|Institut Gustave Roussy, France||1|
Cohesin-mediated regulation of RUNX1 in acute myeloid leukaemia.
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 regulation. At least one quarter of AMLs have abnormal cohesin function. Cohesin regulates expression of a gene already well known to cause AML: RUNX1. I hypothesise that cohesin mutations cause AML by leading to abnormal RUNX1 expression. I will test this hypothesis using multiple molecular approaches in leukaemia cells and a zebrafish in vivo model. This research aims to discover how abnormal cohesin causes leukaemia.
Comparative genomic profiling and assessment of DNA repair capacity in sequential tumour samples of patients with ovarian cancer: a study to characterise chemotherapy resistant clones.
Despite advances in medicine, ovarian cancer remains a lethal gynaecological malignancy. Due to its silent nature and lack of adequate screening tools, women usually present with advanced, incurable disease. Although this cancer responds very well to initial chemotherapy, most patients relapse and become resistant to chemotherapy. The mechanisms by which this cancer becomes resistant to chemotherapy are largely unknown. Currently there are few novel targeted therapies available for patients with ovarian cancer. This study aims to identify the mechanisms underlying resistance to chemotherapy and identify novel therapeutic targets, ultimately aiming to improve survival outcomes for these women.
Can stimulation of human antigen presenting cells with TLR ligands improve their capacity to initiate a T-lymphocyte response to a vaccine targeting cancer?
When designing vaccines to treat cancer, we can exploit the body’s own immune system. Sentinel immune cells are specialised immune cells that detect foreign viruses and bacteria, and initiate immune responses to kill them. Sentinel immune cells have special receptors to detect viruses and bacteria; the aim of this research project is to identify molecules that will bind to these receptors and stimulate the sentinel immune cells to initiate an immune response. These molecules can then be included in cancer vaccines so they instruct the patients own sentinel immune cells to stimulate an immune response that will destroy the cancer.
Immunological markers that predict outcome of CIN2
Every year around 1550 women are diagnosed with high-grade pre-malignant cervical cancer in New Zealand. It is now known that in around half of those women disease will resolve without intervention. The purpose of this study is to identify immune markers that predict outcome, so that women who need treatment will be identified, and those whose disease will regress without intervention can be conservatively managed. The outcomes are better diagnosis and reduced over-treatment of women with this common disease.
Biology of megakaryocytic cancers
This project will improve our understanding of blood cancers that affect megakaryocytes (platelet precursors). No specific treatments are available for patients with these disorders, and outcomes are unsatisfactory. Most frequently affected are children with Down syndrome and older people, whose tolerance of chemotherapy is particularly poor. While new therapies are needed for all patients, these two patient groups are especially vulnerable. Our work will interrogate megakaryocytic cancers using modern methods. We will examine mechanisms that lead to disease development and aim to identify new therapy targets. Our tests should help characterise patient cancers and guide development of novel therapies.
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.
To attend the 6th Clinical Epigenetics International Meeting. March 2nd - 4th, 2016, Düsseldorf, Germany.
To undertake Postgraduate Diploma in Medical Science (Palliative Care), University of Auckland
To attend the 11th Palliative Care Congress, (9-11 March 2016) in Glasgow, Scotland.
To complete Dissertation for Masters of Nursing through Auckland University.
To undertake a Master in Social Work at Monash University, Melbourne, Australia.
To attend ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) meeting – 27th-29th April 2016.