Signaling of Immune Checkpoints
The immune system normally eliminates early malignant cells, thus preventing tumorigenesis. Immune checkpoints prevent overactivation of the immune system, however tumors exploit these checkpoints to evade detection and clearance. Despite enormous clinical importance, we still have an incomplete understanding of which proteins participate in checkpoint signaling, how phosphorylation regulates checkpoint receptor signaling and how uncharacterized (orphan) checkpoint receptor ligands contribute to negative immune regulation.
We plan to leverage proximity-proteomics and highly advanced mass spectrometry (MS) to study dynamics and aberrations of signaling processes in the context of immune checkpoints, pushing the envelope of existing MS technology. Through our innovative approaches we hope to elucidate ligand-specific differential immune signaling and decode differential phosphorylation in checkpoint signaling with the goal to ultimately better understand how the tumor micro-environment modulates receptor signaling.