Luke O'Neill

Luke O'Neill co-founded the immunometabolism field by demonstrating that Krebs cycle metabolites including succinate and itaconate function as signaling molecules that regulate macrophage inflammatory responses, with succinate stabilizing HIF1alpha to drive IL-1beta production and itaconate activating Nrf2 to limit inflammation. His discovery that tumor-associated macrophages accumulate specific metabolites that lock them in immunosuppressive states revealed metabolic reprogramming as a targetable mechanism of immune evasion. He develops itaconate derivatives and succinate dehydrogenase inhibitors as immunometabolic drugs to reprogram tumor-associated macrophages from immunosuppressive to tumoricidal phenotypes.