Targeting fumarate hydratase as metabolic gateway to ferroptosis sensitization

B03 will study how metabolic disturbances, particularly reduced fumarate hydratase (FH) activity, influence lymphomagenesis. FH loss leads to fumarate accumulation, which disrupts BCR signaling and sensitizes cells to ferroptosis. Previous findings show that combining monomethyl fumarate (MMF) with ferroptosis inducers effectively kills DLBCL cells, especially in ABC-DLBCL with high FH expression. The project will explore how FH loss and GPX4 inhibition affect DLBCL progression and therapy response, using in vitro and in vivo models to develop metabolism-targeted treatment strategies.