Investigation of endogenous retroelements in lung disease [OAR project]

National Institute Of Environmental Health Sciences

Investigators

Abstract

This award was received mid-2025 by Dr. Fessler (less than 6 months ago). Since receipt of funds, Dr. Fessler has successfully hired, onboarded, and trained a postbaccalaureate fellow for the project. Under the mentorship of Dr. Fessler and other Institute staff, the fellow has begun optimizing conditions for purification of PBMCs from human donor blood, followed by ex vivo stimulation with a panel of L1-inducing agents and analysis by a panel of PCR primers for confirmation of L1 induction. LPS and trichostatin A have been confirmed to induce L1 mRNA. The fellow has also validated a mass cytometry panel, including an antibody specific for L1 ORF1p in human PBMCs. In addition, extramural collaborator Dr. Nicholas Parrish of Duke has recently completed L1 genotyping calls on ~4700 PEGS subjects, binning them into deciles of L1 copy number. The goal in this pilot phase of the study is to optimize PBMC culture and stimulation conditions for detection of L1 induction. We expect within the next ~4 weeks to then commence recruitment of PBMC donors by L1 copy decile, with an aim to testing whether increasing L1 copy number is associated with increased L1-inducibility and cytokine responses of PBMCs.