CORE C: Biorepository and Tissue Material Characterization Core

CORE C：生物样本库和组织材料表征核心

• 批准号: 10200794
• 负责人: Nirmala P Gonsalves
• 金额: $ 4.17万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200794
• 关键词: Animals; Atrophic; Biological; Biological Markers; Biomechanics; Biopsy Specimen; Blood; Bolus Infusion; Clinical Data; Collection; Complex; Data; Data Collection; Data Set; Deglutition; Development; Disease; Disease model; Endoscopic Biopsy; Ensure; Eosinophilic Esophagitis; Esophageal Diseases; Esophageal Tissue; Esophagus; Feces; Fibrosis; Foundations; Goals; Histologic; Human; Lead; Link; Liquid substance; Measurement; Measures; Mechanics; Minor; Modeling; Molecular; Operative Surgical Procedures; Oral cavity; Oropharyngeal; Pathogenesis; Patients; Peristalsis; Phenotype; Physiological; Play; Process; Program Research Project Grants; Property; Research Personnel; Research Subjects; Role; Scleroderma; Severities; Signal Transduction; Solid; Specimen; Stomach; Stress; Study Subject; Symptoms; Techniques; Tissue Procurements; Tissues; base; biobank; clinical phenotype; data warehouse; disease phenotype; experimental study; human tissue; in silico; mathematical model; mechanical behavior; mechanical properties; member; pressure; prevent; response; success; synergism; virtual

CORE SUMMARY The overarching hypothesis of this program project grant (PPG) is focused on the role of disordered esophageal wall mechanics in the pathogenesis of esophageal diseases. Given that the primary purpose of the esophagus is to transport bolus, a more in depth understanding of fluid dynamics and the strain/stress relationship of the esophageal wall is crucial to understanding esophageal diseases. Bolus transport abnormalities are the cause of most esophageal symptoms and complications and this process is highly dependent on the mechanics of the esophageal wall. Esophageal peristalsis is only a small component of the bolus transport mechanism in the esophagus and the interplay between bolus accommodation and how it is propelled through the non-contracting esophagus is likely more important than reduced peristaltic vigor. The bolus delivered from the oropharynx during swallowing must be accommodated and even minor perturbations in the mechanical state of the esophageal wall can have dramatic effects on strain/stress relationship. Thus, we have proposed a PPG focused on developing a comprehensive understanding of how wall distensibility can alter bolus transport and symptoms. Project 1 will focus on determining the role of IKKβ/NFκB in promoting reduced distensibility in eosinophilic esophagitis (EoE) and assessing the role of STAT 3 in promoting atrophy and fibrosis in scleroderma. Human studies will be performed in well-defined phenotypes of EoE and scleroderma and the Biorepository and Tissue Material Characterization CORE (CORE C) will be crucial in collecting and preparing the specimens for these studies. Additionally, we will also determine whether the material properties measured in the Tissue Material Characterization sub-CORE are correlated with activity of the targets defined during the animal studies in Project 1. CORE C will also be extremely important in providing crucial information for the mathematical models and Virtual Disease Landscape as the material properties in normal subjects and various disease states will be important inputs into the models. The specimens used for the model will be comprised of micro- and macros-scale measurements and tissue will be obtained through endoscopic biopsies and discarded tissue in post-surgery patients. Although the primary role for CORE C will be to support Project 1 and Project 3 through the models developed within the Biophysiologic Modeling Core (CORE B), Projects 2 and 4 will benefit indirectly from CORE C as the data collected will generate and refine the mechanical biomarkers in the models to predict bolus transport and symptom severity.

核心摘要 该计划项目拨款 (PPG) 的总体假设侧重于无序的作用 食管壁力学在食管疾病发病机制中的作用。鉴于其主要目的 食道是输送食团的，更深入地了解流体动力学和应变/应力 食管壁的关系对于了解食管疾病至关重要。推注运输 异常是大多数食管症状和并发症的原因，这个过程高度 取决于食管壁的力学。食管蠕动只是其中很小的一部分 食道中的食团输送机制以及食团调节之间的相互作用以及它是如何进行的 通过非收缩性食管推进可能比蠕动活力降低更重要。这 必须适应吞咽过程中从口咽部输送的丸剂，甚至轻微的干扰 食管壁的机械状态会对应变/应力关系产生巨大影响。因此， 我们提出了 PPG，重点是全面了解壁膨胀性如何影响 改变推注运输和症状。项目 1 将重点确定 IKKβ/NFκB 在促进 嗜酸性食管炎 (EoE) 的扩张性降低并评估 STAT 3 在促进萎缩中的作用 和硬皮病的纤维化。人类研究将在明确的 EoE 表型中进行 硬皮病以及生物样本库和组织材料表征核心 (CORE C) 将在以下方面发挥关键作用： 收集和准备这些研究的标本。此外，我们还将确定是否 在组织材料表征子核心中测量的材料特性与以下物质的活性相关： 项目 1 中动物研究期间确定的目标。CORE C 在以下方面也极其重要： 为数学模型和虚拟疾病景观提供重要信息作为素材 正常受试者和各种疾病状态的特性将是模型的重要输入。这 用于模型的样本将由微观和宏观尺度的测量组成，组织将由 通过内窥镜活检和手术后患者丢弃的组织获得。虽然是主要角色 CORE C 将通过生物生理学内部开发的模型来支持项目 1 和项目 3 建模核心（CORE B）、项目 2 和 4 将间接受益于 CORE C，因为收集的数据将 生成并完善模型中的机械生物标志物，以预测推注运输和症状严重程度。