Research

Our research is focused on the crosstalk between metabolism and tumorigenesis outlining metabolic reprogramming in cancer. We combine metabolomics and genetic approaches to identify metabolic pathways essential for disease progression with the aim of developing new treatment strategies. The development of treatments that target tumor metabolism is receiving renewed attention, with several potential drugs targeting metabolic pathways currently under development. Cancer cells have a remarkably different metabolism from that of the tissues from which they are derived. They exhibit an altered metabolism that allows them to sustain higher proliferative capacity and resist cell death signals, particularly those mediated by increased oxidative damage. However, this means that they are more nutrient hungry and excrete more waste products than normal tissues, resulting in a build-up of metabolites inside the cell and the formation of a more hostile microenvironment. Recently, metabolites that can promote tumorigenesis by altering gene expression and the epigenome have been identified. These 'oncometabolites' include the tricarboxylic acid (TCA) cycle metabolites succinate and fumarate, whose levels are elevated in rare tumors with succinate dehydrogenase and fumarate hydratase mutations, respectively. From an anabolic perspective, we recently implicated acetate as a source for acetyl-CoA production, especially under hypoxia. Acetyl-CoA is the precursor for the synthesis of fatty acids and cholesterol and a substrate for protein acetylation, including histone modifications. We demonstrated that pharmacologically targeting the acetate capturing enzyme ACSS2 is an effective cancer therapeutic approach, particularly under metabolically stressful environment, typically observed in solid tumors.

To learn more, view our publications list here.