About the Project
Despite having great regenerative capacity, the liver fails to regenerate during chronic liver disease due to impaired hepatocyte proliferation. Liver disease affects around 2 million people in the UK and 844 million people worldwide and is the only major cause of death that is still increasing compared to other major diseases. Currently, there are no effective treatment against chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and liver transplantation remains the only effective treatment for liver failure but limited by the availability of donor organs. Hence, it is crucial to understand the process of liver regeneration during chronic liver injury to tackle the epidemic of chronic liver diseases.
The liver epithelium is highly plastic in which cellular fate can change in response to severe injury1. The understanding of key regulators that control cell fate changes will discover mechanistic insights which complement ongoing translational studies with aims to provide more efficient methods of regenerative medicine. During chronic liver injury or extensive hepatocyte damage, compensatory remodelling of bile ducts known as the ductular reaction (DR) occurs2. During DR, bile duct cells termed cholangiocytes can become stem cells in the liver and differentiate into hepatocytes3. The understanding of how this process is regulated is crucial for revealing novel regenerative pathways and opportunities to promote liver regeneration by modulating the fate of liver stem cells.
CD4+ lymphocytes infiltrate the liver and predominantly localise to the bile ducts during DR and the imbalance of lymphocyte populations are observed in chronic liver disease6. It is important to understand the interactions between CD4+ T-cells and cholangiocytes, especially its role on liver stem cell differentiation during chronic liver injury. In this project, we will use novel models (in vitro organoids and in vivo transgenic models) to understand the basis of liver regeneration and answer the following key questions. Does the imbalance in lymphocytes ratio during chronic liver injury affect epithelial regeneration and DR? Do some immune cells promote liver regeneration? Can we exploit these regenerative mechanisms and use that for regenerative therapies? Answering these fundamental questions as the aims of this project will establish new approaches to enhance liver regeneration which has the potential to benefit at least 2 million patients in the UK.
Applicants should have a strong background in cell biology and/or immunology. They should have a commitment to research in the field of regenerative medicine and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant biological subject such as Biomedical Sciences.
How to apply
Informal enquiries should be directed to Dr Wei-Yu Lu
Applications should be directed to Dr Wei-Yu Lu (email firstname.lastname@example.org ). To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.
2. Lu, W. Y. et al. Hepatic progenitor cells of biliary origin with liver repopulation capacity. Nat Cell Biol 17, 971-983, doi:10.1038/ncb3203 (2015).
3. Raven, A. et al. Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration. Nature 547, 350-354, doi:10.1038/nature23015 (2017).
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