Interplay Between Mutant P53 And PML; Implications For Tumourigenesis.
Funder
National Health and Medical Research Council
Funding Amount
$483,737.00
Summary
The most important agent of the body for fighting cancer is the cellular protein p53. In more than 50% of all human cancers, it looses its anticancer properties through mutation. In an insidious manner this new mutant form then acts to promote cancer. To better treat cancer we need to understand how mutant p53 functions. We will study how it interacts with its molecular partners in cancer cells.
Restoration Of P53 Activity In Tumours: A New Approach Involving The P53 Coactivator ANKRD11.
Funder
National Health and Medical Research Council
Funding Amount
$465,990.00
Summary
p53 is an important protein that functions as the body�s defence mechanism against cancer. Mutation of p53 is observed in over half of all tumours. Not only do these cancer mutations abolish the ability of p53 to protect against cancer, but it also endows the tumours with an ability to spread throughout the body, or metastasize. In this research project, we will identify and develop targets that will not only prevent the spread of new tumours, but it will also re-activate the anti-cancer functio ....p53 is an important protein that functions as the body�s defence mechanism against cancer. Mutation of p53 is observed in over half of all tumours. Not only do these cancer mutations abolish the ability of p53 to protect against cancer, but it also endows the tumours with an ability to spread throughout the body, or metastasize. In this research project, we will identify and develop targets that will not only prevent the spread of new tumours, but it will also re-activate the anti-cancer function in mutant p53 leading to tumour regression.Read moreRead less
Cancer is constantly being suppressed in our bodies by a process that stops damaged cells from growing: 'senescence'. The mechanism that translates the damage stimuli into this state of permanent cell arrest is only partially known. We have identified a protein that appears to drive this restraint. The possibility of manipulating this process to prevent and cure cancer makes it in important target to study.
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.
DNA Repair Mechanisms In The Pathogenesis Of Hepatocellular Carcinoma
Funder
National Health and Medical Research Council
Funding Amount
$339,078.00
Summary
Hepatocellular carcinoma (HCC) or cancer originating in the liver ranks 5th in worldwide frequency among tumours, and is the 3rd highest cause of cancer in our region. The incidence is increasing in most countries including Australia, Japan and USA. The overall prognosis is poor, with >80% affected persons dying from this disorder. The risk factors for HCC are well known and include chronic hepatitis B or C virus infection, alcoholism and liver iron accumulation. Despite the vast amount of in ....Hepatocellular carcinoma (HCC) or cancer originating in the liver ranks 5th in worldwide frequency among tumours, and is the 3rd highest cause of cancer in our region. The incidence is increasing in most countries including Australia, Japan and USA. The overall prognosis is poor, with >80% affected persons dying from this disorder. The risk factors for HCC are well known and include chronic hepatitis B or C virus infection, alcoholism and liver iron accumulation. Despite the vast amount of information available regarding these risk factors, the way in which they alter normal liver cells to make them cancerous remains undefined. The majority of liver cancers, regardless of cause, develop in severely scarred, or cirrhotic liver in the presence of chronic liver inflammation. Such an environment causes liver cells, which are usually stable and not dividing, to continue replicating in response to injury; such continued cell division can lead to damaged genetic information in the DNA of these cells. Many cancers are associated with chromosomal damage, including broken ends and deleted genetic material. The main focus of this project to investigate how defective repair of disrupted genetic information contained in DNA of chromosomes in damaged liver cells contributes to the development of liver cancer. Using mice lacking specific genetic information to repair DNA double strand breaks, we plan to investigate whether abnormalities in DNA repair mechanisms in liver cells damaged by diethylnitrosamine (DEN) predisposes liver cells to regenerate abnormally thereby progressing to cancer. We have clues that 7 specific sites in chromosomes where loss of key genes may promote HCC formation. These studies will greatly enhance our understanding of the molecular basis by which HCC develops. The ultimate goal of this research is to develop effective screening and treatment strategies to prevent or interrupt the process of liver cancer development in at-risk individuals.Read moreRead less
We recently discovered a new way to treat melanoma by inhibiting a protein called MDM4 that is important in promoting tumor growth in ~2/3 of melanomas. In this proposal, we will extend this work to see if anti-MDM4 therapy is effective in laboratory models that are more relevant to patients and in combination with other melanoma therapies. We will also explore additional ways of inhibiting MDM4 that may make anti-MDM4 therapy even more potent.