Dr. David Brown has an abiding interest in the examination of immune regulation, particularly as it applies to the central nervous system (CNS). Dr Brown’s interest in neuroinflammation was sparked when he noticed that many of his patients with systemic autoimmune disease had significant neurological dysfunction, ranging from depression and personality change to frank neuroinflammatory disease. After his postdoctoral studies at the Salk Institute, USA, Dr Brown returned to Australia to establish his own laboratory at The St Vincent’s Centre for Applied Medical Research. Here using a number of unique models of neurionflammatory disease, he is examining the regulation of the immune system and its interaction with the CNS. Insights that are being gained using these models are applicable to many autoimmune diseases and form a stepping stone to new treatments for these diseases.

Using animal modes related to and including experimental autoimmune encephalomyelitis, and animal model of Multiple Sclerosis, Dr Brown has defined new pathways of immune cell traffic through the brain that are capable of being modified. Modification of these pathways provide an opportunity to change immunity against the brain and treat diseases such as Multiple Sclerosis. In addition to defining how the immune cells interact and travel through the CNS, Dr Brown has an interest in several molecules including macrophage inhibitory cytokine-1 (MIC-1/GDF15) and CCAAT enhancer binding protein delta (CEBPD).

CLIC1 research from Breit Group
CLIC1 is the first cloned human member of the highly conserved CLIC family of intracellular chloride ion channel proteins. Proteins of this family are unusual for ion channels: They are structurally related to the GST omega proteins, are small in size, are readily soluble and have the capacity to move on and off membranes. Whilst CLIC1 has been extensively studied and characterized electrophysiology and high-resolution structures of CLIC1 in its soluble form have been obtained, its biology is poorly understood. However, gene knockout mice have mildly impaired platelet function and its blockade limits inflammatory responses.

MIC-1/GDF15 research from Breit Group
MIC-1/GDF15 is a cytokine and divergent member of the TGF-b superfamily first cloned and characterised by this Group. Its expression is markedly increased in most cells and tissues in response to injury, inflammation or malignancy. As a result, it is frequently overexpressed in many patients with cancer such as those of prostate, breast, colon and pancreas. This overexpression starts early in cancer and can be detected by change in its serum levels. At least early in the course of cancer MIC-1 GDF15 probably helps to limit and control cancer growth and spread. MIC-1/GDF15 expression increases broadly in proportion to the stage and extent of disease and in advancer cancer very high serum levels can lead to anorexia/cachexia, which is mediated by direct actions of this cytokine on appetite regulatory centres in the brain.

As well as Research Program Head at St Vincent’s Centre of Applied Medical Research, Sam Breit is a Clinical Immunologist and Immunopathologist at St Vincent’s Hospital, Sydney and Professor of Medicine at University of New South Wales. The research activities of his Group are centred around the biology, role in disease pathogenesis and clinical application of two molecules that were first cloned and characterised by his laboratory in the 1990’s, on the basis of their increased expression with macrophage activation:

The intracellular chloride ion channel CLIC1.

Current Research Projects

• The role of MIC-1/GDF15 in the biology of cancer
• The mechanism of action of MIC-1/GDF15 in appetite regulation
• The role of MIC-1/GDF15 in chronic inflammatory diseases
• The mechanism of action of CLIC1 in control of chronic inflammatory processes
• Structure/function of CLIC1

Opportunities for PhD and other higher degree research students
Prof Breit has a long track training record in training PhD and other research students. Positions are available for suitably qualified students to undertake laboratory based research within Prof Breit’s group. Such research would be focused around the group’s current project areas and would be negotiated on an individual basis.

Additional top-up funding is also often available for PhD students that already have a basic level of funding from Universities or other funding bodies. For enquiries, please see contact information, below.