translational research team bridging the clinic, endoscopy suite, pathology lab, and basic science lab. The candidate's short-term career goals for the K23 program are to: 1) acquire knowledge and skills in translational research techniques; 2) develop the professional skills to successfully lead a multidisciplinary research team; and 3) produce a critical mass of preliminary data and publications to support an R01 grant application and establish a program of independent research in EoE. The proposed research plan, career development activities, mentorship team, and institutional environment are all uniquely suited to assist the applicant in achieving these goals. The candidate's overall research goal is to better understand the epidemiology and pathogenesis of EoE in order to improve diagnosis and treatment. EoE is a rapidly emerging clinicopathologic entity defined by abnormal infiltration of eosinophils into the esophageal mucosa that leads to dysphagia, progressive esophageal stenosis, and food impaction. The specific goals of this research proposal are to validate our model of risk factors for diagnosis of EoE, and to assess the utility of serum levels of eotaxin-3 and IL-13 in diagnosis and monitoring of treatment of EoE. We will compare patients with newly diagnosed EoE to non-EoE controls, obtain baseline measures, reassess EoE patients after treatment, and also reassess untreated controls. The central premises to be tested are that: 1) clinical risk factors, coupled with non-invasive serum biomarkers, will lead to more accurate diagnosis of EoE; and 2) non-invasive biomarkers can be used to monitor treatment response. To support the candidate's career development, he will conduct a series of formal internships in selected basic science labs focusing on specific translational research techniques, as well as pursue advanced coursework and independent study in the areas of molecular techniques, biomarkers, and statistics as applied to public health and epidemiology. The mentorship and advising team, which includes internationally-recognized, independently-funded investigators with expertise in gastrointestinal epidemiology and translational team research (Sandler), esophageal diseases and translational research (Shaheen), cell and molecular physiology (Henning), and EoE pathogenesis and translational methods (Rothenberg), will guide Dr. Dellon's research and career development. The research environment including the Translational and Clinical Sciences Institute and Center for Gastrointestinal Biology and Disease at UNC provides a productive, collegial, and collaborative atmosphere in which to pursue the above research and training goals. At the conclusion of this program, Dr. Dellon will be positioned to be an independent physician-scientist leading a multidisciplinary translational research team.