The Rockefeller University

Identification of post-translation drivers of immune cell misregulation

Purpose

Methods for exerting control over relative quantities and activation states of different immune cell populations have the potential to positively impact autoimmunity cancer neurodegeneration infection and other human diseases. While large-scale transcriptional analyses have been invaluable for enhancing our understanding of the molecular complexity of immune cell misregulation the extent to which they correlate with changes in protein biochemistry to create a landscape of new opportunities for targeting and selectively manipulating diverse immune cell states with small molecules remains largely unexplored. Furthermore the production of alternatively spliced protein isoforms(changes in RNA splicing) or additional changes following protein biosynthesis (also called post-translational modifications) that are associated with immune pathologies are also frequently poorly understood. This study aims to address this knowledge gap by applying advanced platforms that take advantage of chemical modification of proteins isolated from immune cells and further analysis of these modifications using modern mass-spectrometry tools to uncover previously overlooked alternative splicing or post-translational drivers of immune pathologies and leverage this knowledge for the development of advanced small molecule modulators of immune protein function that form chemical bonds with the respective protein targets.

Condition

• Normal immunity