I am a molecular biologist with research interests in cancer genetics, neurodegenerative disorders and development of novel therapeutics. My major focus is on the cellular response to different stresses and the consequences thereof.
Role Of Mouse Rad21 And Rec8 Genes In Recombination And Ionising Radiation Response
Funder
National Health and Medical Research Council
Funding Amount
$403,750.00
Summary
We have created a line of mice and are creating a second mouse line which lack two specific genes known as Mrec8 and Mrad21. These genes have a number of roles in mammals. These roles include acting as a glue to hold chromosomes together and allowing exchange of DNA between separate DNA molecules. The latter is important in physiological processes such as genetic exchange during meiosis, but also in the response of the cell to DNA damage, specifically, breakages in both strands of the DNA helix. ....We have created a line of mice and are creating a second mouse line which lack two specific genes known as Mrec8 and Mrad21. These genes have a number of roles in mammals. These roles include acting as a glue to hold chromosomes together and allowing exchange of DNA between separate DNA molecules. The latter is important in physiological processes such as genetic exchange during meiosis, but also in the response of the cell to DNA damage, specifically, breakages in both strands of the DNA helix. In the studies proposed here, we will breed these mice both with each other and with other mice that have specific, single gene defects which lead to abnormal responses to DNA strand breakages. We shall assess the effects of the different genes on response to DNA strand breaking agents in the animals, as well as in cells which have been derived from the animals. These experiments are expected to shed light onto the consequences of defects in DNA repair for the stability of cells and animals, and may provide information which ultimately benefits cancer patients, especially those having radiotherapy.Read moreRead less
Therapeutic Targeting Of Precancerous Stem Cells In T Cell Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$674,737.00
Summary
We have recently identified a stem cell population causes T cell leukaemia. These cells may also survive conventional leukaemia therapies and cause relapse. This project will determine whether these stem cells can be killed using conventional leukaemia therapeutics. In addition, we will identify new therapeutic targets to eliminate these cells. This will enable us to specifically target the cells responsible for leukaemia relapse.
Determining The Tumour Suppressor Function Of The MCC Gene And Its Significance To Treatment Outcomes In Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
This project analyses the early stages of bowel cancer, where we have discovered a new gene defect. We want to determine how the MCC gene defect promotes tumorigenesis and how it affects treatment outcomes, by studying a novel mouse model of bowel cancer. This will determine which cellular functions are altered following loss of MCC in bowel tumours and if the MCC defect can be exploited to identify patients who would benefit from radiotherapy or specific chemotherapies.
Prediction Of Clinical Radiosensitivity Caused By Ionising Radiation During Radiotherapy.
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
Around one to five percent of cancer patients suffer from significant side effects in normal tissue exposed to ionizing radiation during radiotherapy. Although radiotherapy is an effective therapy for cancer treatment, the amount of radiation is generally restricted to minimize the incidence of these severe side effects (radiosensitivity). This means that individuals who don't have radiosensitivity are not getting the dose of radiation that would be most beneficial. A major goal of radiation bio ....Around one to five percent of cancer patients suffer from significant side effects in normal tissue exposed to ionizing radiation during radiotherapy. Although radiotherapy is an effective therapy for cancer treatment, the amount of radiation is generally restricted to minimize the incidence of these severe side effects (radiosensitivity). This means that individuals who don't have radiosensitivity are not getting the dose of radiation that would be most beneficial. A major goal of radiation biology research is to develop efficient predictive measures that could identify radiosensitive individuals prior to treatment. This predictive ability would enable the individualisation of radiotherapy radiation doses, which should result in improvement of tumour control rates and a reduction in the incidence of side effects associated with radiotherapy. We aim to understand radiosensitivity at the molecular level using the powerful technology of microarrays. Using microarray technology, thousands of genes can be tested for expression activity simultaneously. We have a unique tissue bank established from many radiosensitive and non-sensitive control radiotherapy patients. The use of microarray technology on samples from this unique tissue bank may enable the gene expression pattern of individuals that display radiosensitivity to be distinguished from the rest of the population. In conjunction, two additional tests will be used to determine who is susceptible to radiosensitive reactions which include assessment of a DNA repair pathway and assessment of the length of the telomeres (Caps on the ends of the chromosomes), both of which have been shown to be involved with radiosensitivy. This experimentation will hopefully lead to the development of a predictive assay for use in the clinic for cancer patients prior to receiving radiotherapy.Read moreRead less
This proposal will focus on determining the effect that disruption of molecules involved in repairing DNA has on development of adverse reactions following cancer radiation treatment. Radiation is efective for cancer but tissues that reside next to the tumour are also exposed to radiation (which can damage DNA) during radiotherapy. About 1-5% of radiotherapy patients develop unexpectedly severe side effects in their normal tissues. The dose of radiation used for treatment to the rest of patients ....This proposal will focus on determining the effect that disruption of molecules involved in repairing DNA has on development of adverse reactions following cancer radiation treatment. Radiation is efective for cancer but tissues that reside next to the tumour are also exposed to radiation (which can damage DNA) during radiotherapy. About 1-5% of radiotherapy patients develop unexpectedly severe side effects in their normal tissues. The dose of radiation used for treatment to the rest of patients (>95%) is restrained to assure only a small proportion risk developing severe reactions. If one could predict which individuals were more susceptible to these reactions, then their large dose could be lowered to avoid the problem, and importantly, the dose could be increased for the majority of the patients, which would lead to a higher cancer cure rate. There are over 130 genes involved in repairing DNA. We hypothesize that dysfunctional DNA repair molecules are likely candidates to cause radiosensitivity in these individuals. In fact, a few of these genes have already been found to cause radiosensitivity, but we aim to assess all of the DNA repair genes in samples from patients that have had severe reactions to radiotherapy. Here we will use biospecimens, unique to our study and obtained from clinically radiosensitive cancer patients. We will use very sensitive, state-of-the-art procedures to test RNA and protein levels in our patients' cells and the latest technology to test what happens when candidate DNA repair molecule levels are altered. Additionally, we will determine the changes in DNA repair molecule numbers in response to different doses of radiation. We anticipate that results from these experiments will lead to the development of a clinical assay to test the likelihood of an individual having a severe reaction to radiotherapy, thus allowing individualization of treatment and, reducing radiotherapy side effects ultimately increasing cancer cure rates.Read moreRead less