I lead a research program to improve outcomes for patients with chronic myeloid leukaemia (CML). We aim to identify poor risk patients and test new treatment strategies to reduce adverse outcomes. In good risk patients we aim to reduce the need for lifelong drug dependency. Through a combination of clinical trials, innovative correlative studies, and strong scientific collaborations, my team will continue to improve outcomes for CML patients globally.
Characterisation Of A New Poor-Risk Sub-Category Of Chronic Phase Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$609,320.00
Summary
The introduction of targeted therapy for chronic myeloid leukaemia (CML) has resulted in excellent responses for many patients. However, some 30-40% of patients respond very poorly to this therapy and therapeutic advances are urgently needed to improve response in these patients. In order to better treat these poor risk patients we aim, in this project, to develop a greater understanding of their disease, and from this identify specific cellular targets for future drug treatment/combination ther ....The introduction of targeted therapy for chronic myeloid leukaemia (CML) has resulted in excellent responses for many patients. However, some 30-40% of patients respond very poorly to this therapy and therapeutic advances are urgently needed to improve response in these patients. In order to better treat these poor risk patients we aim, in this project, to develop a greater understanding of their disease, and from this identify specific cellular targets for future drug treatment/combination therapy.Read moreRead less
Chronic Myeloid Leukaemia: Changing The Treatment Paradigm
Funder
National Health and Medical Research Council
Funding Amount
$1,162,778.00
Summary
Most patients with chronic myeloid leukaemia achieve excellent responses to therapy but need therapy for life. We have pioneered the concept that some patients can cease their therapy and not relapse (treatment free remission –TFR). By studying the immune system and the leukaemic stem cells we will determine why TFR is possible for some, but not all patients. This holds the key to improving the rate of TFR, thus moving the CML goal from disease control to cure.
Assessment Of Markers Of Genomic Instability For The Prediction Of Treatment Response In Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$590,086.00
Summary
The success of therapy for patients with chronic myeloid leukaemia depends on close monitoring during therapy for early recognition of pending relapse, and the selection of appropriate treatment if drug resistance occurs. This project aims to identify patients at the start of therapy who are at risk of treatment failure by investigating their genetic profile. An increased frequency of gene mutations may indicate that patients require more aggressive therapy to achieve an optimal response.
Individualising Tyrosine Kinase Inhibitor Therapy In CML To Facilitate Successful Treatment Free Remission
Funder
National Health and Medical Research Council
Funding Amount
$376,449.00
Summary
This project will determine the optimal therapy for patients with chronic myeloid leukaemia (CML), matching the most appropriate drug to the individual patient, based on each patient's unique biology, thereby maximising the chance of cure. Furthermore, this project will develop novel highly sensitive tests for the presence of residual disease, even if undetectable by current techniques. This will enable crucial, timely treatment changes to be made with curative intent.
Translational Research Program To Advance Clinical Outcomes In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$418,192.00
Summary
Five-year survival in acute myeloid leukaemia (AML) is only 27%, placing it amongst the worst-ranked cancers for clinical outcome. Improved patient outcomes will be achieved through implementation of a Translational Research Program to support novel agent drug testing, early-phase and randomised clinical trials and a national clinical registry to audit outcomes. New insights into leukaemic stem cell function and mechanisms of drug resistance will inform the design of future clinical trials.
Roles Of The EMT Transcription Factors In Epigenetic Remodelling And Myeloid Cell Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$809,520.00
Summary
This project is based upon our novel discoveries that identified ZEB2 and SNAI1 as novel genes involved in the development of aggressive forms of blood cancer. During the course of this proposal we will find new drug targets and new drug treatment options using existing drugs that will specifically target cancer initiating cells in order to kill aggressive forms of blood cancers that are currently refractory to treatment.
Targeting The EGFR And C-Met Tyrosine Kinase Receptors In Myeloproliferative Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$607,559.00
Summary
We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can ....We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can be rapidly translated to clinical trial.Read moreRead less
GADD45A Promoter Methylation And Poor Prognosis In AML:mechanism And Clinical Significance
Funder
National Health and Medical Research Council
Funding Amount
$706,280.00
Summary
DNA methylation associated with the GADD45A gene defines an AML patient group with poor overall survival and limited treatment options. We will investigate the significance of this modification for the response of AML cells to chemotherapy and dissect the mechanism associated with this event. To translate these findings into the clinic we will test whether these patients are responsive to new agents targeting DNA methylation, and investigate survival of patients in a large independent cohort
Transposon Mutagenesis For Discovery Of Disease Causing Genes And Their Cooperative Interactions In Acute Myeloid Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$659,302.00
Summary
The emergence of cancer is caused by multiple mutations in normal cells. Recent progress has allowed the detection of virtually all mutations in a cancer genome. Although this has been enormous progress, it has become increasingly evident that only rare mutations are responsible for sustained tumour growth and treatment failure, while the majority of mutations are without effect. Our research will assist identification of the genetic changes essential to leukemia development, which will help dev ....The emergence of cancer is caused by multiple mutations in normal cells. Recent progress has allowed the detection of virtually all mutations in a cancer genome. Although this has been enormous progress, it has become increasingly evident that only rare mutations are responsible for sustained tumour growth and treatment failure, while the majority of mutations are without effect. Our research will assist identification of the genetic changes essential to leukemia development, which will help develop new cancer therapies.Read moreRead less