Ilia Droujinine, PhD

Secreted proteins coordinate functions of organs and organisms, and compose a yet uncharacterized communication network. For example, in homeostasis, fat-derived adipokines leptin and adiponectin serve as inter-organ secreted metabolic regulators, and in behavior, major urinary proteins serve as inter-organism excreted pheromones regulating aggression. Secreted factors are also relevant for disease: resulting from poorly-characterized dysfunctional inter-organ signaling, obesity affects 40% of the US population (https://www.cdc.gov/obesity/data/adult.html). Despite their relevance for understanding novel biological processes and diseases, identifying the secreted proteins involved has been challenging. Existing analysis methods have serious limitations that preclude comprehensive identification of low-abundance factors and their origins and destinations. Thus, many additional physiologically- and disease-relevant factors remain to be identified. To address this, our lab broadly aims to apply novel high-throughput quantitative approaches we developed to inter-organ and inter-organism communication, in order to understand the nature of the signals involved, which tissue(s) they originate from and target, their functions, and how they are regulated in stress or disease.

We use mice as our primary model system, with validation in human datasets and systems.

We established an in vivo global proteomic platform using BirA*G3 to investigate secreted protein trafficking between organs in Drosophila, and identified a fat body (similar to mammalian liver and adipose tissues) conserved secreted protein that regulates muscle activity. This protein acts on muscles through the interaction with a specific receptor. Due to the success of the BirA*G3 method, we have developed and characterized inducible BirA*G3 mice that we are now using to characterize interorgan communication proteins and peptides. We use these mice to determine secreted proteins regulated by physiological and pathophysiological perturbations, as well as the functions and mechanisms of the identified secreted proteins.

Secreted proteins also coordinate functions of organisms. Animals use chemical cues from their environment and conspecifics to inform decisions necessary for survival. Much is known about how small volatile molecules and pheromones guide behavior; however, whether and how other molecules secreted by conspecifics can influence behavior is unclear. Our research aims to uncover the roles of secreted proteins and peptides in this process.

Projects for new lab members:

• Identification of novel interorgan communication factors in homeostasis and stress in mammals
• Identification of novel interorganism communication factors in homeostasis and stress in mammals
• Mechanistic characterization of novel conserved interorgan and interorganism secreted peptides