Professor Samuel Breit
MBBS, MD, FRACP, FRCPA
Prof Breit is a Clinical Immunologist and Immunopathologist at St Vincent’s Hospital Sydney. As a Professor of Medicine at UNSW, he heads the Inflammation and Cytokine Biology Research Program at St Vincent’s Centre of Applied Medical Research. He has a career long interest in biomedical research, has a long track record of project grant support and has published over 160 papers in peer-reviewed journals. Prof Breit’s group has spearheaded the investigation of 2 important molecules his research group first discovered and characterised over a decade ago: the intracellular chloride ion channel protein CLIC1 and the divergent TGF-b superfamily cytokine MIC-1/GDF15. With the latter molecule, through an evolving understanding of its biology and potential clinical application, Prof Breit has then been able to take his basic discoveries, from the bench to the bedside. These discoveries have been licensed to several major international companies where they will be applied to patient diagnosis and therapy: MIC-1/GDF15 diagnostic technology can be used in the diagnosis and management of cancer and cardiovascular disease, whilst therapeutic applications include the treatment of inflammatory diseases, obesity and cancer associated syndromes.
Prof Breit collaborates widely and maintains an active research program, involving post-doctoral scientist and PhD students, directed to understanding the biology, mode of action, disease association and therapeutic application of MIC-1/GDF15 and its receptor GFRAL. Currently his research is focused on understanding the central and peripheral mechanisms by which MIC-1/GDF15 causes anorexia, modulates metabolism and impacts inflammation and immunity
Prof Breit's publications and metrics can be found on https://scholar.google.com/citations?user=ouBIM90AAAAJ&hl=en
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Prof Breit’s seminal studies on the role and pathogenesis of MIC-1/GDF15 in cancer anorexia/cachexia and appetite regulation have been recognised by the NHMRC, by inclusion in the NHMRC Publication “Ten best projects 2011”. The presentation speech describing these findings can be seen on http://youtu.be/iFdGHKnaZnc
Growth differentiation factor 15 (GDF15; also called MIC-1) is a TGFb cytokine, now known to be a distant member of the glial derived neurotrophic factor (GDNF) family that binds to GDNF receptor-a like (GFRAL) and signals through its co-receptor Ret. GFRAL, identified at the GDF15 receptor 2 years ago, is highly localised to the hindbrain area postrema and nucleus of the solitary tract from where most of its anorexic actions and some other metabolic activity derive. Outside of this region and the testis, there is limited if any identified GFRAL expressing. Whilst GDF15 likely primary site of action is known, little is known about the mechanisms underlying its metabolic actions. Further, using robust transgenic animal models GDF15 has bioactivity in a number of different in vivo models including those of chronic inflammation and cancer, whose mechanisms have not been elucidated.
Prof Breit is an international leader in study of GDF15 which his lab first cloned and characterised. Subsequently, his lab has been responsible for elucidation much of the biology of this cytokine, including its most important role as a metabolic regulator.
His lab is currently focussed elucidating the mechanisms by which GDF15 exerts its effects on appetite, metabolism, inflammation and immunity by both direct receptor and indirect non-receptor mediated actions by examining:
i) aspects of the basic biology of the GDF15-GFRAL pathway,
ii) the means by which the GDF15-GFRAL pathway regulates metabolism and
iii) the mechanisms by which the it influences selected immune and inflammatory responses.