Structural and molecular markers for detection and monitoring of pediatric fibrostenotic Eosinophilic Esophagitis

用于检测和监测小儿纤维狭窄性嗜酸性食管炎的结构和分子标记

• 批准号: 9751839
• 负责人: CALIES D Menard-Katcher
• 金额: $ 18.97万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-12 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751839
• 关键词: Address; Adrenal Cortex Hormones; Adult; Advisory Committees; Aftercare; Age; Allergens; Assessment tool; Award; Biological Markers; Biopsy; Child; Childhood; Chromosome Mapping; Chronic; Clinical; Clinical Assessment Tool; Clinical Sciences; Colorado; Complication; Data; Deglutition; Deglutition Disorders; Detection; Development; Diagnostic; Disease; Endoscopic Ultrasonography; Endoscopy; Eosinophilic Esophagitis; Epithelium; Esophageal; Esophageal Diseases; Esophageal Stenosis; Esophageal mucous membrane; Esophagus; Fibrosis; Food; Funding; Future; Gastrointestinal Diseases; Gene Expression Profile; Gene Proteins; Genes; Goals; Guidelines; Histologic; Inflammation; Inflammatory; Knowledge; Measurement; Measures; Medical; Mentors; Molecular; Molecular Profiling; Monitor; Mucous Membrane; Newly Diagnosed; Outcome; Pathogenesis; Pathologic; Patient Monitoring; Patients; Pediatric Hospitals; Pediatrics; Personal Satisfaction; Phenotype; Plant Roots; Population; Prevalence; Quality of life; RNA; Recurrence; Reporting; Research; Research Personnel; Resistance; Risk; Sample Size; Severities; Steroids; Stratification; Structure; Thick; Tissues; Training; Universities; career; career development; clinical phenotype; cohort; disease natural history; electric impedance; evidence base; experience; gastrointestinal; genetic signature; health care service utilization; imaging probe; improved; indexing; individual patient; individualized medicine; innovation; medical schools; molecular marker; new therapeutic target; next generation; next generation sequencing; novel; novel marker; patient oriented research; patient stratification; patient subsets; phenotypic biomarker; potential biomarker; professor; programs; protein expression; research and development; response; success; targeted treatment; tool; transcriptome sequencing; treatment response

PROJECT SUMMARY This K23 proposal describes a 5-year career development and research program for Dr. Calies Menard-Katcher, an Assistant Professor at the University of Colorado School of Medicine (CU SOM) and a subspecialist within the Gastrointestinal Eosinophilic Diseases Program at Children's Hospital Colorado. This K23 will provide the candidate necessary support to launch a successful career in patient-oriented research in eosinophilic gastrointestinal diseases. Building on prior research experience and preliminary data, she is investigating the fibrostenotic phenotype of pediatric Eosinophilic Esophagitis (EoE) by means of complimentary and advanced assessment tools including functional luminal impedance (FLIP) and gene analyses. This K23 application includes the following components: Research: EoE, a chronic, allergen triggered esophageal disease has emerged as one of the most common causes of swallowing problems in children and adults. Esophageal stricture, also termed fibrostenotic EoE (FS-EoE), has emerged as the major complication of EoE. This phenotype has worse clinical outcomes and may be more resistant to current treatments. Evidence suggests that clinically meaningful assessment of the FS esophagus is unlikely to be captured by current clinical assessment tools. Alternative strategies are needed to assess esophageal function and the impact of remodeling beyond the mucosa to advance understanding of disease mechanism and improve targeted therapies. Endoscopic assessment with FLIP and endoscopic ultrasound (EUS) can provide this approach. Paired with RNA sequencing to identify novel FS-EoE associated genes, this proposal will provide critical advancement in the study of the FS-EoE phenotype. We hypothesize structural measurements of the esophagus and molecular markers of tissue remodeling will distinguish FS-EoE from non-FS EoE in pediatric subjects. We will determine distensibility of the esophagus in pediatric FS-EoE compared to inflammatory non-FS-EoE in relation to other clinical features of EoE (Aim 1), identify a gene signature defining pediatric FS-EoE (Aim 2) and assess changes in structural and molecular features in response to medical treatment (Aim 3). Results from this novel research will provide significant impact by identifying never before reported structural, functional and molecular signatures of pediatric FS-EoE. Career Development: Dr. Menard-Katcher's short-term goal is to obtain the training required to become an independent investigator with R01 funding to address important questions that will lead to better understanding of the pathogenesis and management of EoE. This training award will allow for development of expertise in endoscopic assessment of EoE phenotypes, next generation sequence interpretation and early assessment of potential biomarkers. Glenn T. Furuta, MD, the primary mentor for this proposal, is a nationally recognized investigator and clinical expert in the field of eosinophilic GI diseases (EGIDs). An advisory committee of co-mentors will provide additional key guidance for the success of the proposed research and the candidate's transition to independence. In addition Dr. Menard-Katcher will continue didactic training, including completion of a Master's in Clinical Sciences, to support her goals.

项目摘要 该K23提案描述了Calies博士的职业发展和研究计划为期5年。 Menard-Katcher，科罗拉多大学医学院（CU SOM）的助理教授和 科罗拉多州儿童医院的胃肠道嗜酸性疾病计划中的专科医生。这 K23将为候选人提供必要的支持，以启动以患者为导向研究的成功职业 嗜酸性胃肠道疾病。在先前的研究经验和初步数据的基础上，她是 通过调查小儿嗜酸性食管炎（EOE）的纤维雌激素表型 免费和高级评估工具，包括功能腔内阻抗（FLIP）和基因 分析。该K23应用程序包括以下组件： 研究：EOE是一种慢性过敏原引发的食管疾病 儿童和成人吞咽问题的常见原因。食道狭窄，也称为纤维雌激素 EOE（FS-EOE）已成为EOE的主要并发症。该表型的临床结果较差 并且可能对当前治疗更具抵抗力。有证据表明对临床意义的评估 FS食道不太可能被当前的临床评估工具捕获。替代策略是 需要评估食道功能以及超出粘膜以外的重塑的影响以促进 了解疾病机制并改善靶向疗法。内窥镜进行翻转和 内窥镜超声（EUS）可以提供这种方法。与RNA测序配对以识别新型FS-EOE 相关的基因，该建议将在FS-EOE表型的研究中提供关键的进步。 我们假设组织的食道和分子标记的结构测量值 重塑将使FS-EOE与儿科受试者中的非FS EOE区分开。我们将确定可扩展性 与其他临床特征相比，小儿FS-EOE的食道 EOE（AIM 1），确定定义小儿FS-EOE（AIM 2）的基因签名并评估结构的变化 和分子特征响应医疗（AIM 3）。这项新研究的结果将提供 通过鉴定以前从未报道过的结构，功能和分子特征来实现重大影响 小儿FS-EOE。 职业发展：Menard-Katcher博士的短期目标是获得成为所需的培训 R01资金的独立调查员，以解决重要的问题，这将导致更好 了解EOE的发病机理和管理。该培训奖将允许开发 内窥镜表型，下一代序列解释和早期的内窥镜评估方面的专业知识 评估潜在的生物标志物。该提议的主要指导者Glenn T. Furuta医学博士是全国性的 公认的嗜酸性胃肠道疾病（EGID）领域的研究者和临床专家。咨询 联合会委员会将为拟议研究的成功提供其他关键指导和 候选人向独立过渡。此外，Menard-Katcher博士将继续进行教学培训，包括 完成临床科学硕士学位，以支持她的目标。