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

  • Dr Md Ashik Ullah, Research Officer/Lab manager
  • Eden Whitlock, Senior Research Assistant
  • Fatemeh Khatami, PhD 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

Discovering novel immunoregulatory molecules underlying the pathogenesis of systemic lupus erythematosus

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). BAFF receptor TACI is highly expressed on memory […]

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