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.
Identification Of A Genetic Defect Characterized By Radiosensitivity And Defective P53 Stabilization
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
Radiation is an important therapeutic agent for the treatment of a variety of cancers. However, radiation also causes cancers, certainly at high doses but it remains unclear as to the threat from low dose radiation eg in the vicinity of radiation accidents and at high altitudes. A greater understanding of the threats of radiation exposure is possible from the study of a number of rare syndromes characterized by extreme sensitivity to radiation and predisposition to develop cancer. The identifica ....Radiation is an important therapeutic agent for the treatment of a variety of cancers. However, radiation also causes cancers, certainly at high doses but it remains unclear as to the threat from low dose radiation eg in the vicinity of radiation accidents and at high altitudes. A greater understanding of the threats of radiation exposure is possible from the study of a number of rare syndromes characterized by extreme sensitivity to radiation and predisposition to develop cancer. The identification of new syndromes with radiosensitivity assists in delineating the overall response to radiation and the connection with cancer. This project is designed to identify the molecular basis of what appears to be a novel defect. It has some of the characteristics of a well described syndrome ataxia-telangiectasia (A-T), namely signs of neurodegeneration and sensitivity to radiation but the protein defective in A-T appears to have normal function in this case. A comprehensive investigation of a number of pathways of radiation signaling is planned to identify the nature of the defect.Read moreRead less
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
Macrophage Migration Inhibitory Factor (MIF) And P53 In Rheumatoid Arthritis .
Funder
National Health and Medical Research Council
Funding Amount
$333,055.00
Summary
Rheumatoid arthritis (RA) is an inflammatory disease affecting approximately 1% of the population. It is characterised by severe inflammation and destruction of joints resulting in significant health problems. The lining tissue of joints is known to be infiltrated by inflammatory cells. In addition to this infiltration of inflammatory cells, there is overgrowth of the normal lining cells of joints. These overgrowing cells contribute significantly to joint damage by invading cartilage and bone an ....Rheumatoid arthritis (RA) is an inflammatory disease affecting approximately 1% of the population. It is characterised by severe inflammation and destruction of joints resulting in significant health problems. The lining tissue of joints is known to be infiltrated by inflammatory cells. In addition to this infiltration of inflammatory cells, there is overgrowth of the normal lining cells of joints. These overgrowing cells contribute significantly to joint damage by invading cartilage and bone and allowing inflammatory cells to reach these areas. The abnormal growth of these cells has been related to the malfunction of certain genes that usually restrain abnormal growth. These genes called tumour suppressor genes are known to be damaged in joint lining cells derived from RA. The best known of these abnormal tumour suppressor genes is called p 53. The product of the p53 gene, the p 53 protein, is particularly important in slowing down the growth of cells. The applicant has recently shown that an inflammatory product called MIF is released in large quantities by joint lining cells in RA. Previous studies by the applicant have shown that blocking MIF using an antibody almost completely prevents arthritis development in a rat model. These studies indicate that MIF is likely to be an important contributor to disease in RA. Recent preliminary studies in the applicant s laboratory have shown that MIF can decrease p53 levels in joint lining cells from RA patients and also that MIF can increase the growth rate of these cells. These preliminary data indicate that MIF may contribute significantly to disease in RA by overriding control of normal cell growth by p53. Confirmation and full exploration of the regulation of p53 expression and function by MIF may highlight a novel way to treat the excessive growth and invasion by joint lining cells which characterises RA.Read moreRead less
Targeting MYC-driven Cancers By Inhibition Of The MTOR Pathway
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
This proposal will evaluate a new strategy for treating cancers associated with the cancer causing gene MYC. Globally there are more than 1 million cases of MYC-associated cancers diagnosed per year. Based on encouraging early results we will test if turning off the proteins associated with mTOR will be an effective strategy for treating MYC cancers using state-of-the-art cancer models and investigate why these cancers respond.