Macrophage dysfunction is a hallmark of chronic sterile inflammatory diseases including cancer, atherosclerosis, and obesity/type 2 diabetes. Because macrophages are highly influenced by their environment, it is essential to understand how disease-specific changes to tissues trigger specific pathways in macrophages to drive pathogenesis. Moreover, the relationship between disease-producing macrophage pathways to those required for pathogen clearance is largely unknown, which is important because attempts to therapeutically target macrophages must preserve their host defense function. Comparing and contrasting macrophages across a spectrum of diseases is therefore required to elucidate disease-specific mechanisms, and to develop therapeutics that are both efficacious and safe.Our long-term goal is to develop a robust research program that uses a multi-disease approach to develop a comprehensive understanding of macrophage biology, and translate this mechanistic understanding to develop therapeutics across a spectrum of human disease. To this end, we are developing a new biologic for the treatment of many cancers, a small molecule that restores anti-cancer immunity, and a small molecule that attenuates atherosclerosis.