Probing inflammation dynamics via multi-modal tracking and control of engineered macrophages

PROJECT SUMMARY Inflammation is a fundamental biological process that coordinates immune responses to infection, injury, and disease. Understanding the dynamics of inflammation is essential for deciphering how immune responses shift from protective to pathological states. Our research aims to provide mechanistic insights into these processes to uncover therapeutic opportunities for modulating the immune system. Macrophages, due to their phenotypic plasticity and ability to regulate inflammation, play a pivotal role in this context. Additionally, macrophage trafficking—encompassing their movement and localization within tissues—is critical to understanding inflammation dynamics. A core focus of our laboratory is to develop non-invasive imaging and control techniques that allow for real-time visualization and modulation of macrophages. With support from this MIRA, we will develop and validate a new class of engineered macrophages capable of both tracking and modulating inflammation in vivo. By equipping macrophages with markers detectable across multiple imaging modalities— including ultrasound, MRI, and optical imaging—we aim to achieve a comprehensive, multimodal view of macrophage behavior at different spatial and temporal scales. This innovative approach will significantly enhance our ability to probe inflammation dynamics and pave the way for targeted interventions that precisely modulate macrophage activity. Furthermore, we will employ focused ultrasound technology to control the functional responses of engineered macrophages in remote control, establishing a novel framework for understanding and managing inflammation in living systems. This integrated strategy not only aims to enhance our understanding of macrophage dynamics within various disease settings but also serves as a foundation for innovative macrophage-based therapeutics, specifically aimed at reprogramming macrophage functions for restoring immune balance in diseased environments. Our ultimate vision is to create a theranostic platform using living cells as both therapeutic agents and imaging probes, enabling compatibility with bioacoustic, biophotonic, and biomagnetic tracking methods and setting a new standard for the precision treatment of inflammation-related diseases.