Institution: VIB (Center for Cancer Biology). Leuven, Belgium
Team: Laboratory of Tumor Inflammation and Angiogenesis.
PI: Massimiliano Mazzone
Objectives: Fatty acid oxidation is a hallmark of M2-like macrophages in both infectious diseases and the tumor microenvironment. The NAD-dependent deacetylase sirtuin-1, Sirt1, which is induced by hypoxia and a downstream target of AMPK, is a regulator of fatty acid metabolism and regulates HIF pathway. The role of Sirt1 in tumor-associated macrophages is unexplored. We aim to study how Sirt1 integrates TAM metabolism and the immune response orchestrated by TAMs. By looking at the regulation of HIFs by acetylation, we will focus on the metabolic and phenotypic rewiring of hypoxic TAMs, hoping to control their immunosuppressive, pro-metastatic, and pro-angiogenic phenotype. Expected Results: we aim to re-educate TAMs metabolically and functionally by targeting Sirt1 genetically and pharmacologically. Eventually, downstream targets to HIF regulation by Sirt1 will be functionally validated for targeted therapies in mouse models of cancer.