Autoimmune Regulation of GPCR Function

G protein-coupled receptors (GPCRs) play crucial roles in many biological functions in our body and they are the target of about 30% of all approved drugs.

Despite advancements in technology and our understanding of molecular pharmacology, we still have much to learn about these important receptors.

This includes how autoreactive antibodies (AAbs) circulating in blood can regulate in the function of GPCRs and how this contributes to human disease.

We successfully established a world-unique approach for studying full-length GPCRs for their potential to interact with other membrane proteins and antibodies, confirming their functional integrity and quality.

Our knowledge about > 200 GPCRs allows uncover new meachanism for how AAbs recognize interacting GPCRs and how this regulates the function of GPCRs in an organ-specific manner.

To address this, we willAdapt our current multiplexed analysis framework to the analysis of body fluidsDetermine the autoimmune-recognition of GPCR interactomes in longitudinal cohorts of healthy and diseased donorsReveal organ-specific description of the immune-regulation of interacting GPCRsAs an outcome, we will elucidate how GPCRs can be regulated by ligand binding, membrane interactions, and immune recognition.

This will provide new learnings about the function of GPCRs, shed more light on the role of GPCRs in human health and disease, and lead to the development of more specific drugs with fewer side effects.