Role of hypoxia in tumour cell metabolism (360G-Wellcome-207162_Z_17_Z)

Previous research has shown upregulation of haem oxygenase 1 (HMOX1) in hypoxic cells and tissues. However, we currently do not understand what benefit this confers on hypoxic cells. HMOX1 is the first enzyme involved in the breakdown of haem, releasing carbons as bilirubin/biliverdin, free iron, and oxidising NADPH. We hypothesise that HMOX1 upregulation is required for hypoxic cell viability through permitting metabolic adaptation. The objectives of this project are to elucidate whether knock-down of HMOX1 causes loss of hypoxic cell viability. Additionally, I aim to determine how HMOX1 activity supports mitochondrial metabolic function by tracing the flux of carbons through mitochondrial metabolic pathways in the presence or absence of HMOX1 in normoxic and hypoxic conditions using stable isotope (13C)-enriched glucose or glutamine. Through these studies, I aim to improve understanding of the role of HMOX1 in hypoxic cells , and may provide some evidence to propose HMOX as a potential therapeutic target in cancer.