James Ross is Professor of Liver Cell Biology and director of the Tissue Injury & Repair Group. The group are an integral part of the University of Edinburgh/MRC for Regenerative Medicine and have developed particular expertise in the isolation and functional characterisation of adult and foetal human hepatocytes and both embryonic stem cell-derived and foetal liver stem cell-derived populations including hepatocytes.
Professor Ross has published extensively in the area of liver cell biology, liver involvement in inflammatory processes, cancer and stem cell biology. In recent years he has broadened his interests to include imaging and has developed a novel ultrasound contrast agent for targeted imaging. Current projects involve the extension of this work to other imaging modalities and the development of methods for drug and gene delivery.
Professor Ross is also an active participant in the Centre for Cardiovascular Studies, the Centre for Translational and Chemical Biology and the recently formed Centre for Biomedical Engineering within the University of Edinburgh. The group have active research interests in liver, pancreas, muscle, prostate and eye development and disease.
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 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 for drug discovery or 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.
Approaches and Collaborations
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 other members of the liver theme within MRC-CRM (David Hay, Stuart Forbes, John Iredale), with CRB (Richard Anderson) and with our home department (Surgery - KCH Fearon, SJ Wigmore, I Currie, J Powell, RW Parks and OJ Garden) which hosts the Scottish Liver Transplant Unit.
We also have strong collaborative involvement with the Centre for Cardiovascular Science, with Ian Dransfield in the Centre for inflammation Research and with Rory Duncan in 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.
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
A list of Professor Ross's publications.