Risk Factors and Biomarkers for Diagnosis & Treatment of Eosinophilic Esophagitis

用于诊断的危险因素和生物标志物

• 批准号: 8186517
• 负责人: Evan Samuel Dellon
• 金额: $ 18.03万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8186517
• 关键词: Accident and Emergency department; Aftercare; Allergens; Applications Grants; Area; Attention; Award; Basic Science; Biological Markers; Biological Markers; Biology; Biopsy; Blood; Cells; Characteristics; Chemotactic Factors; Clinic; Clinical; Clinical Sciences; Clinical Trials; Consensus; Control Groups; Coupled; Data; Deglutition; Deglutition Disorders; Development Plans; Diagnosis; Disease; Endoscopy; Environment; Eosinophilic Esophagitis; Epidemiology; Esophageal; Esophageal Diseases; Esophageal Stenosis; Esophageal mucous membrane; Food; Funding; Future; Gastroenterologist; Gastroesophageal reflux disease; Goals; Gold; Guidelines; Histologic; Incidence; Infiltration; Institutes; Interdisciplinary Study; Interleukin-13; Internships; Investigation; Knowledge; Lead; Learning; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentorship; Methods; Modeling; Molecular; Monitor; Newly Diagnosed; Pathogenesis; Pathologic; Pathology; Patients; Physicians; Physiology; Positioning Attribute; Prevalence; Principal Investigator; Procedures; Public Health; Publications; Receiver Operating Characteristics; Research; Research Methodology; Research Personnel; Research Proposals; Research Technics; Research Training; Risk; Risk Factors; Scientist; Series; Serum; Specimen; Steroid therapy; Steroids; Techniques; Testing; Tissues; Training; Translational Research; Work; career; career development; chemokine; clinical practice; cytokine; diagnostic accuracy; eosinophil; gastrointestinal; genetic risk factor; human CCL26 protein; improved; infancy; multidisciplinary; novel; patient oriented research; planetary Atmosphere; programs; research and development; response; skills; statistics; treatment response

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. PUBLIC HEALTH RELEVANCE: Eosinophilic esophagitis (EoE), a newly recognized disease with rapidly increasing incidence, prevalence, and recognition, is characterized by the abnormal presence of eosinophils in the esophageal lining, leading to difficulty swallowing, progressive esophageal stenosis, and food impaction. The goal of this and subsequent research is to better understand the risk factors, causes, and biologic markers of EoE in order to improve diagnosis and treatment. The proposed research may impact clinic practice by altering the way in which EoE is both diagnosed and monitored by decreasing the need for repeated costly and invasive procedures.

应聘者描述(由申请人提供)：应聘者为胃肠病专家，在以病人为中心的研究方法方面有很强的培训，并致力于研究食道疾病，特别是嗜酸性食管炎(EoE)。应聘者的长期职业目标是成为一名独立资助的食道疾病领域的内科科学家，领导一个多学科转换研究团队，连接临床、内窥镜检查套件、病理学实验室和基础科学实验室。应聘者对K23项目的短期职业目标是：1)获得翻译研究技术方面的知识和技能；2)发展成功领导多学科研究团队的专业技能；3)产生大量的初步数据和出版物，以支持R01拨款申请，并在EoE中建立独立研究计划。建议的研究计划、职业发展活动、导师团队和机构环境都非常适合帮助申请者实现这些目标。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，以提高诊断和治疗水平。EOE是一种迅速出现的临床病理实体，其特征是嗜酸性粒细胞异常渗入食道粘膜，导致吞咽困难、进行性食道狭窄和食物嵌塞。本研究方案的具体目标是验证我们诊断EoE的危险因素模型，并评估血清eoaxin-3和IL-13水平在EoE诊断和治疗监测中的应用。我们将比较新诊断的EoE患者和非EoE对照组，获得基线测量，在治疗后重新评估EoE患者，并重新评估未治疗的对照组。要测试的主要前提是：1)临床风险因素，加上非侵入性血清生物标记物，将导致更准确的EoE诊断；以及2)非侵入性生物标记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，专注于特定的翻译研究技术，并在应用于公共卫生和流行病学的分子技术、生物标记物和统计学领域进行高级课程和独立学习。指导和咨询团队包括在胃肠道流行病学和翻译团队研究(Sandler)、食道疾病和翻译研究(Shaheen)、细胞和分子生理学(Henning)以及EoE发病和翻译方法(Rothenberg)方面具有专长的国际公认的独立资助的研究人员，将指导Dellon博士的研究和职业发展。北卡罗来纳大学的翻译和临床科学研究所以及胃肠道生物学和疾病中心等研究环境为实现上述研究和培训目标提供了一个富有成效的、合作的和合作的氛围。在这个项目结束时，Dellon博士将成为一名独立的内科科学家，领导一个多学科的翻译研究团队。 公共卫生相关性：嗜酸性食管炎(EoE)是一种新发现的疾病，发病率、患病率和认可度迅速上升，其特征是食管壁中异常存在嗜酸性粒细胞，导致吞咽困难、进行性食道狭窄和食物嵌塞。这项研究和后续研究的目标是更好地了解EoE的危险因素、病因和生物标志物，以便提高诊断和治疗水平。这项拟议的研究可能会通过改变EoE的诊断和监测方式来影响临床实践，减少重复的昂贵和侵入性程序的需要。