Dr Andrew Holt
Based: University of Birmingham
Donor: Dame Sheila Sherlock Memorial Fellowship (British Liver Trust and CORE)
Amount: £114,000 (payable over two years)
Start date: 1st July 2003
Title of study: How do stellate cells modify the local immune response of the liver
Download Holt Report CORE 2005.pdf
Dame Sheila Sherlock, who died in December 2001, was acknowledged worldwide as the founder of modern hepatology. She was also instrumental in establishing the British Liver Trust in 1988 and at the time of her death was its President. Dame Sheila was also a Vice President of CORE.
Both charities, recognising her tremendous contribution to hepatology and to their own development, have agreed that the establishment of a Memorial Research Fellowship is a most fitting tribute.
Conclusion to report:
Stromal cells within the liver function to maintain and modify the extracellular matrix in response to changes in environmental conditions. Another feature of these cells is the ability to interact with and modify the behaviour of local inflammatory cells. Liver fibroblasts contribute to the positioning and retention of inflammatory cells within the stroma by supporting adhesion and secreting chemokines and cytokines that provides directional signals for local infiltrating inflammatory cells. Moreover activated HSC can up-regulate recruitment of inflammatory cells through sinusoidal endothelium, maintaining and perpetuating the inflammatory process. Cells recruited to the liver are maintained through interactions with stromal cells, and appear to protected from biological clearance mechanisms such as activation induced cell death. The net result of these processes is to maintain inflammation, preventing clearance of inflammatory cells and modulating a switch from acute resolving to chronic persistent inflammation.