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: 9242812
• 负责人: CALIES D Menard-Katcher
• 金额: $ 19.33万
• 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/9242812
• 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 Investigator; Clinical Sciences; Colorado; Complication; Data; Deglutition; Deglutition Disorders; Detection; Development; Diagnostic; Disease; Endoscopic Ultrasonography; Endoscopy; Eosinophilic Esophagitis; Epithelium; Esophageal; Esophageal Diseases; Esophageal Stenosis; Esophagus; Fibrosis; Food; Funding; Future; Gastrointestinal Diseases; Gene Expression Profile; Gene Proteins; Genes; Goals; Guidelines; Histologic; Inflammation; Inflammatory; Knowledge; Lead; 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; Staging; Steroids; Stratification; Thick; Tissues; Training; Ultrasonography; 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; innovation; medical schools; molecular marker; new therapeutic target; next generation sequencing; novel; novel marker; patient oriented research; patient stratification; patient subsets; 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.

项目概要 这项 K23 提案描述了 Calies 博士的 5 年职业发展和研究计划 Menard-Katcher，科罗拉多大学医学院 (CU SOM) 助理教授 科罗拉多儿童医院胃肠道嗜酸性粒细胞疾病项目的亚专科医师。这 K23 将为候选人提供必要的支持，以在以患者为导向的研究领域开启成功的职业生涯 嗜酸粒细胞性胃肠道疾病。基于之前的研究经验和初步数据，她 通过以下方法研究小儿嗜酸性食管炎 (EoE) 的纤维狭窄表型 补充和先进的评估工具，包括功能性管腔阻抗 (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，已成为最常见的食管疾病之一。 儿童和成人吞咽问题的常见原因。食管狭窄，也称为纤维狭窄 EoE (FS-EoE) 已成为 EoE 的主要并发症。这种表型的临床结果更差 并且可能对当前的治疗更有抵抗力。有证据表明，有临床意义的评估 当前的临床评估工具不太可能捕获 FS 食管。替代策略是 需要评估食管功能以及粘膜以外重塑的影响以推进 了解疾病机制并改进靶向治疗。使用 FLIP 进行内窥镜评估 超声内镜 (EUS) 可以提供这种方法。与 RNA 测序配对鉴定新型 FS-EoE 相关基因，该提案将为 FS-EoE 表型的研究提供重要进展。 我们假设食道的结构测量和组织的分子标记 重塑将区分儿科受试者中的 FS-EoE 和非 FS EoE。我们将确定可扩展性 儿科 FS-EoE 食管与炎症性非 FS-EoE 食管的比较与其他临床特征的关系 EoE（目标 1），确定定义儿科 FS-EoE 的基因特征（目标 2）并评估结构变化 以及对药物治疗的分子特征（目标 3）。这项新颖研究的结果将提供 通过识别以前从未报道过的结构、功能和分子特征来产生重大影响 儿科 FS-EoE。 职业发展：Menard-Katcher 博士的短期目标是获得成为 由 R01 资助的独立调查员来解决重要问题，从而带来更好的结果 了解 EoE 的发病机制和治疗。该培训奖将允许发展 EoE 表型内窥镜评估、下一代序列解释和早期 评估潜在的生物标志物。 Glenn T. Furuta 医学博士是该提案的主要导师，是一位全国性的 嗜酸细胞性胃肠道疾病 (EGID) 领域公认的研究者和临床专家。咨询 共同导师委员会将为拟议研究的成功提供额外的关键指导 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。