The regenerative (proliferative) and senescent (unable to proliferate) status of individual epithelial cellular components in the livers will be studied.
The molecular signatures of the different cell populations in the liver will be characterised to allow a rational understanding of the positive factors that can be used to promote regeneration and the negative inhibitors of regeneration that could be targeted.
For liver, a combination of whole liver gene expression analysis will be combined with laser capture microdissection for gene expression analysis for particular cellular components e.g. hepatocyte and biliary cells that can regenerate parenchyma when severe hepatocyte injury and senescence prevails.
The cellular and molecular features of the epithelial cells in the liver will be characterised and the non-parenchymal cells that help stimulate, control and impede regeneration will also be studied. Data provided by the gene expression analysis will be processed via the central bioinformatics core. This approach will be further developed in the ISAIAH study where paired biopsy analysis will provide detailed transcriptional response patterns to therapeutic interventions. The data will be used to guide future mechanistic studies in rodents and in vitro phenotypic screens to validate targets. The team hope the data will then guide future therapeutic approaches for development by pharma partners or be the subject of future research grant applications.