CORE C: Biorepository and Tissue Material Characterization Core

核心摘要 该计划项目补助金（PPG）的首要假设集中在无序的作用， 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 食管是运输团，更深入地了解流体动力学和应变/应力 食管壁的关系是了解食管疾病的关键。大剂量输注 异常是大多数食管症状和并发症的原因，并且该过程高度 取决于食管壁的力学。食管糜烂只是食管癌的一小部分， 食道中的食团转运机制以及食团调节与其如何 通过非收缩食管推进可能比蠕动活力降低更重要。的 在吞咽期间从口咽输送的丸剂必须被调节 在食管壁的机械状态下，可以对应变/应力关系产生显著影响。因此，在本发明中， 我们已经提出了一个PPG，重点是全面了解壁扩张性如何能够 改变大剂量输注和症状。项目1将着重于确定IKKβ/NFκB在促进细胞凋亡中的作用。 减少嗜酸性食管炎（EoE）的扩张性，并评估STAT 3在促进萎缩中的作用 和硬皮病中的纤维化。人类研究将在明确定义的EoE表型中进行， 硬皮病和生物储存和组织材料表征核心（CORE C）将是至关重要的， 为这些研究收集和准备标本。此外，我们还将确定 在组织材料表征子核心中测量的材料特性与 项目1动物研究期间定义的目标。核心C也将非常重要， 为数学模型和虚拟疾病景观提供了重要信息 正常受试者和各种疾病状态的特性将是模型的重要输入。的 用于模型的样本将包括微观和宏观尺度的测量，组织将 通过内窥镜活检和手术后患者丢弃的组织获得。虽然主要角色 核心C将通过在生物生理学领域内开发的模型支持项目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 在模型中生成和细化机械生物标志物，以预测团注输送和症状严重程度。

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.