Group leader: 

James Ross

Position: 

Professor of Liver Cell Biology, Associate Researcher

Contact: 

j [dot] a [dot] ross [at] ed [dot] ac [dot] uk

See also Professor James Ross' personal profile on the University's Clinical Surgery website.

Background
The process of differentiation of an individual hepatocyte from its stem cell origins is still poorly characterised. Information regarding the genetic and proteomic profile of adult, fetal and embryonic stem cell-derived hepatocytes will be valuable in ascertaining how closely in vitro differentiation mimics the in vivo situation. In addition, such information will provide not only basic information on the process of differentiation but may contribute to future use of stem cell-derived liver cells in artificial support devices, in regenerative medicine/transplantation and in cell-based assays in drug discovery/toxicology. We have developed expertise in examining human hepatocyte function and differentiation from fetal stem cells, through fetal hepatocytes to adult hepatocytes and also collaborate on the differentiation of human ES and human iPS cells to the hepatocyte lineage. We are currently investigating the role of the stem cell niche(s) within the developing liver which contribute(s) to stem cell self-renewal and differentiation, the role of placenta-derived factors in influencing stem cell behaviour and the ability of fetal liver stem cells to differentiate along alternative pathways.

Related areas of interest include investigating the mechanisms of liver repair following damage or hypoxic insult and the induction of stress (heat shock) proteins (pre-conditioning) in order to protect from a more severe insult. We continue to investigate the contribution of the liver to the systemic inflammatory response in cancer and cardiovascular disease. We have a particular interest in the systemic inflammation and altered liver metabolism associated with cancer cachexia, in the cell biology of muscle degradation associated with this process and in the possibility of muscle regeneration. We are utilising our expertise in identifying stem cells in fetal liver tissue towards identifying the stem cell component in hepatic, pancreatic and prostatic malignancies.

Approaches and progress
We use a combination of primary human cells and cell lines, human ES and iPS cells and rodent models to examine the differentiation and function of adult and progenitor liver cells. Cell function and cell fate are analysed using molecular, biochemical and proteomic techniques. There are strong collaborative links with Stuart Forbes, John Iredale and Richard Anderson and within our home department (Clinical Surgery - KCH Fearon, SJ Wigmore, RW Parks and OJ Garden) which hosts the Scottish Liver Transplant Unit. We also have strong collaborative involvement with the Centre for Cardiovascular Science and the Centre for Integrative  Physiology.

Imaging and delivery systems
We have designed and manufactured a lipid-encapsulated contrast microbubble which is ultrasonically echogenic at intravascular frequencies (30-40 MHz) (patent filed). Moreover, by incorporating specific ligands into the surface of the microbubbles, we have shown that the microbubbles can be targeted to specific cellular and tissue sites within the vasculature. This development of suitable targeting strategies will aid in delivering site-specific drug or gene delivery. The technology also provides an opportunity to develop combined ultrasound, fluorescent and magnetic resonance imaging contrast agents which can be targeted to specific cell types or employed for stem cell tracking in vivo.

Selected publications

• Lowrie AG, Dickinson P, Wheelhouse N, Stewart GD, Ross AJ, Forster T, Ross JA. 2011. Proteolysis-inducing factor core peptide mediates dermcidin-induced proliferation of hepatic cells through multiple signalling networks. Int J Oncol. 39(3):709-18.
• Hay DC, Pernagallo S, Diaz-Mochon JJ, Medine CN, Greenhough S, Hannoun Z, Schrader J, Black JR, Fletcher J, Dalgetty D, Thompson AI, Newsome PN, Forbes SJ, Ross JA, Bradley M, Iredale JP. 2011. Unbiased screening of polymer libraries to define novel substrates for functional hepatocytes with inducible drug metabolism. Stem Cell Res. 6(2):92-102.
• Terrace JD, Hay DC, Samuel K, Anderson RA, Currie IS, Parks RW, Forbes SJ, Ross JA. 2010. Portal venous endothelium in developing human liver contains haematopoietic and epithelial progenitor cells. Exp Cell Res. 316(9):1637-47.
• Kung JW, Currie IS, Forbes SJ, Ross JA. 2010. Liver development, regeneration, and carcinogenesis. J Biomed Biotechnol. 2010:984248.
• Sullivan GJ, Hay DC, Park IH, Fletcher J, Hannoun Z, Payne CM, Dalgetty D, Black JR, Ross JA, Samuel K, Wang G, Daley GQ, Lee JH, Church GM, Forbes SJ, Iredale JP, Wilmut I. 2010. Generation of functional human hepatic endoderm from human induced pluripotent stem cells. Hepatology 51(1):329-35.