Understanding Neuroinflammation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,043,216.00
Summary
This project opens a new line of enquiry into the cellular signalling mechanisms involved in the progression of AD and establishes whether targeting the involvement of type-1 IFN signalling influences the evolution of AD. New and novel approaches are clearly required to treat AD. Importantly, we believe that neuroinflammation is common to all causes of dementia and targeting the neuroinflammatory pathways has much wider implications than targeting the primary causative pathway.
Controlling Neuroinflammation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Summary
Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide, with 269,000 Australians currently diagnosed with AD and is expected to soar to about 981,000 by 2050. AD accounts for greater than 60% of all cases of dementia. This grant investigates the role that neuroinflammation plays in the progression and exacerbation of AD and will identify new therapeutic strategies to combat this insidious disease.
Testing The Prion Hypothesis In Parkinson’s Disease Using A Novel In Vivo Model Of Α-synuclein Transmission
Funder
National Health and Medical Research Council
Funding Amount
$622,555.00
Summary
Parkinson’s Disease (PD) is a debilitating neurological disease with no cure. Recently it has been discovered that the disease can spread through the brain. We have developed the worlds first animal model to study exactly how the disease propagates inside of neurons during this spread. We will use the model to answer key questions about this critical stage of disease spread, knowledge that is essential for the development of successful therapies to prevent disease progression.
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.
The Axis Of Bcl-2, Plasmacytoid DCs And Lupus As A Basis For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$712,172.00
Summary
Systemic lupus erythematosus (SLE) affects 1 in 1000 Australians, mostly women. Here the immune system goes awry and makes antibodies against the body’s own components including the body’s DNA. This leads to damage to many parts of the body including kidneys, joints, brain and heart. It is incurable. A particular immune cell controls the development of this disease and we have found this cell is selectively killed by an inexpensive drug, which we hope will be a better way of treating SLE.
Examining The Contribution Of Mutant DNMT3a In The Development And Sustained Growth Of Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$820,880.00
Summary
Experimental models of Acute Myeloid Leukaemia (AML) have been valuable tools for studying this cancer. Recent analysis of human cancer genomes identified novel mutated gene products implicated in AML. To study the involvement of these genes in the development and sustained growth of AML, we will generate new experimental models that express the mutated forms of these newly described genes. These studies will assist in the development of improved treatments for patients with AML.
Apoptosis And Stem/Progenitor Cells In The Development And Treatment Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$21,809,604.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks. The first is excessive cell survival. To combat this, we are developing drugs with commercial partners that directly activate the cell's death machinery. The second hallmark is inexorable proliferation, akin to that of stem cells, which can generate entire tissues, as we showed for the breast. ‘Rogue’ stem-like cells may initiate certain cancers. We hope to advance cancer therapy by identifying such cells and drugs that kill them.
Toward Effective Targeted Therapies For Acute Myeloid Leukaemia (AML)
Funder
National Health and Medical Research Council
Funding Amount
$551,345.00
Summary
Standard chemotherapy for acute myeloid leukaemia (AML) is highly toxic, and has not changed in over 40 years. We will conduct a world-first clinical trial incorporating ABT-199 (Venetoclax) to target BCL2 into the standard-of-care treatment for AML. A second initiative will explore the potential for small molecule inhibitors to simultaneously target both BCL2 and its related partner MCL1, to create a “chemotherapy-free” regimen for AML. These studies promise to herald a new era in AML therapy.
A Novel Lipid Sensitive Kinase And Its Role In Obesity-induced Inflammation And Insulin Resistance.
Funder
National Health and Medical Research Council
Funding Amount
$560,045.00
Summary
It is now apparent that obesity leads to chronic low grade inflammation which results in insulin resistance or pre-diabetes. The mechanisms that link obesity-induced inflammation to insulin resistance are not well understood, but involve lipid oversupply. We have preliminary data identifying that a protein, not known to previously play a role in metabolic diseases, is a critical mediator of lipid-induced inflammation. We will investigate the clinical potential of blocking this protein.
Developing Novel Anti-cancer Agens By High Throughput Chemical Screens For Small Molcules That Modulate The Pro-survival
Funder
National Health and Medical Research Council
Funding Amount
$125,000.00
Summary
Cancer is the second commonest cause of deaths in our community. Unfortunately, treatment often fails or causes unwanted side effects. This proposal seeks to discover and develop a novel class of anti-cancer drugs that act by directly activating programmed cell death (apoptosis). The Bcl-2 proteins are key regulators of cell death and by exploiting knowledge about these prime targets for cancer therapy, we aim to discover drugs that are potentially of considerable medical and commercial value.