Longitudinal Cohort/Sheppard

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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.