Centre for Inflammation Research

Dr Wei-Yu Lu

Wei-Yu Lu's group studies the role of adaptive immune system in modulating liver epithelium regeneration.

Dr Wei-Yu Lu

MRC Career Development Fellow / ESAT Fellow

  • Centre for Inflammation Research

Contact details

Group Members

Postdoctoral Research Fellow - to be hired soon.

Background

Despite having great regenerative capacity, the liver fails to regenerate during chronic liver disease due to impaired hepatocyte proliferation. Currently, there are no specific drugs available to treat chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and liver transplantation remains the only effective treatment for terminal liver failure but limited by the availability of donor organs. It is crucial to understand the process of liver regeneration during chronic liver injury to tackle the epidemic of chronic liver diseases. The understanding of key regulators that promote liver regeneration will lead to new interventions for regenerating damaged liver tissue, thus helping to tackle the global problem of chronic disease. These mechanistic insights also complement ongoing translational studies with aims to provide more efficient methods of regenerative medicine.

My previous studies discovered that bile duct cells called cholangiocytes can become stem cells in the liver and differentiate into hepatocytes, thus revealing novel regenerative pathways and opportunities to promote liver regeneration by modulating the fate of liver stem cells.  During chronic liver injury or extensive hepatocyte damage, compensatory remodelling of bile ducts known as the ductular reaction (DR) occurs. CD4+ lymphocytes infiltrate the liver and predominantly localise to the bile ducts during DR and an imbalance of lymphocyte populations are observed in liver diseases such as NAFLD. We set to investigate the interactions between CD4+ T-cells and cholangiocytes in during liver regeneration.

These studies will provide a better understanding of the role of lymphocytes in affecting epithelial regeneration during chronic liver injury and reveal how lymphocytes interacts with the liver epithelium. In conjunction, these will provide new opportunities of promoting liver regeneration through immunomodulation, combining the research areas of immunology and regenerative medicine.

Research Overview

Immune-epithelial interaction during tissue regeneration

The liver is an organ which can exert cellular plasticity upon injury. When the main regenerative mechanism is impaired, fully differentiated cells can convert into other cell type with different functions as a compensatory regenerative mechanism. During this regenerative process, immune cells such as macrophages and lymphocytes infiltrate the liver in a well-coordinated manner. We use rodent models of liver injury and clinical samples to understanding how T lymphocytes communicate with the epithelium during this regenerative process and the importance of T lymphocytes in maintaining the balance between complete regeneration and tissue repair.

Role of T regulatory cells in Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis (PSC) is a disease affecting the bile ducts, causing obstructive flow of bile into the intestines. PSC is characterised by increased inflammation, scarring and reduced bile duct regeneration. The pathogenesis of PSC is poorly understood but has been suggested to be immune mediated. T regulatory cells (Tregs), a cell type specialized in controlling immune response play an important role in the pathogenesis of autoimmune liver disease such as PSC. We aim to investigate the dynamics and functions of Treg populations during PSC to understand the role of Treg in PSC disease progression and identify targets for potential treatments. We hope the study complement what is currently lacking in human PSC research.

Biographical Profile

Wei-Yu graduated from the University of Edinburgh with a degree in Medical Sciences in 2010. With the gracious support from the Edinburgh University Overseas Research Scholarship and the Charles Darwin Scholarship, he did his PhD training under Prof Stuart Forbes at the Centre for Inflammation Research, University of Edinburgh, where he looked at the possibility of using liver progenitor cells for cellular therapy. Wei-Yu did his postdoctoral training at the Scottish Centre for Regenerative Medicine, where he investigated the plasticity of the biliary epithelium during liver regeneration, and the potential of human liver progenitor cell therapy supported by the United Kingdom Regenerative Medicine Platform (UKRMP). In 2018, Wei-Yu established his own laboratory at the Institute of Immunology and Immunotherapy, University of Birmingham. He then secured a MRC Career Development Award in 2020. He joined the Centre for Inflammation Research, University of Edinburgh in 2021.

Honours and Awards

  • MRC Career Development Award 2021-2025
  • PSC Partners Seeking a Cure Young Investigator Award 2018
  • Birmingham Fellowship 2018
  • Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship 2016 , (awarded but declined)
  • Japan Digestive Disease Week 2015 Best International Presenter

Alumni

  • Dr Naruhiro Kimura (Visiting Research Fellow, Niigata University, Japan)
  • Eleanor Ward (MSc)

Collaborators

  • Professor Stuart Forbes, University of Edinburgh
  • Professor Graham Anderson, University of Birmingham
  • Professor David Withers, University of Birmingham
  • Professor Philip Newsome, University of Birmingham
  • Professor Alicia El-Haj, University of Birmingham
  • Dr Shishir Shetty, University of Birmingham
  • Professor Jagdeep Nanchahal, University of Oxford
  • Professor Sarah Waters, University of Oxford
  • Dr Atsunori Tsuchiya, Niigata University, Japan

Publications

Notch-IGF1 signalling in biliary epithelial cells drives their expansion and inhibits hepatocyte differentiation

22 Jun 2021 In Science Signaling

DOI: 10.1126/scisignal.aay9185

Research output: Contribution to journal › Article › peer-review

 

Expansion, in vivo–ex vivo cycling, and genetic manipulation of primary human hepatocytes

21 Jan 2020 In Proceedings of the National Academy of Sciences, vol 117

DOI: https://www.pnas.org/content/117/3/1678

Research output: Contribution to journal › Article › peer-review

 

Regional differences in human biliary tissues and corresponding in vitro derived organoids

29 Mar 2020 (E-pub ahead of print) In Hepatology

DOI: 10.1002/hep.31252

Research output: Contribution to journal › Article › peer-review

 

Hepatocyte-specific β-catenin deletion during severe liver injury provokes cholangiocytes to differentiate into hepatocytes

29 Jan 2019 In Hepatology, vol 69

DOI: 10.1002/hep.30270

Research output: Contribution to journal › Article › peer-review

 

Mesenchymal stem cells and induced bone marrow‐derived macrophages synergistically improve liver fibrosis in mice

Mar 2019 In Stem Cells Translational Medicine, vol 8

DOI: 10.1002/sctm.18-0105

Research output: Contribution to journal › Article › peer-review

 

More information on publications at Wei-Yu Lu's Research Explorer profile

Funding

Information on funding at Wei-Yu Lu's Research Explorer profile