Modelling foetal liver development and disruption using pluripotent stem cells

It is well established that exposure to cigarette smoke, ingredients of commonly used plastics, and being overweight can cause disease in the human population. They also are known to programme disease in the developing fetus and which can present at birth, or become apparent during post-natal development. The focus of the project is to better understand the threat that these factors pose to human health in utero. We will study the developing liver, using stem cell derived cell based models. Those models have already provided a greater understanding of the effects of maternal smoking on liver development and human metabolism, providing critical proof of concept (Villarin et al 2017 Archives of Toxicology; Lyall et al 2018, Philosophical Transactions B). In these studies we wish to further our understanding of the gene regulatory networks that are altered following exposure. We believe that such fundamental advances have the potential to improve human health during the lifetime of the individual. In particular, the output from these studies will provide novel mechanistic understanding of human liver disease, with the focus on improving fetal health, and thereby reducing the need for medical and social interventions post-birth.