Grant: Project Grant

The interaction between the immune system and its metabolic environment is an important determinant of immune cell function. Upon activation, inflammatory leukocytes shift their metabolism to aerobic glycolysis to meet their biosynthetic and functional needs e.g. enhanced production of inflammatory mediators. While the mechanisms underlying this metabolic reprogramming are emerging, little is known on how metabolic alterations translate into distinct immunological phenotypes and functions. The innate immune system is our first line of defense against microbial invasion, tissue injury and cellular transformation. Among its arsenals are evolutionary conserved sensors of 'danger' signals, highly expressed in myeloid cells that defend the organism from pathogens and noxious insults by inducing protective responses such as inflammation and cell death. The proposed research project explores how the activation of innate immunity contributes to myeloid cell metabolic reprogramming and reciprocally how metabolic adaptations molecularly regulate myeloid cell functions in inflammatory diseases and tumorigenesis. We focus on the Hexosamine Biosynthetic Pathway, a nutrient sensor fueled by glucose and glutamine and explore a) its role in the survival, activation and function of myeloid cells; and b) its targets in inflammation and cell death regulation.