|Queensland (Postdoctoral Fellowship)
|USA (Clinical Training Fellowship)
Development of prodrug-activating enzymes for anti-cancer gene therapy.
This project aims to identify and improve enzymes from bacteria that are able to activate non-toxic "prodrugs" into highly toxic anticancer drugs. These enzymes can then be delivered to cancer cells by tumour-specific viruses, making them sensitive to the prodrugs. Normal human cells lack these enzymes, which minimises side-effects in healthy tissue. As well as having the potential to target both dormant and rapidly dividing tumour cells, these particular enzymes will allow us to follow the progression of virus in the body - a vital safety control which has been lacking in previous cancer gene therapy work.
Metabolic Constraints on Tumour Metastasis.
Tumour metastasis is the main cause of mortality in cancer. Our novel finding that metastatic melanoma cells that have no mitochondrial genome, and whose energy metabolism is therefore purely glycolytic, fail to form tumours in the lung, raises the question of whether metabolic flexibility is essential for metastasis. We will investigate this phenomenon in metastatic melanoma and breast carcinoma cells. Manipulating mitochondrial metabolism is a potential therapeutic approach to metastatic cancer.
Understanding the activity of IAP antagonists
Programmed cell death (apoptosis) is required for normal development and disruption of this process is a major factor that leads to tumour development and chemoresistance. ‘Inhibitor of apoptosis' (IAP) proteins regulate cell death and compounds that bind to IAPs are in clinical trials. Instead of blocking the association of two molecules as predicted, these compounds trigger degradation of one protein. Using purified proteins we will determine how drug binding alters protein function. This project will indicate how this promising class of therapeutic molecules functions, and pave the way for development of improved compounds.
Investigating the cell of origin of epithelial ovarian cancer through BRCA1 knockdown.
Mutations in the tumour-suppressor gene BRCA1 specifically increase the risk of both breast and epithelial ovarian cancers. Loss of BRCA1 expression in breast cancer cells increases oestrogen synthesis and reduces response to oestrogen, suggesting a possible causal link for the tissue specificity of cancers in women with BRCA1 mutations. However little is known about these relationships in ovarian cells. This proposal aims to determine if tissue-specific roles exist for BRCA1 in steroidogenesis and oestrogen responsiveness. This will increase our understanding of BRCA1-induced carcinogenesis in breast and ovary and may lead to more specific biomarkers of carcinogenesis in these tissues.
Cancer-causing papillomaviruses: reprogramming of the immune response.
The second biggest cancer killer in women is cancer of the cervix. Cervical cancer is caused by persistent infection of high-risk human papillomavirus (HPV). It is likely that the ability of HPV to cause persistent infection is attributable to immune evasion mechanisms harboured by the virus. The focus of this research is to investigate how HPV reprogrammes the host immune response. Through understanding this, interventions to disrupt these processes can be developed, leading to better treatments for women with pre-cancerous changes resulting from HPV.
Cell line models for aggressive breast cancer growth.
Breast cancer growth is driven by steroid hormone oestrogen and one of the main methods of treating breast cancer, apart from surgery, is to block the action of this hormone, either by blocking its action or by blocking its synthesis. In each case, treated patients often develop tumours that are more aggressive than the original cancer. We have grown breast cancer cells in culture either with tamoxifen to block oestrogen action, or in the absence of oestrogen. Unexpectedly, these treatments both led to more rapidly growing cancers, mimicking the aggressive behaviour in the clinic. We propose to investigate the reasons for this behaviour.
Development of a New Zealand-specific risk assessment tool for melanoma.
This project will develop a risk assessment tool to predict an individual's probability of developing melanoma. It will be specific to New Zealand conditions, and will be simple, non-invasive and cheap enough to be used quickly in primary care. This tool will allow the identification of people at increased risk of developing melanoma so they can be offered an individual programme of melanoma surveillance, tailored to their level of risk, in order to aid prevention, and improve early detection and thus timely treatment of melanoma.
Plasma and serum Vascular Endothelial Growth Factor levels in women with gynaecological cancers and the effect of food compounds.
Vascular endothelial growth factor (VEGF) is a factor that stimulates the growth of blood vessels in malignant tumours. High blood levels have been reported in patients with cancer and therefore proposed as a marker of tumour activity. However, results are varied and complicated by the fact that factors not related to tumours may influence blood VEGF measurement. We wish to investigate the relationship of blood VEGF measurement and tumour behaviour in patients with endometrial and ovarian cancers, by comparing women with and without active cancer. In addition, the effect of food compounds on VEGF levels will be investigated.
To attend the Joint Scientific Meeting of the International Epidemiological Association Western Pacific Region (IEA-WPR) and the Japan Epidemiological Association (JEA) in Japan in January 2010.
To attend the International Society of Nurses in Cancer Care (ISNCC) in Atlanta Georgia. March 2010.
To attend the Trans-Tasman Radiation Oncology Group (TROG) Study Coordinator Workshop and Annual Scientific Meeting 2010, to be held in Queenstown from the 24th March -27th March.
Chemotherapy response in an obese mouse model with colorectal cancer
Colorectal cancer kills over 1200 New Zealanders every year, and obesity is a major risk factor. Obese cancer patients often have a poorer survival than normal weight patients, but it is not known why. This study will test the theory that obesity may lead to less successful chemotherapy treatment. Tumour shrinkage after treatment will be compared between obese and normal weight mice with colorectal cancer. Factors in the blood, liver and tumours of obese mice will be studied to determine if they could interfere with successful chemotherapy treatment.
Purchase of specialist palliative care books, journals and manuals.
