The main aim of our research is to understand the molecular mechanisms that direct cells towards a pancreatic fate. We use embryonic stem (ES) cells and induced pluripotent stem (iPS) cells to determine how cells are restricted first to endoderm and then pancreas. We are also investigating if specialised cells from adult tissue, such as skin cells, can be switched directly into pancreatic cells in a process called direct reprogramming.
We hope our studies will contribute to the development of protocols for producing large numbers of insulin-producing cells for use in future cell replacement therapies for diabetes.
The molecular processes that underpin specification of the endodermal and pancreatic cell lineage are incompletely characterized. Embryonic stem cells possess the ability to differentiate into all cell types of the developing and adult organism and as such they have proven useful as a tractable model system with which to dissect mechanisms of lineage specification.
We have recently developed a highly efficient differentiation regime for the generation of endoderm from naïve embryonic stem cells. Using this model system we have identified a critical role GSK3 inhibition in the regulation of key endodermal genes. We will continue to use this system to investigate the signaling, transcriptional and epigenetic processes that underpin definitive endoderm lineage specification. Our major goal is to determine how major intracellular signaling pathways operate and co-operate to drive the gene regulatory network to specify first endoderm and then pancreatic lineages.
We are also investigating if human pancreatic progenitor cells can be captured and expanded ex vivo. Analysis of human pancreatic progenitors in culture will aid our understanding of the onwards maturation process from foetal progenitor to fully mature, functional cell.
University of Edinburgh Chancellor’s Fellowship 2013-2018.