Funded projects

The genes of life and death: a role for placental-specific genes in cancer.

The human placenta behaves like cancer. It invades the adjacent uterus, like cancer eroding surrounding organs. Invasive placental cells are similar to cancer cells in their DNA modifications. In fact, DNA modifications in placental cells are more similar to those in cancer cells than to healthy human cells. So, the placenta might hold the key to curing cancer – specifically via retrotransposons: DNA segments that are activated in the placenta and some cancers, but not in healthy organs. We have evidence that these placental genes are activated in cancer, and believe retrotransposons may offer powerful perspectives on cancer prevention and treatment.

Fat and sugar to the rescue – Lipoglycan Cancer Vaccines.

Traditional cancer therapies target malignant tissue directly and cause many toxic side-effects. Cancer Immunotherapy trains the immune system to target cancer tissue. The Ferrier Research Institute’s Dr Gavin Painter and scientists from the Malaghan Institute have reported powerful results using linker-technology to deliver vaccines that will stimulate strong immune reactions against cancer tumours. This new project will develop a library of compounds derived from fat and sugar to feed into the ongoing cancer immunotherapy programme. The result of this complex chemistry will be a simple cure for breast cancer for future generations.

Growth hormone receptor inhibition to improve the efficacy of radiation therapy.

Tumour cell resistance to treatment with radiation is a major clinical challenge in cancer therapy, and agents which improve the efficacy of radiotherapy have the potential to improve treatment outcome in a significant proportion of patients. We have recently demonstrated that inhibiting the actions of growth hormone using a clinically available antagonist, delays the regrowth of endometrial tumours following radiation treatment. We will determine the effectiveness of this drug in reducing tumour growth and improving the effectiveness of radiotherapy in a panel of human tumours, with the aim of improving the clinical management and treatment outcomes.

Targeting ovarian cancer using gold nanoparticles: a novel method to quantify disease, and measure nanoparticles & molecule delivery using MARS spectral CT.

At present, most cancers are staged with imaging, treatment selected, then the patient is re-imaged to see if the treatment is working. We intend to transform that approach by using targeted gold nanoparticles to measure tumour burden as well as drug delivery by using a novel non-invasive imaging technology developed in NZ – MARS spectral CT. Our target is ovarian cancer, but the method can be extended to a wide range of cancers. This approach will allow cancer treatment to be tailored to the individual patient and treatment modified according to identifiable and measurable tumour markers in individual patient.

Whole-genome CRISPR-Cas9 screens for radiosensitivity genes in squamous cell carcinomas of the head and neck.

Radiotherapy is a cornerstone of modern cancer management, yet surprisingly little is known about the factors responsible for radiation sensitivity of tumour cells. In particularly, the genetic factors responsible for differences in intrinsic (cell autonomous) radiosensitivity are poorly understood. This gap in knowledge needs to be filled if choices between cancer therapy options are to be based on the molecular profile of individual tumours. We will utilise a powerful new genetic screening tool called CRISPR-Cas9, recently implemented in our lab, to identify genes that control radiosensitivity of cancers of the head and neck, which are commonly treated with definitive radiotherapy.

Establishing the framework for international comparisons of colorectal cancer management and outcomes – the TRI-PIPER project.

Bowel Cancer is New Zealand’s most common cancer, and one of our most fatal. Our outcomes are worse than in Australia, and we don’t understand why. The care (treatment, quality, timeliness) that patients receive changes how long people live. We have just completed the most comprehensive and detailed examination of bowel cancer care in New Zealand (the PIPER project). This gives us a unique opportunity to compare care between NZ, Australia and UK. We will form an international collaborative network of researchers to identify relevant data sets and data that can be compared between the three countries..

Genesis Oncology Trust palliative care breakfast lecture series.

Now in its 12th year, the Genesis Oncology Trust Lecture Series continues to provide an easily accessible palliative care education opportunity. Delivered via teleconference, the eleven lecture series is attended by approximately 450 people each month. Registered sites throughout the country participate in the series. Participant numbers have steadily increased so that now more than 2600 people have listened to the breakfast lectures to date in 2015. Thanks to the generosity of the Genesis Oncology Trust the lectures will continue to be available without charge to registered participants in 2016.

Studying the contribution of secondary tumor suppressor gene mutations to AML1-ETO driven acute myeloid leukaemia (AML) in a murine bone marrow transplantation model.

Acute myeloid leukaemia (AML) is an aggressive type of blood cancer. This disease is mainly driven by a number of changes (mutations) in the genetic material of certain white blood cells. Several recent studies have identified frequently mutated genes in AML patients, but the actual contribution of these genes to the disease is currently not known. We want to study the impact of these mutations on leukaemia development in a mouse bone marrow transplantation model. This will help us to identify pathways that might be targets for future therapies and thereby might significantly improve patient quality of life and survival.

Targeting tumour hypoxia for precise and personalised treatment of head and neck cancer.

The proposed research focuses on exploiting hypoxia (low oxygen) for treatment of head and neck squamous cell carcinoma (HNSCC). There is compelling clinical evidence suggesting that hypoxia contributes to aggressive disease and failure of ‘standard-of-care' chemo-/radiotherapy in HNSCC. Developing therapeutic strategies to destroy hypoxic tumour cells is therefore a high priority for improving clinical outcomes for HNSCC. Hypoxia-targeting drugs discovered in NZ show great promise for treating this disease. The proposed research aims to characterise determinants of tumour sensitivity to these compounds in order to enable prospective identification of HNSCC patients whose disease is sensitive to hypoxia-targeting drugs.

A tool for risk profiling and accurate prognostication in paediatric glioma integrating clinical features with epigenetics – It is time to move on from the binary classification.

Paediatric glioma is the most common group of brain tumours in children. It comprises a large number of different tumours and it has been difficult to determine individualised treatments for many patients. Cutting edge molecular techniques have revealed new information about these tumours that has not been known before. The difficulty is how to bring these new technologies in the clinic room to decide treatment. This project looks to combine clinical information with information from these new techniques to decide exactly how all this information fits together to form the best treatment for children with glioma.

To attend the 27th Annual Lorne Cancer conference; 12-14th February 2015; Mantra Lorne, Lorne, Victoria, Australia

To undertake two post-graduate papers through Massey University

To attend the 4th International Public Health and Palliative Care Conference, Bristol, UK, May 2015

Exploring a novel target for therapeutic intervention in acute myeloid leukaemia.

AML is a common form of leukaemia and is increasing in frequency due to an ageing population. Cohesin is a protein that functions in cell division and gene regulation16. 13% of AMLs have cohesin mutations2,3. Synthetic lethal approaches hold great potential for cancer treatment by seeking to exploit the ‘Achilles Heel' of cancers, where mutation in a cancer gene sensitises cells to particular drugs. Our research will develop synthetic lethal drugs that target leukaemias with cohesin mutations. The research may lead to personalised medicine for a subset of patients with AML.

Role of SOX2 a stem cell protein in metastatic melanoma.

New Zealand has the highest rate of melanoma in the world and the treatment of metastatic melanoma remains a major challenge. An improved understanding of the molecular mechanisms underlying melanoma pathogenesis would allow the development of more effective therapies. The mechanisms of melanoma invasion are poorly understood. The SOX2 protein has recently been discovered to be expressed in human metastatic melanoma. We seek to investigate how the SOX2 gene is regulated, and to investigate its effects on melanoma behaviour, both in a series of low passage cell lines in culture, and when grown as xenografts in mice.