Hospice Wanganui continues to receive a Certificate of Accreditation from Quality Health New Zealand; (which is the NZ Council on Healthcare Standards). To continue to achieve these standards of excellence, Hospice Wanganui has reveived a Genesis Oncology grant of $2,693 to cover the cost of the books and manuals that will upgrade and upskill our medical and nursing staff to be able to maintain current and future standards of excellence in palliative / oncology care; education / professional development / cancer research / cancer treatment and relevant new information about palliative/oncology care for our medical doctors and nursing staff.
At Home: A New Zealand documentary exploring the experience of relatives caring for someone dying at home.
The documentary describes the experience of caring for people from a variety of social backgrounds who are dying at home, eg parents caring for an 18 month old child, nurses providing care for a young adult with severe disability, a sister describes the care given to her adult brother at home in the Wairarapa, two daughters describe their mother, an internationally known Maori artist and her death at home in Lower Hutt. Doctors (General practice, Palliative Medicine) and nurses (Palliative Care and District) describe the uniqueness and privilege of supporting patients and families at home. A 50 year old musician and landscape gardener courageously and poignantly describes his hopes as he faces his imminent death. The participation of Keith Quinn (Broadcaster), Jenny Bornholdt (Poet) as well as vox pop with people on the streets of Wellington and some rugby will lighten the reality of these touching stories for a lay audience.
The documentary sensitively explores the courage and love demonstrated by the carers and the support provided by nurses and doctors to facilitate that care at home.The challenging demographics of society with smaller families and increasing life span may put pressure on the ability of the health care system and community to respond to people's wish to die at home. So it is timely that this documentary describes the reality of death at home; a reality full of courage, intimacy and uncertainty. Most people wish to die at home. Yet in the busy pressurized world of today how many of us would have the courage and dedication to care for a relative who wishes to die at home?
Improving a patient's journey through the Radiation Oncology Department
A diagnosis of cancer is distressing for patients. Providing information about procedures and treatment is an effective way to reduce a patient's distress and improve their ability to cope. We seek funding to produce an educational DVD for cancer patients who are to be treated with radiation therapy. Patients will be able to watch this DVD with their friends, family and whanau. The DVD will describe the patient's journey through the radiation therapy department including procedural information on radiation therapy planning and treatment. The DVD will also cover common misconceptions about radiation therapy and provide information on support services available.
Enhancing the training of New Zealand's future Cancer Specialists
A highly successful national NZ Part II teaching program has been in operation since 2005 for trainees in radiation oncology (approximately 8-10 at any time). Funding to date has been tenuous and unpredictable on an annual basis from commercial sponsors. In 2009 the commercial sponsor required increased input into the teaching program, with formal presentation of promotional material. This was considered unacceptable by the organisers (applicants) due to the potential for bias and unethical behaviour. Thus, the national program is at risk of collapse.
Genesis Oncology Trust palliative care breakfast lecture series
For the seventh year the Genesis Oncology Trust with fund the Hospice NZ Breakfast Lecture Series. The aim of this project is to provide a low cost and easily accessible education opportunity for a range of healthcare professionals who have an interest in palliative care. The eleven lecture monthly series is presented via teleconference, making it easily accessible throughout the country. In 2009, 200 people on average listen to the teleconference lecture every month. Thanks to the ongoing support of the Genesis Oncology Trust the lectures are available without charge to registered participants. The primary goal of the 2010 series is to involve more generalists working in the area of palliative care, particularly in rural areas.
Nurse Maude End of Life Online Nursing Education
This project will develop online education for registered nurses on assessment and symptom management in end of life care using an online learning management system. The introduction of the Liverpool Care Pathway (LCP) into aged care facilities has stimulated the need for more palliative care education for nurses. Most nurses receive limited palliative education in their training, so additional education will be vital to the success of the LCP and for improving patient's quality of care. However, there are recognised barriers to accessing face-to-face education (e.g. time, cost, staff shortages) which can be addressed by more flexible, accessible online education.
MicroRNA expression as a biomarker for pancreatic neuroendocrine tumours and adenocarcinomas.
A gene is a set of instructions that tells the cells in our body how to behave. Some genes have instructions that tell cells how to grow, and a mistake (or mutation) might cause abnormal growth, which might result in a cancer. Other factors also control whether a mistake in a gene will cause problems. For example, sometimes a gene with a mistake does not cause any problem because it is "switched off" so that it can't be read. One way that genes can be switched "off" or "on" is by tiny molecules called microRNA's.
This research will look for microRNA's that turn off and on cancers that grow in the pancreas. The two types of cancer in the pancreas are called neuroendocrine tumours and adenocarcinomas. The research aims to understand why these tumours are so hard to treat, when to give treatment, and how we can detect cancer earlier.
The role of germline DNA copy number variation in familial breast cancer risk.
A significant proportion of breast cancers arise in a subset of women who inherit genetic changes that increase risk of developing the disease. However, for most women the changes underlying their disease remain undetermined. Genomic DNA copy number variations (CNVs) are a major source of inherited human genetic variation and to date there have no in depth studies exploring such DNA variations in relation to breast cancer risk. This research aims to explore whether inherited CNVs contribute to increased risk in breast cancer affected families, and thus may ultimately impact on future diagnostic protocols to facilitate improved care in families.
Modulatory effects of phytochemicals and pharmaceutical drugs on ABC transporters and their potential in reversing multidrug resistance in pancreatic and colorectal cancer.
Resistance to chemotherapy has been one of the greatest hurdles towards effective treatment of cancer, and is the main reason for the poor prognosis of diagnosed patients despite the plethora of anticancer compounds currently available. A major mechanism of tumour resistance is the active extrusion of cancer drugs out of tumour cells by proteins called ABC transporters. The aim of this project is to identify natural plant compounds and existing drugs which can stop the action of these transporters and hopefully reverse tumour resistance and improve treatment outcome.