Organisms must constantly adapt their physiology and metabolism to maintain optimal development and adult performance throughout their lives. Achieving this refined homeostasis requires precise, coordinated communication across all organs and tissues. Increasingly, the innate immune system is emerging as a key player that orchestrates tissue homeostasis, moving beyond its traditional role in fighting infection. We focus on macrophages, long-lived immune cells found in virtually all organs and tissues across metazoans. As highly sensitive sensor cells, macrophages detect and integrate diverse environmental signals to orchestrate adaptive cellular responses critical for the growth, remodeling, and function of specialized tissues. These features suggest that macrophages act as essential local and systemic information hubs, rather than simply serving as the body's first line of defense against pathogens.
Our lab aims to explore novel inter-organ communication mechanisms where macrophages act as key players in regulating systemic homeostasis during both steady state and pathophysiological conditions. We hypothesize that macrophages serve as central information hubs that link environmental signals to whole-body physiology. Our research seeks to answer two fundamental questions:
1. Sensing and Signaling: How do macrophages utilize their extensive array of membrane receptors to sense both external and internal stimuli? Furthermore, how do they respond by disseminating growth factors to stimulate and modulate the physiology of surrounding and distal organs?
2. Integration and Priming: How do macrophages integrate diverse stimuli simultaneously to prime a specific, appropriate adaptive response across the organism?
Our Experimental Approach:
To address these questions, we use the fruit fly, Drosophila melanogaster, as our primary animal model. This powerful system allows us to combine:
Furthermore, we apply environmental challenges to Drosophila to actively modulate macrophage behavior and systemic physiology, providing a dynamic view of their regulatory role.
Translational Vision and Collaboration:
We focus on identifying fundamental regulatory mechanisms governed by macrophages that are evolutionarily conserved and potentially extrapolatable to all metazoans. To ensure the broad impact of our findings, we actively seek collaborations with other labs to corroborate our discoveries in vertebrate models, including mouse, zebrafish, and human cells.
