B-lymphocytes in Autoimmunity & Malignancies

Professor Fabienne Mackay

Professor, PhD, FAHMS, Director and CEO

The lab studies the immunobiology of B-lymphocytes, particularly the B cell survival factors BAFF and APRIL and their receptors BAFF-R, TACI and BCMA. Professor Mackay has shown that excess BAFF leads to autoimmunity in mice and is associated with human autoimmunity, in particular systemic lupus erythematosus (SLE). This has encouraged the development of Belimumab, a therapeutic BAFF-blocking antibody that has been approved for use in SLE in the clinic. The laboratory’s effort has been extended to understand how dietary interventions lower the risk of developing SLE and how diet/dietary metabolites can be used as therapeutic modalities.

Another research area of the lab is Chronic Lymphocytic Leukaemia (CLL), a blood cancer caused by the clonal expansion of mature B cells. Patients with CLL show severe systemic immunodeficiency that results in death in a quarter of CLL patients despite therapeutic intervention. Our lab has shown that CLL cells rely on BAFF/APRIL to suppress the immune system through IL-10 production. We aim to identify novel therapeutic targets that will be able to restore patient immune function in CLL and halt CLL progression. Hence, the lab is developing a therapeutic antibody against CLL which would not compromise the host’s protective immunity. In an attempt to identify a novel therapeutic target for CLL, we have identified that a fat-rich diet halts CLL progression. We are now investigating the cellular and molecular mechanism underlying this protection against CLL.

CURRENT RESEARCH

  • Developing a novel immune checkpoint inhibitor to treat Chronic Lymphocytic Leukaemia
  • Exploring the role of dietary intervention in modifying the metabolism of cancer cells and promoting anti-cancer immunity
  • Exploring the role of a fibre-rich diet in Systemic Lupus Erythematosus (SLE)
  • Developing novel immunoregulatory protein for the treatment of SLE
  • Studying the role of the chemokine receptor CXCR7 in B cells
  • Investigating the role of BAFF and related signalling molecules in the development and fate of B cells and the pathogenesis of the autoimmune disease
  • Blood cancer
  • Chronic Lymphocytic Leukaemia (CLL)
  • Autoimmune disease
  • Systemic Lupus Erythematosus (SLE)

Staff

  • Arifur Rahman, Autoimmunity Discovery Project
  • Chin Cangmah, Honours Student
  • Chiung-Hsuan Huang, Masters Student
  • Noah Rahman, Visiting Student
  • SiLing Yang, Research Assistant
  • Wing Yu Kwok, Honours Student
  • Yong Sheng, Laboratory Manager
  • Yukli Freedman, Scientific Technical Officer
  • Zihui Li, Honours Student

Internal Collaborators

  • Associate Professor Steven Lane

External Collaborators

  • Associate Professor Margaret Hibbs, Monash University
  • Professor Charles Mackay, Monash University
  • Dr Nicholas Weber, Royal Brisbane and Women’s Hospital

 

  • National Health & Medical Research Council
  • Lupus Research Alliance

STUDENT PROJECTS

Can diet influence immune tolerance?

This project is suitable for an Honours or Masters student. BACKGROUND The Mackay lab has a model of B cell immune tolerance, known as SWHEL. The SWHEL model is a cross between mice with B cells that express a B cell receptor (BCR) specific for the experimental antigen Hen Egg Lysozyme (HEL), and mice that […]

Find Out More

Analysis of the role of BAFF-R in T cell responses

This project is suitable for an Honours or Masters student. BACKGROUND The Mackay lab investigates the immunobiology of B-lymphocytes, particularly the B cell survival factors BAFF and APRIL, and their receptors BAFF-R, TACI and BCMA. The role of BAFF-R signalling in the maintenance of B cells is very well studied. However, even though it has […]

Find Out More

Investigating the role of the chemokine receptor ACKR3 in immune signalling and disease.

This project is suitable for an Honours, Masters or PhD student. BACKGROUND Chemokines are a class of signalling molecules that are important for maintaining homeostatis and the inflammatory responses of cells. Chemokine receptors respond to these molecules by signalling to cells to proliferate or move. In addition to these classical chemokine receptors, there are also […]

Find Out More

Investigating the role of purinergic receptor signalling in the onset and progression of systemic lupus erythematosus

This project is suitable for an Honours, Masters or PhD student. BACKGROUND Many important metabolites that signal via purinergic receptors (molecules in the plasma membrane) are obtained from food or synthesized by the body. BAFF is a B cell survival factor, and the overexpression of BAFF in BAFF-transgenic (BAFF-Tg) mice causes the expansion of autoreactive […]

Find Out More

Discovering novel immunoregulatory molecules underlying the pathogenesis of systemic lupus erythematosus

This project is suitable for an Honours, Masters or PhD student. BACKGROUND Many important metabolites that signal via purinergic receptors (molecules in the plasma membrane) are obtained from food or synthesized by the body. BAFF is a B cell survival factor, and the overexpression of BAFF in BAFF-transgenic (BAFF-Tg) mice causes the expansion of autoreactive […]

Find Out More

Investigating the therapeutic effect of a ketogenic diet in a xenogeneic (PDX) mouse model of chronic lymphocytic leukaemia

This project is suitable for a PhD student or Honours followed by a PhD. BACKGROUND Chronic lymphocytic leukaemia (CLL) is a blood and bone marrow cancer that slowly worsens over time. CLL is one of the most common types of leukemia in adults and typically occurs during or after middle age. Most patients have a […]

Find Out More