Targeting Lipid Signalling Receptors To Promote Remyelination In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$925,907.00
Summary
Multiple sclerosis is caused by the immune system mistakenly attacking and depleting myelin, the fatty substance that insulates neurons in our nervous system. To improve MS therapy and open up the possibility for functional recovery, we must develop drugs that protect and regenerate myelin. We will define how the loss of certain key biochemical signals promotes myelin loss in MS, and how drugs that restore those signals may be used to protect and regenerate myelin in people with the disease.
Defining The Role Of A Palmitoylated Variant Of Sphingosine Kinase 1 In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$603,452.00
Summary
Sphingosine kinase is a protein that when dysregulated is involved in cancer development and progression. We have recently made a substantial breakthrough in this area by identifing a naturally occuring variant of sphingosine kinase that is constantly activated and has an enhanced ability to induce cancer. In this study we will examine and target this form of sphingosine kinase as a potential therapeutic intervention in cancer.
Myelin Lipid Breakdown Affected By Apolipoprotein E Genotype: Implications For Alzheimer’s Disease Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$534,644.00
Summary
This project pieces together two important questions about Alzheimer’s Disease: (1) Why a naturally occurring variant of a gene called “APOE“ is the primary genetic risk for Alzheimer’s. (2) Why Alzheimer’s preferentially affects brain regions that lose a fatty substance called myelin, the electrical insulation of the brain. In doing so, we will understand more about what makes people more susceptible to Alzheimer’s and whether therapies to restore myelin could be effective against Alzheimer’s.
Altered Myelin Sphingolipid Homeostasis In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$629,532.00
Summary
Alzheimer’s Disease (AD) is the most common form of dementia, and its incidence is rising as the population ages. This project will provide a detailed analysis and explanation for the loss of particular lipid (fat) molecules that are essential for myelin integrity, in the brains of AD patients. Myelin is the insulating layer that surrounds brain cells, facilitating the transmission of electrical signals. This research will improve our understanding of how brain functions are impaired in AD.
Identification And Therapeutic Modulation Of Sphingolipids As Novel Lung Macrophage-targeted Treatments For COPD/emphysema
Funder
National Health and Medical Research Council
Funding Amount
$694,704.00
Summary
COPD/emphysema is predicted to be the third leading cause of death woldwide by 2010. We have shown defective lung macrophage function in COPD and have shown that we can modify the macrophage function with novel therapies. We are now investigating a specific “sphingosine” pathway to see if it can provide us with more specific information. We aim to provide a better, more specific, adjunct treatment for the disease.
Roles And Regulation Of Sphingosine Kinase 1 During Dengue Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$482,795.00
Summary
Dengue virus (DENV) infection is a global human disease with an estimated 50 million infections annually and there is no vaccine or therapy. DENV disease is worsended by the way the body responds to infection and we have investigated these responses. We know the virus changes a molecule in the body called sphingosine-kinase 1 (SK1), which normally controls if cell live or die and how they function. This study will characterise how DENV influences SK1 and if we can target this interaction to deve ....Dengue virus (DENV) infection is a global human disease with an estimated 50 million infections annually and there is no vaccine or therapy. DENV disease is worsended by the way the body responds to infection and we have investigated these responses. We know the virus changes a molecule in the body called sphingosine-kinase 1 (SK1), which normally controls if cell live or die and how they function. This study will characterise how DENV influences SK1 and if we can target this interaction to develop new drugs against DENV infection.Read moreRead less
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.
Modulating Sphingolipid Signalling To Enhance Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$698,447.00
Summary
Impaired wound healing is a major problem for diabetics, who often suffer with chronic unresolved wounds with serious effects on their quality of life and mortality. We have recently discovered a new pathway involving sphingolipids that shows great promise to improve wound healing in diabetics. In this project we will examine the targeting of this pathway, using existing and newly developed agents, to improve wound healing in advanced pre-clinical models of diabetes.
The steroid hormone estrogen plays a critical role in the development of human breast cancer. Anti-estrogen therapy has been believed to be an effective treatment of breast cancer over more than 100 years. However, the anti-estrogen therapy is still restricted mainly because of that estrogen has fundamental physiological actions and a wide range of beneficial effects on bone, brain, cardiovascular and other targeted tissues. Thus, it has become a primary focus of inquiry to understand how estrog ....The steroid hormone estrogen plays a critical role in the development of human breast cancer. Anti-estrogen therapy has been believed to be an effective treatment of breast cancer over more than 100 years. However, the anti-estrogen therapy is still restricted mainly because of that estrogen has fundamental physiological actions and a wide range of beneficial effects on bone, brain, cardiovascular and other targeted tissues. Thus, it has become a primary focus of inquiry to understand how estrogen specifically functions in breast cancer but not in normal tissues. Estrogen serves different functions involving a series of biochemical reactions called signal transduction pathways that can couple estrogen to a specific function, such as cancer formation. We have recently found that a enzyme named sphingosine kinase (SK) activation triggers a novel signal transduction pathway in regulation of cell growth and tumour formation, and that this pathway was activated by estrogen in human breast cancer cells. Thus, we seek to identify how estrogen activate SK and how they contribute to the development of breast cancer. It will ultimately provide a potential target for therapeutic intervention and may yield new compounds that have clinical benefit for anti-breast-cancer.Read moreRead less