PI: Bryan Bryson, Department of Biological Engineering, MIT
Macrophages are sentinel cells of the immune system and execute a wide array of functions across a variety of tissues in cancer, wound healing, and infection. Using algorithms for integration of single-cell RNA sequencing data, we have identified a population of macrophages expressing the surface receptor TREM2 that are associated with a diverse range of diseases. Previous literature suggests that TREM2 plays an immunoregulatory role in modulating the function of murine macrophages. We hypothesize that TREM2 plays an immunoregulatory role in human macrophages as well. Current biological tools are not well equipped to tackle this question in human macrophages given existing challenges in genetic engineering of these cells. Here, we propose the optimization of robust CRISPR-based methodologies for primary human macrophages to study the regulation and function of TREM2. These findings will be foundational in determining the potential of regulating TREM2 in disease as a novel target for immunotherapy.