I am a molecular geneticist with a special interest in molecular pathology determining the inherited and somatic genetic events that predispose to, and advance cancer development. Much of this work has immediate translatability to clinical genetics practi
Deciphering Tumour Heterogeneity Of Breast Cancer Metastases Using Barcoded Patient Derived Xenografts
Funder
National Health and Medical Research Council
Funding Amount
$583,161.00
Summary
Breast cancer mortality is largely due to metastases that seed from the primary tumour. Breast tumours are known to contain a heterogeneous mix of cells, but the precise way that cells are selected for tumour growth and metastasis (as well as their response to systemic therapy) is not well understood. In this study we will use patient samples and cellular ‘barcoding’ to track the destiny of every single clone throughout disease progression and study the effect of various therapies on metastasis.
Effects Of A Novel Hotspot Mutation Of Brm In Non-Melanoma Skin Cancer Development
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Australia has the highest incidence of skin cancer in the world. SWI/SNF, a yeast nucleosome remodeling complex, is known destabilise interactions in DNA. It is made up of 8-10 proteins, including a novel tumour suppressor Brm. There is some evidence that Brm acts as a tumour suppressor in skin cancer, but relevance of a recently found mutation in Brm is yet to be characterised. This project aims to identify the effect of this mutation, on cellular sensitivity to UV radiation and examine transfo ....Australia has the highest incidence of skin cancer in the world. SWI/SNF, a yeast nucleosome remodeling complex, is known destabilise interactions in DNA. It is made up of 8-10 proteins, including a novel tumour suppressor Brm. There is some evidence that Brm acts as a tumour suppressor in skin cancer, but relevance of a recently found mutation in Brm is yet to be characterised. This project aims to identify the effect of this mutation, on cellular sensitivity to UV radiation and examine transformation to malignancy.Read moreRead less
Identifying Castrate-resistant Tumour Cells In Localised Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$573,047.00
Summary
This proposal addresses one of the most important challenges in cancer: what cell population ‘drives’ tumour progression, and how can it be effectively targeted? We will define the prostate cancer cells that survive androgen withdrawal therapy and investigate new ways to target them. Eliminating these important cells earlier in disease progression will lead to increased survival for men with prostate cancer.
Determining The Clinical Relevance Of Intratumour Heterogeneity In Breast Cancer And Its Relationship To Metastases Formation
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Breast cancer metastasis is generally an incurable disease, yet it is not well-understood. This project aims to understand how cancer metastasises by using a novel and unique approach of analysing multiple regions from matched primary and metastatic tumours from breast cancer patients. Expected outcomes include identifying predictors of treatment resistance and resultant personalised management and therapeutic strategies to improve survival outcomes of breast cancer patients.
Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. With exposure to cancer-causing agents such as cigarette smoke, parts of the lung may suffer permanent damage that increases the risk of lung cancer. Many of these changes include the genes in air passages and lung tissue. A certain change (called methylation) affects some g ....Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. With exposure to cancer-causing agents such as cigarette smoke, parts of the lung may suffer permanent damage that increases the risk of lung cancer. Many of these changes include the genes in air passages and lung tissue. A certain change (called methylation) affects some genes in the lungs, but it is not yet known how common this change is or how it affects smokers and people who have developed lung cancer. We will collect blood and sputum specimens from lung cancer patients to test to see if methylation is present, and also specimens from when patients have a routine bronchoscopy as part of their initial tests. If they have an operation for lung cancer, then the part of the lung that is removed and not needed for diagnosis will also be tested for methylation. In this study, we will study whether methylation is an accurate test for lung cancer, whether it is present in parts of the lung near from the lung cancer, and whether it predicts better or worse results after treatment. We hope that this research study will provide new information about the diagnosis and treatment of lung cancer.Read moreRead less
Epigenetic Changes In The Prostate Cancer Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$848,954.00
Summary
Many men with prostate cancer have slow-growing tumours that are unlikely to spread outside the prostate. These men with low-risk cancer are often monitored to prevent unnecessary aggressive treatments. However, the current methods used to distinguish between slow-growing and aggressive tumours are imprecise and there is a risk of missing aggressive tumours. We aim to identify new biomarkers of prostate cancer by measuring modifications to the DNA in the tumour and surrounding cells
Genetic And Genomic Dissection Of Polycomb Repressive Complex 2 (PRC2) In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$576,598.00
Summary
The evolution of normal cells to cancer involves mutations that activate cancer-causing genes and/or prevent the actions of anti-cancer genes. It has become increasingly evident that cancer development also involves changes to epigenetic regulation, or control of gene activity by chemical modification of the gene or its environment rather that changes in DNA sequence. This project aims to explore the tumour suppressor activity of an important epigenetic regulatory complex in lymphoma.
From Functional Genomics To Precision Medicine: Identifying The Cause And Finding Optimal Therapy For Oral Squamous Cell Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$855,992.00
Summary
There is an alarming increase in mouth cancer in young patients who have never smoked. This is a debilitating and potentially fatal cancer without many treatment options. If the patient survives, the quality of life is usually very poor. Our team of medical, genetic, and mathematics experts are dedicated to finding the cause, and developing new treatments, for young non-smoking patients affected by this devastating cancer.
The Nature And Significance Of Clonal Evolution In Human Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$665,420.00
Summary
Cancers can progress in patients by developing genetic changes that favor the growth, survival and spread of cancer cells. However, the rate at which genetic changes occur in human cancer is not known. This project will determine the degree and biological significance of genetic change in human melanoma by using a novel method of growing tumors from single cells and comparing genetic differences between them.