Role Of MACROD2 Loss In DNA Repair, Chromosomal Instability And Development Of Colorectal Cancer: Clinical And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$772,871.00
Summary
The MACROD2 gene is deleted in one-third of human bowel cancers. We have discovered that MACROD2 deletion causes defective DNA repair and tumour chromosomal instability. Here, we will use novel laboratory models to show that MACROD2 loss actively promotes bowel cancer development. We will test the clinical implication of MACROD2 loss for predicting tumour therapy response and will investigate the potential of exploiting this deficiency for drug targeting.
Adoptive Cell Transfer Incorporating Vaccination (ACTIV) Therapy For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$601,950.00
Summary
We have made a breakthrough in a new treatment for cancer that can destroy large tumours in mice. The treatment involves a transfusion of white blood cells and an injection of a vaccine. In this project, we will seek to understand how the treatment works, and apply it to human white blood cells in preparation for a clinical trial in cancer patients.
Adenosine Receptor Antagonists As Immunotherapeutic Agents For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$555,779.00
Summary
We have shown that drugs that block immunosuppressive adenosine receptors can improve anti-tumour immune responses and consequently enhance the effectiveness of chemotherapy. These drugs are already known to be well-tolerated in humans and so have great potential for clinical development. We propose to determine the therapeutic response achieved with these drugs in combination with established cancer treatments involving radiotherapy and immune based therapies.
Transcriptional Effectors Of Oncogenic ERK Signaling In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$820,776.00
Summary
This project aims to unravel how one of the most frequently deregulated molecular pathways in colorectal cancer controls the expression of genes required for these tumours to grow and spread. We expect this work to uncover novel therapeutic targets to effectively inactivate this pathway and biomarkers to select patients most likely to benefit from existing therapies.
Elucidating The Cellular Processes That Are Critical For P53 Mediated Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$1,016,108.00
Summary
p53 is a tumour suppressor gene that is mutated in ~50% of human cancers. Mutations in p53 cause development of cancer and render malignant cells resistant to chemotherapy. We have identified genes regulated by p53 that appear critical for its tumour suppressive function. In this project, we will use innovative novel genetic tools to discover the cellular and biochemical functions of these genes. The ultimate goal of our studies is to identify novel targets for anti-cancer therapy.
Investigating The Anti-tumour Efficacy And On Target Toxicity Of Gene-modified T Cell Therapy In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$337,614.00
Summary
White blood cells from cancer patients can be modified in the laboratory to react against tumours. Although these cells can induce cancer regression when given back to the patient, these cells can often cause associated pathology. In this study we propose to fully investigate the limits of this type of therapy for mediating anti-tumour responses and potential toxicity in mouse models that closely recapitulate the human setting. These studies will lead to a more effective therapy for patients.
Defining The Role Of Reserve Stem Cells In Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$563,739.00
Summary
Over 800,000 deaths from stomach cancer occur annually. This often fatal disease is caused by chronic inflammation of the stomach lining. This proposal will investigate how stomach inflammation ‘reprograms’ a new type of 'cancer stem cell' to form tumours and evaluate ways to therapeutically target these cells to prevent disease. Collectively, these studies will inform new approaches for stomach cancer prevention and treatment.
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.
Identifying The Pathological Mechanism Of PCDH19-Girls Clustering Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$523,988.00
Summary
Changes in the PCDH19 gene are a relatively common cause of epilepsy. To better understand the basis of this disorder, we have developed unique mouse models that mimic the genetic changes and symptoms of this condition. We will perform careful analysis of brain development in these models to determine the primary cause of this condition. These experiments will create greater understanding of how changes in PCDH19 cause epilepsy in girls and facilitate the development of new treatments.
New Drug Combinations To Enhance Elimination Of Hepatitis B Infection
Funder
National Health and Medical Research Council
Funding Amount
$888,304.00
Summary
We have developed a therapy that kills hepatitis B virus infected cells and promotes elimination of infection. We are now testing novel drugs that can be used to maximise the efficacy of our new treatment to promote better outcomes that may be translated to other infections.