The Cancer Biology Research Group
The Cancer Biology Research Group, which is headed by Assoc Prof Graham Baldwin, focuses on the mechanisms by which peptide growth factors stimulate proliferation in the normal gastrointestinal mucosa and development of gastrointestinal cancers. At present we are concentrating on precursors of the peptide hormone gastrin, with the long term goal of developing new therapies for colorectal carcinoma (CRC).
The gastrin field has been revolutionised in the past decade by the discovery that non-amidated gastrins (NAGs) have a completely different spectrum of biological activities from mature amidated gastrin (2). Studies from several laboratories including our own have shown that, as well as stimulating the proliferation and migration of a variety of cell lines in vitro (2), NAGs promote proliferation of the colonic mucosa, and accelerate CRC development in vivo. Clinical studies have shown that CRC produce NAGs, that circulating concentrations of NAGs are increased in patients with CRC, and that a circulating gastrin concentration above normal was associated with a 3.9-fold greater risk of developing CRC. Despite the potential importance of these discoveries it is not clear which are the bioactive NAGs, or what is the structure of the receptor(s) responsible.
We recently demonstrated that gastrins selectively bind two Fe3+ ions with high affinity, and that binding of Fe3+ ions is essential for the biological activity of NAGs. These observations stimulated a reappraisal of the role of gastrins in metal ion homeostasis, which led to our unexpected observations that circulating gastrin is increased in animals and humans with iron overload (11), and that genetic manipulation of gastrin expression in mice resulted in reciprocal changes in iron homeostasis (19).
The laboratory is funded through multiple NHMRC Project Grants, through the Austin Hospital Medical Research Foundation, and through a NIH (USA) Project Grant “The Biology of Gastrin-Ferric Ion Complexes” held by Principal Investigator Graham Baldwin with Chief Investigators Prof. Shulkes, Assoc. Prof. Greg Anderson (Queensland Institute for Medical Research), Prof. Ray Norton (the Walter and Eliza Hall Institute) and Prof. Ted Baker (University of Auckland).
Research Staff
top of page- Head: Associate Professor Graham Baldwin
Tel: +613 9496 5592
Email: grahamsb@unimelb.edu.au - Dr Hong He (Senior Research Officer)
- Dr Suzana Kovac (Research Officer)
- Chelsea Dumesny (Research Assistant)
- Nhi Huynh (Research Assistant)
Higher Degree Students
top of page- Gianni Bramante (PhD, 2007 – 2010): Growth Factors and Gastrointestinal Cancer.
- Kevin Liu (PhD, 2009 – 2011): Interaction between p21-activated Kinase (PAK1) and b-catenin in Colorectal Cancer.
Honours Students
top of page- Lin Xiao (2009): Induction of Peptide Hormones and their Receptors by Hypoxia in Human Carcinoma Cells.
Graduating Students
top of pageResearch Higher Degree and Undergraduate Degree graduating students are listed on the graduating students page.
Publications
top of pageResearch Publications from 2003 onwards are available on the Research Publications page.
Funding
top of pageDetails of research funding from 2003 onwards is available from the Research Funding page.