More than NZ$2 million has been awarded by the Health Research Council of New Zealand (HRC) and the Agency for Science, Technology and Research (A*STAR, Singapore) to support research into cancer through a joint research initiative. The initiativesupports applicants to engage in research activities that will produce gains for New Zealand and Singapore, and offer significant leverage to build New Zealand’s health research capacity.
The joint fund was open to proposals from New Zealand and Singapore-based public research organisations, including universities and institutes supported by the HRC and A*STAR. In New Zealand, the fund was also open to companies doing research including Crown Research Institutes, research associations and private companies.
The partnership is part of the HRC’s work on the development of international funding partnerships with other countries to facilitate research programmes of joint interest.
Details of funding offered to the research team in the HRC/A*STAR joint initiative are as follows:
YB-1 interacting partners in breast cancer progression
Principal Investigators: Professor Antony Braithwaite(University of Otago) and Professor BoonHuat Bay (NationalUniversity of Singapore)
Project summary: Y-box binding protein 1 (YB-1) is commonly elevated in many human cancers. The cancer-promoting properties of YB-1 are associated with increased resistance to drugs, tumour growth and poor patient outcome. Control of these processes takes place in the nucleus. The precise molecular nature of the active cancer-promoting subtype of YB-1 present in the nucleus is unknown. Identification of this species will provide the basis for a specific and highly prognostic indicator. This proposal, which builds on our recently published analyses of endogenous YB-1, aims to identify the molecular nature of this cancer-promoting subtype of YB-1 and to determine how it functions. From this knowledge we will develop an antibody that specifically recognises only the nuclear YB-1 species and establish this species as a prognostic indicator for human cancers.
Oestrogen-dependent regulation of gene expression by cohesin in breast cancer
Principal Investigators: Dr Julia Horsfield(University of Otago) and Dr Yijun Ruan(Genome Institute of Singapore)
Project summary: Breast cancer is one of the most common cancers in women worldwide. About 70% of breast cancers are positive for oestrogen receptor alpha (ER) and are dependent on oestrogen for proliferation. ER-positive breast cancers are treated with anti-oestrogens such as tamoxifen, but resistance to anti-oestrogens is common. Understanding the action of oestrogen is essential for developing new therapies. Cohesin is a multi-unit protein involved in both cell division and gene expression. Importantly, cohesin colocalizes with ERon chromosomes, and controls expression of the oestrogen-responsive cancer-causing gene, c-MYC. Since c-MYC overexpression causes resistance to anti-oestrogen therapy, targeting cohesin could overcome endocrine resistance in breast cancer.We will determine how cohesin contributes to genome organization by ERand identify specific cancer-causing genes that are regulated by both ERand cohesin. We will focus on c-MYC in particular. We expect to identify new pathways for future therapy in ER–positivebreast cancers.
Molecular diagnostic test for the prediction of survival and drug response in ovarian cancer
Principal Investigators: Associate Professor Parry Guilford(University of Otago) and Professor Jean Paul Thiery(Institute of Molecular and Cell Biology, A*STAR)
Project summary: Ovarian cancer is a devastating disease with dismal survival rates. The main method of treatment uses platinum-based drugs in addition to surgery. These drugs are well tolerated by patients and have an initial response rate of over 70%. However, most patients eventually develop resistance to the drugs and succumb to the disease. We believe that resistance to these drugs is induced by a phenomena called the epithelial-mesenchymal transition (EMT). EMT results in cells becoming more mobile and resistant to cell death. We propose to develop a test to quantify the EMT in samples from ovarian cancer patients. This test will be able to be used to predict which patients are likely to benefit from platinum drug treatment, preventing the under or over-treatment of patients. Moreover, the test would be an important aid in the on-going development of drugs that aim to reverse the EMT and resensitise patients to platinum therapy.
Epigenomics of liver tumour induction and progression: use of a zebrafish model
Principal Investigators: Professor Ian Morison(University of Otago) and Dr Sinnakaruppan Mathavan(Genome Institute of Singapore)
Project summary: Global epidemiology of liver cancer reveals a high prevalence in South-east Asia, Australia and New Zealand. Molecular changes in liver tumour can be studied using human tumour samples or cancer cell lines. However, to study the molecular mechanisms of the induction and progression of the disease, there is a need for a vertebrate model. Zebrafish has been shown to be an ideal model for this approach. We have established zebrafish lines that can produce liver tumours by oncogene transgenics or carcinogens. Using these lines, we can monitor the induction and progression of tumours and analyse the molecular changes during their progression. We will use this model to analyse epigenetic changes (DNA methylation and histone modifications) by using established techniques (ChIP-sequencing and genome-wide bisulphite methylation sequencing). This project will help us to understand the mechanisms of liver tumour leading to the development of molecular markers and therapeutics for the disease.