Research Projects
Molecular Signatures Linked to Graft Injury and Tumour Recurrence After Liver Transplantation

Objective and Significance:

Orthotopic liver transplantation (OLT) has been regarded as the best curative treatment for the patients with end stage of liver diseases including advanced liver cirrhosis and acute liver failure. It is also the alternative therapy for the patients with early stage hepatocellular carcinoma (HCC). Because of the severe shortage of grafts from brain-death donors and the importance of timing in the operation for the recipients, living donor liver transplantation (LDLT) may allow early transplantation with its theoretically unlimited source of liver grafts.

Since the first successful adult to adult LDLT in Hong Kong (1994), this surgical innovation has been well established locally and relived the organ donor shortage. However, a liver graft from a living donor is frequently small-for-size for the recipient. On the other hand, to expand the potential liver donor pool, "marginal" liver grafts are often utilized. Grafts are considered marginal if there is an increased risk of initial poor function or primary non-function. Steatosis is the most common reason used to classify a donor liver as marginal. Acute phase fatty graft injury after transplantation will deteriorate when the graft is small-for-size, such as a partial liver graft from a live donor. The acute phase liver grafts injury will not only trigger a series of inflammatory cascades, which subsequently activate cell signaling pathways leading to cell adhesion, migration and invasion, but it will also be the major cause of microvascular barrier dysfunction and disturbance of liver microenvironments. Together with a higher potential ability of liver angiogenesis because of liver regeneration, the small liver graft may also provide a favorable environment for liver tumor growth and metastasis after LDLT for HCC patients.

The precise molecular mechanism of the progression from acute phase liver graft injury, chronic inflammation to late phase tumor recurrence and metastasis will be elucidated in this multidisciplinary collaborative research for liver graft injury during living donor liver transplantation. Understanding of the impact for acute phase liver graft injury on tumor microenvironment will be essential for further development of novel therapies targeting at both acute phase liver graft injury and late phase tumor recurrence. Exploration of the correlation among injury, inflammation and cancer development/progression in this surgical scenario- living donor liver transplantation will be not only important to aim our local excellence, but also contribute to the development of living donor liver transplantation program in the world.

Research Plan and Methodology:

As one part of the CRF project, we aim to study the microRNA profiles associated with acute phase graft injury causing later tumor invasiveness after liver transplantation using small-for-size graft in a rat model. A rat othotopic liver transplantation model has been set up using whole (100%) graft (Group W) and small-for-size (50%) graft (Group S) as donors. The recipients were injected with a rat hepatoma cell line (MH7777, 2xl0 5) via the portal vein after reperfusion. The rats were sacrificed at days I, 3, 14 and 21 after transplantation for histological and molecular analyses. MicroRNA profile of acute phase (day I) between Group W and Group S will be characterized by applying Low Density Array (LDA) analysis. The differential microRNAs were confirmed by real-time RT-PCR. Further functional studies will be carried out by in vitro and in vivo.

Professor K Man, Department of Surgery

Professor Nancy K Man is currently the Director of Liver Transplantation and Liver Cancer Research, and Director of Clinical and Translational Research in Department of Surgery, The University of Hong Kong. She is well-recognized for the advancements of liver transplantation research. Her innovative development and successful application of integrated clinical, translational and basic research for liver graft injury and cancer recurrence after transplantation, has resulted in major advances and impact on transplant oncology and immunology.

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

1. your CV,
2. a brief description of your research interest and experience, and
3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.