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.
Is The Tumour Suppressor Activity Of P53 Independent Of Its Transcriptional Role?
Funder
National Health and Medical Research Council
Funding Amount
$162,920.00
Summary
To become cancerous, a cell must avoid death. As such, cancer cells often contain defects in cell death pathways which render them resistant to pro-death stimuli, including many chemotherapeutic drugs. To design new and better cancer therapies, it is essential that we understand the critical molecular processes that control cell death. This will allow the development of more effective ways to either reset, or bypass, defects in cell death pathways which have contributed to cancer formation.
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.
Mechanisms Of Cytokine Independence During The Development Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
Signals from growth factors such as cytokines and hormones are required for cell survival. In their absence cells activate an in-built self-destruct process. Determining how cytokines regulate cell death will provide novel targets so that unwanted cells (like cancer cells) can be triggered to die and needed cells (such as brain cells) can survive.
I am a cancer researcher trained in cell biology, immunology and molecular oncology. I made major contributions to the discoveries that defects in cell death can cause cancer, autoimmune disease and impair the response of cancers to chemotherapy. My current work aims to reach a detailed understanding of the molecular mechanisms of programmed cell death and to exploit this knowledge to develop novel therapeutics for cancer and autoimmune diseases that can directly activate this process.
Role Of Insulin-like Growth Factor Binding Protein-3 As A Mediator Of Apoptosis In Human Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$352,234.00
Summary
Human breast cancer, like other human cancers, is characterised by a disruption of normal cellular growth due to defects in the control of both cell proliferation and cell death. Understanding how these processes are regulated in normal and cancerous breast cells is an important goal for breast cancer treatment. Insulin-like growth factor binding protein (IGFBP)-3 is a regulator of normal and cancerous breast cell growth and has been implicated as a negative prognostic indicator for breast cance ....Human breast cancer, like other human cancers, is characterised by a disruption of normal cellular growth due to defects in the control of both cell proliferation and cell death. Understanding how these processes are regulated in normal and cancerous breast cells is an important goal for breast cancer treatment. Insulin-like growth factor binding protein (IGFBP)-3 is a regulator of normal and cancerous breast cell growth and has been implicated as a negative prognostic indicator for breast cancer progression. IGFBP-3 inhibits the growth of breast cancer cells and causes them to die by a process called apoptosis. We are determining how IGFBP-3 causes breast cancer cells to die by apoptosis. In particular, we are investigating whether IGFBP-3 may make breast cancer cells more sensitive to the apoptotic effects of ionising radiation and chemotherapeutic drugs which are both current therapies for the treatment of breast carcinoma. These studies may, in turn, elucidate the mechanisms that lead to increased resistance of breast cancers to these treatments.Read moreRead less
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