I am interested in determining the molecular basis of immune recognition of foreign and self-antigens in the context of viral, tumor and auto-immunity as well as transplantation. In addition to fundamental observations this knowledge is also applied in va
Improving Outcomes For Cancer Patients By Targeting The Epigenome
Funder
National Health and Medical Research Council
Funding Amount
$2,258,892.00
Summary
The most commonly mutated proteins in cancer involve so called epigenetic regulators, a class of proteins that regulate access to our DNA to control gene expression, DNA repair and replication. We and others have recently developed a variety of drugs to help inhibit the aberrant activity of these epigenetic proteins. My research will focus on ways to improve the efficacy of these existing drugs and find new epigenetic therapies to improve the survival of patients with a broad range of cancers.
Plasminogen activator inhibitor type 2 (PAI-2) or SerpinB2 is a protein that has been extensively studied in the field of cancer prognosis and inflammation. Although it is widely believed that this protein exists outside the cell and inhibits enzymes involved in blood clotting and cell migration, it is becoming increasingly clear that this may not be its primary function. We have identified two important new functions for this protein that are related to activities within the cell. These activit ....Plasminogen activator inhibitor type 2 (PAI-2) or SerpinB2 is a protein that has been extensively studied in the field of cancer prognosis and inflammation. Although it is widely believed that this protein exists outside the cell and inhibits enzymes involved in blood clotting and cell migration, it is becoming increasingly clear that this may not be its primary function. We have identified two important new functions for this protein that are related to activities within the cell. These activities involve regulation of cellular growth and resistence to viral infections. This grant seeks to characterise these different activities and determine how they affect cell behaviour and thereby determine the real role of this protein. Understanding what this protein actually does will have implications for understanding cancer prognosis and antiviral resistance.Read moreRead less
Remodelling Of Bacterial Outer Membranes: Implications For Vaccine Development.
Funder
National Health and Medical Research Council
Funding Amount
$558,189.00
Summary
We have identified proteins located in bacteria that are responsible for growth and the transport of essential nutrients. We will use a combination of bacterial genetics, protein biochemistry and immunological techniques to fully characterize these proteins. This strategic knowledge has direct implications for vaccine development and National security, since similar species of bacteria were amongst the first biological weapons.
Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people w ....Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people with prothrombotic pathologies.Read moreRead less
Role Of Sirtuins In The Regulation Of The Carcinogen Metabolising Arylamine N-acetyltransferases
Funder
National Health and Medical Research Council
Funding Amount
$327,324.00
Summary
This project will investigate critical biochemical pathways that regulate metabolic differences in normal and cancer cells. By understanding how these processes differ, novel approaches for detecting and managing cancer cell proliferation in humans may be achievable.
GPI Anchored Forms Of The Dengue Virus NS1 Protein: Production And Role In Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$203,448.00
Summary
Dengue viruses are carried by mosquitoes and infect millions of people around the world, particularly in tropical countries of SE Asia, Central and South America, Africa and recently in Australia (North Queensland and NT). There is no vaccine or drug available for preventing or treating the infections, which are characterised by severe illness that involves inflammation and fevers that can sometimes be fatal. This study focuses on an unusual form of a dengue virus protein (called NS1) which we h ....Dengue viruses are carried by mosquitoes and infect millions of people around the world, particularly in tropical countries of SE Asia, Central and South America, Africa and recently in Australia (North Queensland and NT). There is no vaccine or drug available for preventing or treating the infections, which are characterised by severe illness that involves inflammation and fevers that can sometimes be fatal. This study focuses on an unusual form of a dengue virus protein (called NS1) which we have identified. We plan to study the role that this protein plays in the more severe and often fatal forms of dengue infection (dengue haemorrhagic fever and dengue shock syndrome). In these more severe and life threatening forms of dengue the blood vessels of these patients become leaky. It is thought that this is caused by the secretion of certain chemicals (cytokines) from infected cells. We have shown that dengue infected human cells, which have the unusual form of NS1 protein on their surface, are capable of being activated by antibodies. Antibodies are proteins which are produced by the human body to fight infection. We aim to study whether cytokines are secreted from infected human blood cells activated in this way and whether these cytokines cause blood vessels to become leaky. We will also study how the virus produces this variant form of NS1 in the two host species that the virus infects; mosquito and human. These studies will increase our understanding of dengue virus infection and will provide valuable information concerning the role that this unusual form of the degue virus protein NS1 plays in the severe forms of dengue fever; dengue haemorrhagic fever and dengue shock syndrome.Read moreRead less
A Temporal Profile Of Signaling Via Phosphorylation During Myocardial Ischemia - Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$369,641.00
Summary
Cardiovascular disease (CVD) is the major cause of death in Australians and sequelae post-myocardial ischemia - reperfusion (I-R) are responsible for the greatest proportion of CVD-related mortality. Despite this burden, there is little known of the molecular events that mediate I-R. This project will utilize cutting-edge technology to elucidate the molecular signaling events that lead to I-R injury, as well as determine the basis for protection afforded by clinical pre- and post-conditioning.