2007 Grant Recipients
$720,476 invested in cancer research projects
Matthew Naylor, Garvan Institute of Medical Research
Supported by Can Too 2006
Role of Elf5 in mammary gland development and neoplasia (Breast
Cancer)
Inappropriate cell differentiation, apoptosis (the appearance of
cells which are dying) and proliferation are hallmarks of cancer.
Elf5 controls proliferation and differentiation during normal
development of the breast and increased expression of Elf5 is
associated with shorter survival in women with breast cancer. We
have developed a transgenic model of inducible Elf5 expression that
will enable us to determine how Elf5 modulates breast development
and induces changes characteristic of cancer. This research will
give us a better understanding of Elf5 function in normal cells and
cancer.
Dr Robert Sutak, Department of Pathology University of
Sydney
Dr Robert Sutak has been awarded the Macquarie Bank
Foundation 2007 Fellowship in cancer research
Molecular mechanisms involved in inhibition of
prostate cancer by targeting the growth and metastasis suppressor
gene, Drg-1, with novel anti-tumour agents.
Recently Drg-1 gene was identified in many cancers which prevents tumour spread and progression. The regulation of Drg-1 expression and its biological role(s) remain. It has been demonstrated that Drg-1 is regulated by intracellular Fe (iron) and that novel Fe chelators (which remove iron from tissues) markedly and selectively inhibit tumour growth in vivo and up-regulate Drg-1. The regulation and role of Drg-1 in tumours will be examined, and this may lead to novel therapies.
Dr Nicole Verrills, University of Newcastle
Supported by Newcastle Frangipani Committee
2006
The role of protein phosphatase 2A in breast cancer
Breast cancer, the leading cause of cancer-associated death in women, results from altered cancer causing genes (oncogenes and tumour suppressor genes). Investigation of oncogenes, and their cellular signalling pathways, has resulted in novel therapies. However clinical trials show that targeting a single pathway is not sufficient for effective therapy. This project will investigate the tumour suppressor gene, PP2A, in breast cancer and will highlight the crucial signalling pathways involved, thereby identifying novel targets for new treatments of breast cancer.
Dr Kirsten Hammond, University of Sydney
Supported by Can Too 2006
The role of complement in ultraviolet A radiation-induced immunosuppression (Skin Cancer)
Skin cancer is caused by ultraviolet (UV) radiation in sunlight. UV is a potent carcinogen (cancer causing agent) because it causes cells to become cancerous while simultaneously preventing the immune system from destroying them. Ultraviolet light is made up of two spectra: UVA and UVB. This study investigates a new mechanism whereby UVA causes immune suppression. Understanding how this process occurs is critical to preventing it.
Dr Tao Liu, Children’s Cancer Institute Australia
Supported by Can Too 2006
The role of class 111 histone deacetylase SIRT1 in neuroblastoma (Childrens Cancer)
Cancer is the second most common cause of childhood death. Neuroblastoma is the most common solid tumour of early childhood. We aim to investigate how a gene called SIRT1 contributes to neuroblastoma initiation and whether combination therapy with an inhibitor of SIRT1 and chemotherapy exerts synergistic anti-cancer effects. The results from this study will provide better understanding of neuroblastoma initiation and the basis for clinical trials of the combination therapy.
Dr Munif Allanson, University of Sydney
Supported by Blackmores Three Island Race 2006
The protective role of elevated cutaneous cyclic guanosine monophosphate against (cGMP) skin cancer development in the emouse (Skin Cancer)
We have reported that the UVA waveband of solar UV radiation has immunoprotective effects against the UVB waveband, and therefore may inhibit the promotion of UVB-initiated skin carcinogenesis. UVA protection is via haem oxygenase upregulation, the production of carbon monoxide, and the elevation of cutaneous cGMP. We aim to demonstrate that elevation pharmacologically of cutaneous cGMP, by activation of its synthesis or inhibition of its degradation, reduces photocarcinogenesis, or growth of transplanted skin cancer cells in the mouse.
Dr Graham Ball, University of New South Wales - New drug
design
Supported by Can Too 2006Structural studies of the DNA complexes of novel antitumour agents to aid better drug design (Drug Design)
Many drugs kill tumours by binding to DNA. A new group of DNA-binding drugs is emerging with good experimental antitumour activity that works by preventing cells from expressing their genes. We do not understand the details of the structure of these DNA-drug complexes, nor how they inhibit gene expression. In this work we are proposing to study the 3-dimensional structure of such complexes in solution by NMR spectroscopy (magnetic resonance), so as to aid better drug design in the future.
Dr Megan Fabbro, Children’s Medical Research Institute
Supported by Can Too 2006
Regulation of cytokinesis by EPLIN, and actin-binding protein (Understanding Cell Division)
Cell division maintains the stability and integrity of our genome. Genomic instability can lead to cancer. Cytokinesis is the final stage of cell division and is a critical step in protecting genomic integrity. It involves segregating the genome, cleaving the cell membrane and generating two independent daughter cells. We identified EPLIN as a new component of this process and it appears to function in cytokinesis. Therefore, our aim is to characterise the mechanisms of action of EPLIN in the final stages of cell division. We will determine which EPLIN part connects it to cytokinesis, how its activity is controlled and will test its role to recruit other proteins to the correct location inside cells to drive cytokinesis.
Dr Xiao Jane Huang, University of Sydney
Supported by MasterCard and the Young Cure Cancer Committee
Carnivale 2006
Lack of expression of hOGG1 in basal layer of epidermis predisposes to UVA-induced skin carcinogenesis in humans (Skin Cancer)
Traditionally UVB was thought to be the dominant carcinogen in sunlight. However, more and more evidence suggests that UVA has approximately equal contributions to development of cancer. In this project, we will investigate the roles of DNA repair enzyme hOGG1 in inhibition of UV-induced p53 mutation which is an early event in skin carcinogenesis.
Dr Xu Dong Zhang, Newcastle Mater Misericordiae Hospital
Supported by 2006 Christmas Card sales
Characterization of p53 Isoforms in Human Melanoma: Do They Play a Role in Chemoresistance? (Skin Cancer)
Unresponsiveness of melanoma to chemotherapy is often due to its resistance to killing mediated by a tumor-suppressing protein called p53. This is predominantly expressed as smaller forms than in normal cells, and is functionally inactive in melanoma cells. We hypothesize that the smaller forms of p53 are incapable of killing and may inhibit the tumor-killing function of normal p53. We will test this idea and delineate the underlying mechanism(s) in order to identify new molecular targets for treatment of melanoma.
