Genotype to phenotype studies of inherited metabolic liver diseases using human iPSCs
Human induced pluripotent stem cells open up the exciting possibility of patient specific disease modelling in a dish. My work was the first to demonstrate the possibility of recreating disease specific phenotypes for inherited metabolic liver diseases in this manner (JCI 2010, Nature 2011, J Hep 2018). The diseases we have modelled so far are caused by monogenetic inheritance of autosomal recessive traits. Even patients with these mutations however display a broad spectrum of pathological manifestations ranging from being largely asymptomatic to suffering from liver failure requiring organ transplantation. Other genetic and non genetic factors are therefore likely to be at play.
The aim of this project will be to combine a large library of patient specific iPSC lines with the associated clinical health records data to help understand the relationship between observed in vitro phenotypes and human disease manifestation. The long term aim is to use this proof of principle study and build larger studies dissecting out the mechanisms underlying complex multi-genetic liver disorders such as metabolic syndrome /T2DM associated fatty liver disease. In this manner we will advance the field of personalised medicine by providing patient ‘avatars’ in a dish from which we can predict natural disease progression and therapeutic response.
would like to be able to access all health records related to each patient modelled
iPS models, genotype to phenotype