Investigating The Role Of Mutant P53 And MCL-1 In The Sustained Growth Of MYC Lymphomas And Strategies For Targeted Therapy
Funder
National Health and Medical Research Council
Funding Amount
$616,940.00
Summary
A large number of human cancers have abnormal expression of a protein called MYC, leading to rapid growth. We found that when another protein called MCL-1 was inactivated, the lymphomas regressed. Importantly, mutations in the tumour suppressor gene called p53 are frequently found in cancer cells and we noticed that this could reduce the dependency on MCL-1. We aim to investigate this further in this grant proposal, in part using a novel drug that targets MCL-1.
Learning The Mechanisms Of Programmed Cell Death And Tumour Suppression To Develop Novel Cancer Therapies
Funder
National Health and Medical Research Council
Funding Amount
$863,910.00
Summary
Our bodies prevent the development of cancer through tumour suppressive processes, which also affect the outcome of cancer therapy. Programmed cell death (apoptosis) is one such process, and defects in apoptosis promote cancer development and impair the response of tumour cells to anti-cancer therapies. My laboratory uses molecular biology and cell biology approaches to investigate the mechanisms of cell death and tumour suppression, partnering with pharma to develop novel cancer therapies.
Examining The Contribution Of Mutant DNMT3a In The Development And Sustained Growth Of Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$820,880.00
Summary
Experimental models of Acute Myeloid Leukaemia (AML) have been valuable tools for studying this cancer. Recent analysis of human cancer genomes identified novel mutated gene products implicated in AML. To study the involvement of these genes in the development and sustained growth of AML, we will generate new experimental models that express the mutated forms of these newly described genes. These studies will assist in the development of improved treatments for patients with AML.
DOES BCL-G, A BH3-ONLY PROTEIN, PLAY A ROLE IN INFLAMMATION-ASSOCIATED COLON CANCER?
Funder
National Health and Medical Research Council
Funding Amount
$418,587.00
Summary
Deregulation of the function of several members of the Bcl-2 family has been shown to be an aggravating factor in autoimmune diseases and cancer. Bcl-G is a new and poorly characterized member of this family. We have produced essential tools to study the physiological function of Bcl-G, and discovered that it plays a role in inflammatory bowel disease. We now plan to investigate its possible role in inflammation-associated colon cancer.?
Dual Targeting Of Myc And Apoptosis Pathways For Improved Blood Cancer Treatment Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$754,685.00
Summary
Cancer cells frequently possess defects in genes called MYC and BCL-2 that control their growth and survival. Our preliminary studies have shown that combining novel reagents that specifically target MYC plus BCL-2 leads to enhanced lymphoma cell killing. In the proposed research, we will further develop these reagents and evaluate their ability to treat blood cancer in mice. We expect our approach will provide new avenues for treating cancer patients that respond poorly to current treatments.
Understanding How BH3-only Proteins Initiate Apoptosis In Response To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$481,124.00
Summary
Failure to initiate cell death is a hallmark in the development of the majority of cancers and killing all tumour cells is essential for effective cancer treatment. A group of proteins termed the BH3-only proteins normally sense cell stress to trigger cell death. Their dysregulation contributes to cancer and failure to respond to chemotherapy. Understanding how these proteins function to induce cell death will allow the design of drugs that mimic this activity for improved cancer therapy.
Glucose Toxicity-induced Activation Of The Bcl-2-regulated Apoptotic Pathway In Pancreatic Beta Cells
Funder
National Health and Medical Research Council
Funding Amount
$617,238.00
Summary
High blood glucose or hyperglycaemia is a feature of type 2 diabetes. Hyperglycaemia and fatty acids in the blood can cause damage of the insulin-producing pancreatic beta cells, resulting in worsening of diabetes. We plan to elucidate the pathways in beta cells that are stimulated by high levels of glucose and fatty acids, and to determine if these pathways are turned on in the pancreas of patients with type 2 diabetes, to try and identify targets for new therapies.
Developing Novel Anti-cancer Agens By High Throughput Chemical Screens For Small Molcules That Modulate The Pro-survival
Funder
National Health and Medical Research Council
Funding Amount
$125,000.00
Summary
Cancer is the second commonest cause of deaths in our community. Unfortunately, treatment often fails or causes unwanted side effects. This proposal seeks to discover and develop a novel class of anti-cancer drugs that act by directly activating programmed cell death (apoptosis). The Bcl-2 proteins are key regulators of cell death and by exploiting knowledge about these prime targets for cancer therapy, we aim to discover drugs that are potentially of considerable medical and commercial value.
Defining The Requirement For The Inhibition Of Bak To The Pathogenesis Of Cytomegalovirus Infection
Funder
National Health and Medical Research Council
Funding Amount
$592,661.00
Summary
Apoptosis, or programmed cell death is a powerful defence mechanism against viral infection. Thus, to replicate efficiently viruses have evolved means to inhibit apoptosis. The central aim of this work is to understand how cytomegalovirus prevents cell death protein during infection. The proposed studies will improve our understanding of the mechanisms that regulate viral replication and will contribute insights into the normal processes that control cell survival.