Targeting Sphingosine Kinase 1 To Sensitise Acute Myeloid Leukaemia To BH3 Mimetic Therapy
Funder
National Health and Medical Research Council
Funding Amount
$670,005.00
Summary
Acute Myeloid Leukaemia (AML) patients are currently treated with chemotherapeutics and despite their success at achieving disease remission these responses are often short lived, resulting in relapse and death. We have identified sphingosine kinase 1 as a new drug target in AML. This proposal aims to examine the role of targeting sphingosine kinase 1 in combination with new targeted therapies in patient samples and preclinical mouse models of AML.
Preclinical Evaluation Of A Novel Allosteric IL-1R Inhibitor (rytvela) For The Prevention Of Perinatal Inflammation-induced Fetal Injury
Funder
National Health and Medical Research Council
Funding Amount
$1,377,827.00
Summary
Interleukin-1 (IL-1) is a potent inflammatory protein involved in many inflammatory disorders, including preterm birth (PTB). Blocking the actions of IL-1 in pregnancies at risk of delivering preterm may protect the fetus from PTB and the long-term harm of exposure to inflammation before birth. Using four different models of antenatal inflammation, we will explore the use of a new IL-1 inhibitor to see if it blocks inflammation ‘in utero’ and improve neonatal health and development.
Preclinical Development Of TLR Signalling Inhibitors For Prevention Of Preterm Labour And Fetal Inflammatory Injury
Funder
National Health and Medical Research Council
Funding Amount
$690,821.00
Summary
Preterm birth affects 8% of Australian births and is a major cause of infant and child health problems. Therapies to prevent or delay prematurity are urgently required. This study will investigate new drugs that suppress the triggers of preterm labour. We will evaluate drug effects in mice and human placental tissue, to demonstrate safety and fetal protection from inflammatory injury that occurs with prematurity. Successful completion of the study is expected to lead to clinical trials in women.
Interaction Of TRP Channels And Inflammatory Mediators: A Critical Role In Visceral Pain
Funder
National Health and Medical Research Council
Funding Amount
$308,747.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we feel, such as touch and pain. The function of these channels can be altered by substances released by the body during inflammation. Some TRP channels have specialized roles in signalling pain from the colon which can be enhanced during colonic inflammation. Understanding how TRP channels and inflammatory mediators function and interact is essential if we are to find treatments for colonic pain.
Dissecting The Role Of The IL-3 Receptor Alpha Subunit And Beta-catenin In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$583,312.00
Summary
Leukaemia is a devastating form of blood cancer affecting both young and old. We aim to understand the mechanisms of uncontrolled cell growth associated with acute myeloid leukaemia. We focus on the role of key growth regulators that are abnormally active in the critical leukaemia stem cells. Understanding the biological and molecular properties of these cells is of considerable importance for development of the next generation of leukaemia therapies.
The Central Australian Heart Protection Study: A Randomised Trial Of Nurse-Led, Family Based Secondary Prevention Of Acute Coronary Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$1,923,630.00
Summary
Despite the high burden of cardiovascular diseases among Indigenous Australians, few intervention trials have sought to evaluate novel approaches to reducing differential outcomes in this vulnerable group. The Central Australian Heart Protection Study seeks to test the effectiveness of a nurse-led, family based education and assessment program in reducing the incidence of poor outcomes in indigenous and non-indigenous patient’s following an Acute Coronary Syndrome (ACS).
Many heart diseases are associated with impairment of energetics of the heart. Improving the heart's energetics can lead to improved survival and long-term outcomes. Perhexiline is a heart medication that works by improving the way the heart uses energy. Although effective, it is associated with long-term toxicities. Better understanding of this medication may lead to less adverse effects and also provide a basis for further investigation of drug development in the future.
Airway Epithelial IAPs And Their Interaction With Zn Ions
Funder
National Health and Medical Research Council
Funding Amount
$260,779.00
Summary
The air we breathe contains a variety of harmful substances. Damage to the lining involves death of the ciliated cells that line the airways. We have shown that zinc protects these cells from premature death. This application focuses on a family of proteins called IAPs which bind zinc and regulate cell death in other tissues. This project focusses on how the IAPs and Zn may act together to mainitain healthy airways and how abnormalities of these may occur in people with asthma.
Chronic inflammation underlies common and debilitating diseases and causes pain by unknown mechanisms. There is an urgent need to gain a deeper understanding of the mechanisms of chronic pain, which will allow the development of improved therapies with fewer side-effects. Our research program investigates the mechanisms of pain that are associated with inflammatory bowel disease and irritable bowel syndrome, with the goal of developing more effective and selective therapies.