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Prevention Of Pancreatic Beta Cell Destruction In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$621,458.00
Summary
Associate Professor Helen Thomas is a molecular and cell biologist with a particular interest in pancreatic islet biology, studying the mechanisms of pancreatic beta-cell destruction in diabetes. The aim of this work is to develop strategies to protect these cells. Such protection will improve our ability to preserve beta-cell mass in type 1 and type 2 diabetes, and after islet transplantation.
Mechanisms Responsible For Pancreatic Beta Cell Death And Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Diabetes is the fastest growing chronic disease both in Australia and worldwide. Current treatments are lacking effectiveness. Therefore, there is an urgent need to revolutionise diabetes therapy. Diabetes is caused by the failure of cells within the pancreas to produce sufficient insulin, resulting in uncontrolled blood sugar levels. This research proposal aims to investigate the processes and factors leading to this phenomenon in order to develop new strategies to overcome them.
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.
Mechanisms Of Mcl-1- And Bcl-2-mediated Resistance To Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$439,796.00
Summary
Anti-cancer therapies that target either the mitochondrial or death receptor pathways of apoptotic cell death are being developed and in clinical trials. In certain cancer cells, the tBid protein links the two pathways, making the death receptor pathway dependent on the mitochondrial pathway. Our studies will test how tBid links the two pathways and how the link might be bypassed, potentially indicating means of improving the effectiveness of treating cancer by targeting death receptors (e.g. TR ....Anti-cancer therapies that target either the mitochondrial or death receptor pathways of apoptotic cell death are being developed and in clinical trials. In certain cancer cells, the tBid protein links the two pathways, making the death receptor pathway dependent on the mitochondrial pathway. Our studies will test how tBid links the two pathways and how the link might be bypassed, potentially indicating means of improving the effectiveness of treating cancer by targeting death receptors (e.g. TRAIL).Read moreRead less
Manipulating Oncogenic-signalling Pathways In The Genesis And Treatment Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$601,484.00
Summary
Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life. The use of small molecule inhibitors is the most promising strategy for treating melanoma. In this project, we will examine the mechanisms of resistance to this class of drugs and define new drug targets by examining the molecular-circuitry is damaged in melanomas. This work will greatly accelerate the development of new therapi ....Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life. The use of small molecule inhibitors is the most promising strategy for treating melanoma. In this project, we will examine the mechanisms of resistance to this class of drugs and define new drug targets by examining the molecular-circuitry is damaged in melanomas. This work will greatly accelerate the development of new therapies.Read moreRead less
Manipulating The B-RAF/MEK Pathway In The Genesis And Treatment Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$562,815.00
Summary
Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life. The use of small molecule inhibitors is the most promising strategy for treating melanoma. In this project, we will examine the mechanisms of resistance to this class of drugs and define new drug targets by examining the molecular-circuitry that is damaged in melanomas. This work will greatly accelerate the development of new th ....Melanoma is a major Australian health problem. It is the third most common cancer in men and women and has a disproportionately heavy impact on productive years of life. The use of small molecule inhibitors is the most promising strategy for treating melanoma. In this project, we will examine the mechanisms of resistance to this class of drugs and define new drug targets by examining the molecular-circuitry that is damaged in melanomas. This work will greatly accelerate the development of new therapies.Read moreRead less
Controlling The Pro-survival Protein Mcl-1: Discovering Novel Opportunities And Developing Innovative Approaches To Target Mcl-1 For Treating Cancers
Funder
National Health and Medical Research Council
Funding Amount
$749,415.00
Summary
Cancer cells are often sustained by evading cell death. Thus, a promising approach to develop new cancer treatments aims to restore their ability to commit cell suicide. Proteins related to Bcl-2 are, in this regard, attractive targets because they are prominent barriers to cell death. This project seeks to uncover how a Bcl-2 relative, Mcl-1, is regulated, and to explore how the mechanisms that underpin these processes can be targeted in cancers (melanomas, leukemias) that it sustains.
The Bcl-2 Life/death Switch - Why Do Some Bcl-2 Proteins Kill Cells Whilst Others Promote Their Survival?
Funder
National Health and Medical Research Council
Funding Amount
$375,510.00
Summary
The cells of all animals possess the ability to commit suicide. When this natural process of cell death is dysfunctional, diseases such as cancer arise. Our aim is to understand the molecular mechanisms that underlie this process by providing atomic resolution snapshots of key components of the cell death machinery. By understanding the fine details of cell death regulation we can develop new drugs that target and kill rogue cells such as those found in tumours.
Regulation Of TNF Expression In Inflammation And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$728,447.00
Summary
By studying a spontaneous mutation in mice, we have found an error in the TNF gene (a major factor in many inflammatory diseases) that causes severe arthritis, heart valve disease and gut inflammation. We have also identified new regulators of TNF expression, which might be useful therapeutic targets to limit inflammation. We intend to study the role of these regulators in controlling the expression of TNF, and the link between chronic inflammation and the development of cancer.
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.