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Professor Stuart Forbes
Professor of Transplantation and Regenerative Medicine; Associate Director; Theme leader Liver Stem Cell Biology and Tissue Repair; Consultant Hepatologist Scottish Liver Transplant Unit
Type of staff member: Associated Principal Investigator
Research Theme: Tissue Remodelling and Regeneration
Qualifications: MB ChB, BSc (Hons) University of Edinburgh 1986-92 PhD, Imperial College London 2000 FRCP (Edin), Royal College of Physician of Edinburgh 2009
Alexander Raven (PhD student)
Alexander Raven (PhD student)
Davina Wojtacha (Senior research assistant)
Janet Man (Senior research assistant)
Philip Starkey Lewis (Postdoc)
Sarah Minnis-Lyon (Clinical research fellow)
Sofia Ferrera Gonzalez (PhD student)
Wei-Yu Lu (Research fellow)
Eoghan O'Duibhir (Postdoc)
Jennifer Cusiter (UKRMP Niche hub project manager)
Marieke Hoeve (UKRMP Niche hub project manager (maternity cover))
Andrew Bond (Postdoc)
Benjamin Dwyer (Postdoc)
Liver disease is the 5th commonest cause of death in the UK and the deaths from cirrhosis are rapidly rising. Currently the only curative option for end-stage liver disease is liver transplantation. Donor organ availability cannot even meet current demand and many patients die whilst waiting for a suitable organ. Alternative therapeutic strategies are urgently required for the treatment of advanced liver disease.
The normal liver regenerates through division of mature hepatocytes. However, in chronic liver injury this capacity is lost. Fortunately we have a second tier of cells that can regenerate the liver- the Hepatic Progenitor Cells (HPCs or oval cells). These bipotential progenitor cells can give rise to both hepatocytes and biliary epithelium but may also be a potential source of liver cancer.
Image shows liver progenitor cells (red) in their niche (green). Image credit Dr Luke Boulter.
Approaches and progress
Our program of research concentrates on understanding how the Hepatic Progenitor Cells regenerate the liver in chronic disease and how this process becomes deranged in the development of liver cancer. By understanding what controls this process we aim to be able to promote healthy liver regeneration and reduce the formation of liver cirrhosis and cancer.
We are also developing pre-clinical and clinical tools to stimulate liver regeneration and reduce scarring using cell therapy. In particular we have found that bone marrow derived macrophages can promote liver regneration and reduce scarring and this is being developed as a clinical therapy (funded by the Medical Research Council). We have a clinical research program of “stem cell therapy for cirrhosis” funded by the Jules Thorn Trust and Scottish Enterprise.
Image shows liver cells (red with nuclei in blue) in the early damaged liver with liver stem cells in green migrating to the damaged areas. In the healthy liver, the liver stem cells are only found surrounding the bile ducts close to the blood vessels (black area, on right with some red blood cells in orange). Image credit Dr Luke Boulter.
WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J Clin Invest. 2015 ;125(3):1269-85. .
Hepatic progenitor cells of biliary origin with liver repopulation capacity. Nat Cell Biol. 2015 ;17(8):971-83. .
Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling. Proc Natl Acad Sci U S A. 2013 ;110(16):6542-7. .
Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nat Med. 2012 ;18(4):572-9. .
Sources of Funding Held Within CIR:
Principal Grant Holder:
Grant Coapplicants:Grant value: £3,600,000
Medical Research Council BMC MAC (MR/M007588/1)
Principal Grant Holder:Grant value: £1,957,180
Medical Research Council
This page was last modified on 21 September, 2015