James Ross was director of the Tissue Injury & Repair Group within the Department of Surgery. The group develped particular expertise in the isolation and functional characterisation of adult and foetal human hepatocytes and both embryonic stem cell-derived and induced pluripotent cell-derived hepatocytes. The group participated in the StemBANCC European consortium and led the iPSC models in Drug Safety work package.
Professor Ross has published extensively in the area of liver cell biology, liver involvement in inflammatory processes, cancer and stem cell biology. The group’s interests also included the production of hybridomas and the development of novel lipid-based ultrasound contrast agents for targeted imaging and for drug and gene delivery.
Professor Ross contributed to the inception of the Centre for Regenerative Medicine was also an active participant in the Centre for Cardiovascular Studies, the Centre for Translational and Chemical Biology and the nascent Centre for Biomedical Engineering within the University of Edinburgh. The group were active in liver, pancreas, muscle, prostate and eye development and disease processes.
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 hepatocytes and fetal, embryonic, or induced pluripotent, stem cell-derived hepatocytes is valuable in ascertaining how closely in vitro differentiation mimics the in vivo situation. In addition, such information provides 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 for drug discovery or toxicology.
We developed expertise in examining human hepatocyte function and differentiation from fetal stem cells, through fetal hepatocytes to adult hepatocytes and also collaborated on the differentiation of human ES cells to hepatocytes. The group developed methods for bulk culture of definitive endoderm from human iPS cells for differentiation to functional hepatocytes. The group were part of the StemBANCC consortium (www.stembancc.org) leading the work package developing iPSC models for Drug Safety.
Studies included examining 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 included 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 also investigated the contribution of the liver to the systemic inflammatory response in cancer and cardiovascular disease. A particular interest was 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.
Approaches and Collaborations
We utilised a combination of primary human cells and cell lines, human ES cells and iPS cells to examine the differentiation and function of adult and progenitor liver cells. Cell function and cell fate were analysed using molecular, biochemical and proteomic techniques.
There were strong collaborative links with other members of the liver theme within MRC-Centre for Regenerative Medicine, with the MRC Centre for Reproductive Health and with members of our home Department of Surgery which hosts the Scottish Liver Transplant Unit.
Strong collaborative involvement with the Centre for Cardiovascular Science and the Centre for inflammation Research led to key publications in apoptosis research and in the design and manufacture of lipid-encapsulated contrast microbubbles which, by incorporating specific ligands into the surface of the microbubbles, can be targeted to specific cellular and tissue sites within the vasculature.
Sources of Funding
- Medical Research Council (MRC)
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Engineering and Physical Sciences Research Council (EPSRC)
- British Heart Foundation
- Wellcome Trust
- Association of International Cancer Research (AICR)
- Leverhulme Trust
- Cancer Research UK
- Royal College of Surgeons of Edinburgh
- EU Framework Programme 6
- Prostate Cancer UK
- Chief Scientist Office
- Wyeth Translational Award
- Daphne Jackson Trust
- Dr. Hadwen Trust
- IMI StemBANCC project
A list of Professor Ross's publications can be found in the below pdf.