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.
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
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.
Function Of FOR Gene Products In Normal And Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$521,310.00
Summary
Cancer cells usually exhibit the loss of control of normal cell functions. This involves the increase of proteins which promote growth and cell division and the decrease in proteins which inhibit growth and cell division. Loss of function may also occur in proteins that are normally involved in killing the cell when growth becomes uncontrolled. Many of these proteins interact with one another and in so doing establish pathways and networks of control which must be perturbed and overridden in the ....Cancer cells usually exhibit the loss of control of normal cell functions. This involves the increase of proteins which promote growth and cell division and the decrease in proteins which inhibit growth and cell division. Loss of function may also occur in proteins that are normally involved in killing the cell when growth becomes uncontrolled. Many of these proteins interact with one another and in so doing establish pathways and networks of control which must be perturbed and overridden in the cancer cell. Sometimes this is because the role of the protein is altered in the cancer cell compared to what it normally is in a normal cell. The main aim of this study is to understand the role that is played by a set of proteins that are coded by a single gene. This gene (which we refer to as the FOR gene) spans a region of the human genome which is sensitive to a particular type of mutation. This mutation takes place early in tumour development and therefore we believe that it has important role to play in determining the fate of the cell - helping to cause it to become a tumour cell. We will find out which other proteins in the cell the FOR proteins interact with. Where these proteins are known then this will help determine the pathways in the cell in which the FOR proteins participate. In another approach we will establish animal models (in mice and flies) of mutations in the FOR genes of these species. The transgenic mice will help us find out whether the mutations that we have observed in the FOR gene in various human cancers cause increased sensitivity to mutagens and in so doing aid in transforming normal cells into cancer cells. The transgenic flies will help us identify the metabolic pathways in which the FOR proteins participate. These studies will help understand the roles of the FOR proteins and their significance in cancer.Read moreRead less
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.