Ilia Droujinine, PhD

The secreted proteome represents a poorly characterized interorgan communication network that is central in the etiology of various metabolic disorders including obesity and type 2 diabetes. Despite this, the composition and activity of interorgan communication networks and their impact on disease remain poorly defined, as it has historically been difficult to identify the secreted proteins due to their low abundance and lack of information on their organ(s) of origin and destination. To address this, we established in mice a conditional BirA*G3 engineered biotin ligase system that labels all secreted proteins within the endoplasmic reticulum of one organ, allowing identification of proteins that traffic to distal organs using affinity enrichment and quantitative mass spectrometry. Using this approach, we identified hundreds of proteins trafficking from intestinal epithelium to distal organs, including known low-abundance (~pg/mL) hormones such as GLP-1. Furthermore, we identified and characterized novel diet- and obesity-regulated intestine-secreted proteins specifically acting on adipose tissue. In this talk, I will describe proteins secreted by the intestine in fasting or obesity that traffic to adipose tissues and impact systemic glucose and lipid metabolism. Our methods are widely applicable to proteins secreted from other organs, establishing a new strategy to broadly define the whole-body interorgan communication networks. Our lab continues to develop and apply approaches to decipher the secreted ligands and their mechanisms involved in communication between multiple organs and in various diseases.