Cancer Biology Research Group
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Professor Graham Baldwin+61 3 9496 5592
Research Overview
The development of many cancers is controlled by growth factors. Our research has focused on the role of precursors of the peptide hormone gastrin as growth factors in colon cancer. With funding from the NHMRC and the US National Institutes of Health we have demonstrated that the biological activity of gastrin precursors is absolutely dependent on the presence of ferric ions. We are now exploring the therapeutic implications of this discovery in human colon cancer cell lines in vitro, in animal models, and in human tumours.
During our studies of the interactions between gastrin and metal ions we made the surprising discovery that zinc ions upregulate gastrin expression by as much as 50-fold. This finding led us into a more detailed exploration of the intracellular consequences of treatment with zinc ions. We have now shown that zinc ions reduce the deleterious effects of oxygen deprivation in human kidney cell lines and during renal surgery in rat and sheep animal models. This observation has the potential to result in significant improvements in the outcomes of human renal surgeries, including partial nephrectomy (PN) for kidney cancer and renal transplantation.
Growth factor signalling is critically dependent on kinase cascades, and our research focuses on the p21-activated kinase (PAK) family. We have shown, using selective PAK inhibitors and shRNA knockdown in human cell lines in vitro and in animal models, that PAK1 plays a crucial role in the development of colorectal cancer. We are currently extending this research into pancreatic cancer.
Staff
- Professor Graham Baldwin, Group Head
- Dr. Mehrdad Nikfarjam, Surgeon
- Dr. Joseph Ischia, Surgeon
- Dr. Hong He, Senior Research Fellow
- Dr. Oneel Patel, Research Fellow
- Dr. Kate Marshall, Research Fellow
- Chelsea Dumesny, Research Assistant
- Nhi Huynh, Research Assistant
- Marie Laval, Research Assistant
- Dannel Yeo, Ph. D. student
- Kai Wang, Ph. D. student
Collaborators
Professor Damien Bolton, Department of Urology, Austin Health.
Funding
- NHMRC
- Pancare Foundation
- Austin Medical Research Foundation
Research Outcomes
Ranasinghe, W.K., Xiao, L., Kovac, S., Chang, M., Michiels, C., Bolton, D., Shulkes, A., Baldwin, G.S. and Patel, O. (2013) The role of hypoxia-inducible factor 1alpha in determining the properties of castrate-resistant prostate cancers. PLoS ONE 8(1): e54251.
Westwood, D.A., Patel, O. and Baldwin, G.S. (2014) Gastrin mediates resistance to hypoxia-induced cell death in xenografts of the human colorectal cancer cell line LoVo. Biochim. Biophys. Acta. Molecular Cell Research. 1843: 2471-2480.
Yeo, D., Huynh, N., Beutler, J.A., Christophi, C., Shulkes, A., Baldwin, G.S., Nikfarjam, M. and He, H. (2014) Glaucarubinone and gemcitabine synergistically reduce pancreatic cancer growth via down-regulation of p21-activated kinases. Cancer Letters. 346: 264-272.
Laval, M., Baldwin, G.S., Shulkes, A. and Marshall, K.M. (2015) Increased gastrin gene expression provides a physiological advantage to mice under hypoxic conditions. Am. J. Physiol. Gastrointestinal and Liver Physiology. 308: G76-84.
Research Publications
Xiao, L., Kovac, S., Chang, M., Shulkes, A., Baldwin, G.S. and Patel, O. (2014) Zinc ions upregulate the hormone gastrin via an E-box motif in the proximal gastrin promoter. J. Molecular Endocrinol. 52: 29-42.
Baldwin, G.S., George, G.N. and Pushie, J. (2015) High Affinity Binding of Indium and Ruthenium Ions by Gastrins. PLoS One. 10: e0140126.
Yeo, D., He, H., Patel, O., Baldwin, G.S., Lowy, A.M. and Nikfarjam, M. (2016) FRAX597, a PAK1 Inhibitor, Synergistically Reduces Pancreatic Cancer Growth when Combined with Gemcitabine. BMC Cancer. 16: 24-35.