• With regard to stem cell identity and location in pancreas and liver, we aim to employ a series of novel markers to aid stem cell identification which is presently proving intractable, particularly in the pancreas.
• Concurrently we aim to identify the stem cell niche through examination of signaling pathways (Wnts, Hhs and Notch/Delta) at the mRNA and protein level; and study the role of particular non-parenchymal sub-populations through their selective deletion (collaboration with Stuart Forbes and John Iredale, Edinburgh). These endeavors will be supported by our studies of mitochondrial (mt) DNA mutations that accumulate with age within our cells, elucidating patterns of cellular inheritance and clonal expansion in the normal and diseased human pancreas and liver, and high-resolution synchotron radiation-based Fourier transform infrared microspectroscopy that detects subtle intracellular changes in macromolecules based upon variations in levels of absorption of infrared radiation, appearing to be a robust means of identifying stem cells - collaboration with The University of Lancaster.
• We are currently generating a transgenic mouse model using an inducible Cre-loxP system based upon the CK19 promoter to investigate the possible ductal origin of b–cells.
• We have several collaborations with groups both within and outwith ICMS, including investigations into the Accelerator Hypothesis in the NOD mouse model of T1D and the potential of transplanted bone marrow cells to undergo vasculogenesis in tissue regeneration in inflammatory bowel disease and diabetes.
• In collaboration with David Fine (Southampton) we are developing a murine model of pancreatitis and fibrosis, building upon our previous studies in the liver that proposed that the bone marrow was a major source of fibrogenic cells and that the genotype of the bone marrow could influence the liver's fibrogenic response to injury.
• We are also investigating cancer stem cells in human pancreatic cell lines, and are looking at the roles of stellate (niche) cells (from both pancreas and liver) in modulating cancer stem cell behavior (collaboration with Albert Geerts, Vrije Universiteit, Brussels).

Website:

http://www.icms.qmul.ac.uk/Profiles/Diabetes/Alison%20Malcolm.htm