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Our research focuses on understanding the genomic and metabolic networks that underlie liver progenitor differentiation during embryonic development and adult homeostasis.

Patterning during embryonic development requires the correct cell fate decisions to occur at the right time and in the right place. This strict temporal and spatial regulation of differentiation needs to integrate multiple signals including the metabolic needs of the cell as it undergoes cell fate transitions. Beyond the critical role of glucose metabolism to provide energy and biosynthetic molecules for cellular processes, metabolism can exert signalling functions that have not only permissive but also instructive roles in promoting differentiation. Our goal is to dissect the genetic and metabolic signals underlying differentiation of liver progenitor cells towards hepatocytes and ductal cells during development, regeneration and disease.

To do this we use liver organoid culture systems derived from embryonic and adult tissues to recapitulate liver progenitor differentiation in vitro. Liver organoids provide a tangible system in which we can assess and manipulate the activity of specific signalling and metabolic pathways during differentiation free from the influence of other cells or cues in the organism. Using both human and mouse models we aim to 1) characterise the metabolic changes associated with liver differentiation; 2) understand how metabolic rewiring actively/passively influences cell fate choices; 3) understand how perturbations to genomic and metabolic networks lead to disease.