Project Summary/Abstract: Macrophage polarization is involved in the progression of normal physiological and pathological processes. The near universal importance of macrophage has led to widescale assessment of the genomic and proteomic to classify their function. However, it is still a challenge to measure macrophage polarization in real time such as in the context of assessing the status of a biomaterial implant or the efficacy of a nanoparticle drug delivery system in a solid tumor. Our preliminary data show that bioluminescence microscopy is able to deliver the protein expression data valuable for macrophage polarization combined the cell tracking capability of traditional imaging system. This research program will address the current gap in real-time assessment of macrophage polarization by 1) further developing the technology to measure macrophage polarization dynamics using bioluminescence microscopy and 2) assessing the intrinsic and extracellular environmental stimuli that are most important for sensing macrophage polarization in a diseased environment context. To accomplish these goals, we will employ ex-vivo culture systems and live bioluminescence imaging. This work will identify novel strategies for measuring macrophage polarization and validate the importance of analyzing polarization in a disease context. Ultimately, this research will lead to new strategies for synthetic biology development, enhancement of diagnostic testing and development of new therapeutic targets. In addition, the knowledge and tools developed can be applied to other cells where polarization is paramount such as stem cell differentiation, chemoattraction, and cell metabolism.

Project Narrative The ability to monitor therapy success during the course of the treatment is incredibly valuable and still a big challenge for the implementation of biomaterials like metal/electrical implants and nanoparticle-based drug delivery. This research will help us understand how develop therapies that are personalized to the patient’s unique macrophage functional signature. This work could lead to the development of better real-time biological sensors which could improve patient outcomes.