Longitudinal Cohort/Sheppard

项目总结（见说明）： IPF临床药物开发因缺乏机制相关终点而受阻。纵向队列核心的主要目的是为项目1-3提供纵向临床数据和生物样本（血液和BAL），用于识别ER应激、TGFB激活和EMT的候选机械信息分子标志物。机械信息分子标记将是 在受试者选择中非常有用，并作为项目1-3中确定的潜在药物制剂的早期研究的终点，允许更快速和有效地评估生物效应。使用来自该核心的血液和BAL，我们将证明候选的机械信息分子标志物在IPF患者的临床可及区室中是可测量的。将比较IPF和对照受试者之间的分子标志物水平，并将其与基线人口统计学和临床数据相关联。 还将评估候选机械信息分子标志物的纵向稳定性。预期由纵向队列核心支持的实验将导致鉴定ER应激、avp 6介导的TGFB活化和EMT的新的、机制信息分子标记，其在IPF患者中易于测量并且随时间相对稳定。 作为这些试验中的机械敏感终点，将在该转化计划项目资助的第二个5年期间进行。

PROJECT SUMMARY (See instructions): Clinical drug development in IPF is hindered by the lack of mechanistically-relevant endpoints. The primary objective of the Longitudinal Cohort Core is to supply longitudinal clinical data and biological samples (blood and BAL) to Projects 1-3 to be used in the identification of candidate mechanistically-informative molecular markers of ER stress, TGFB activation, and EMT. Mechanistically-informative molecular markers would be extremely useful in subject selection and as endpoints in early phase studies of potential drug agents identified in Projects 1-3, allowing for more rapid and efficient assessment of biological effect. Using the blood and BAL from this core, we will show that candidate mechanistically-informative molecular markers are measurable in clinically-accessible compartments of patients with IPF. Molecular marker levels will be compared between IPF and control subjects, and correlated with baseline demographic and clinical data. The longitudinal stability of candidate mechanistically-informative molecular markers will also be assessed. It is anticipated that experiments supported by the Longitudinal Cohort Core will result in the identification of novel, mechanistically-informative molecular markers of ER stress, avp6-mediated TGFB activation, and EMT that are easily measurable in patients with IPF and are relatively stable over time.Such molecular markers will help identify appropriate subjects for future early-phase clinical trials of drug agents and could serve as mechanistically-sensitive endpoints in these trials, to be conducted during the second 5 years of this translational program project grant.