Dr Tom MacVicar - Mitochondrial Reprogramming in Cancer


Remarkable cancer cell metabolic flexibility and plasticity enable tumours to grow and combat chemotherapy. Mitochondria are essential organelles that support tumour adaptation to altered metabolic demands and environmental challenges. Accordingly, mitochondrial form and function are dynamically reprogrammed during tumorigenesis. For instance, the levels of key mitochondrial inner membrane proteins, including metabolite transporters, are fine tuned in response to nutrient and oxygen availability to support cancer cell proliferation and survival.

Metabolite transporter proteins are required to exchange small molecules including amino acids and nucleotides between the mitochondria and the rest of the cell. The tightly regulated coupling of cytosolic and mitochondrial metabolic reactions across the inner mitochondrial membrane represents an essential but poorly understood facet of tumour metabolism. Our goal is to identify mitochondrial metabolite transporters that control cancer progression using genetic screening approaches in 3D tumour models combined with genetically engineered mouse models. We will also investigate how regulated mitochondrial nucleotide transport and metabolism contribute to tumorigenesis and cancer cell responses to nucleotide-analogue chemotherapy. These studies will improve our basic understanding of mitochondrial reprogramming in tumours and may identify novel therapeutic targets for cancers that depend on metabolic flexibility and plasticity, including pancreatic cancer.