Hormone Transport By Alpha-2-Macroglobulin: Novel Roles In Regulating Hormone Activity
Funder
National Health and Medical Research Council
Funding Amount
$602,857.00
Summary
Alpha-2-macroglobulin is a large protein in the blood known to bind and transport numerous hormones in the circulation. Our previous studies published in BLOOD (2009) and JBC (2013) have discovered an important role for this molecule in the transport and regulation of a peptide hormone. The studies proposed in this application have important implications for understanding new roles of alpha-2-macroglobulin in hormone binding and regulating the activity of hormones in disease states.
Dual Targeting Of The Androgen Receptor For Effective And Durable Control Of Lethal Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$946,177.00
Summary
Preventing binding of androgens to the androgen receptor is the mainstay treatment for advanced prostate cancer, but resistance inevitably develops and the disease becomes lethal. We will develop a new drug that targets a part of the androgen receptor unrelated to its androgen binding function to overcome resistance to current therapy. As this drug will be effective in all stages of prostate cancer, it has high potential to improve survival outcomes for men with prostate cancer.
Characterising The Novel Signalling Mechanism For A New Interferon
Funder
National Health and Medical Research Council
Funding Amount
$525,485.00
Summary
We have discovered a new regulatory protein called interferon epsilon, made in the female reproductive tract and is crucial for protection against bacterial( Chlamydia) and viral (Herpes Simplex Virus) infections. However, we are yet to understand how it interacts with target cells. This grant will study how IFN? binds to cells and the nature of the signals it transmits. This will help us understand its role in disease and its clinical potential
Does Teriparatide Reverse Osteonecrosis Of The Jaw In Patients With Cancer? A Randomised, Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$357,412.00
Summary
Osteonecrosis of the jaw (ONJ) is debilitating and associated with drugs that increase bone strength and reduce the bone remodeling rate (bisphosphonates or denosumab). Up to 15% of patients with bone marrow cancer and 1 out of 952 patients with osteoporosis treated with bisphosphonates may get ONJ. This 8-week trial of subcutaneous teriparatide (a hormone that forms new bone) or placebo injections aims to promote resolution of ONJ, measured clinically and by x-ray, and improve quality of life.
The Clinical Significance Of Sex Hormone Crosstalk In Estrogen Receptor Positive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$1,009,006.00
Summary
Breast cancer is mainly a disease in which the sex hormone estrogen stimulates uncontrolled growth. We have recently discovered that other sex hormones, including progesterone and androgen, can redirect the actions of estrogen in breast cancers to halt growth or make a tumour disappear. This study will examine the complex interaction between all three sex hormones to develop new, more effective strategies for treating breast cancer.
The Role Of Sorting Nexin 27 In Cargo-trafficking During Skeletal Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$623,327.00
Summary
Skeletal diseases encompass a devastating set of disorders ranging from heritable skeletal dysplasia’s such as dwarfism through to degenerate diseases like osteoporosis. This research project aims to determine the role of a protein called Sorting Nexin 27 (SNX27), normally involved in the transport of intracellular cargo (e.g. growth factor receptors), in the maintenance of the skeleton and its potential contribution to the pathogenesis of skeletal disorders.
Epigenetic Regulation Of Self Renewal And Lineage Commitment In Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$1,104,930.00
Summary
The process by which all our mature blood cells are produced and sustained remains largely unknown. Underpinning the cell fate decisions made through blood cell development is the tightly regulated expression of key genes and proteins that subsequently direct the process of blood cell differentiation. This project will aim study and uncover the molecular mechanisms that coordinate the key gene expression programs that lead to normal blood cell development.
Activation And Inhibition Of The Plasminogen/Plasmin System
Funder
National Health and Medical Research Council
Funding Amount
$800,663.00
Summary
Plasmin is crucial enzyme present in blood plasma that functions in clot dissolution, inflammation, tissue remodeling, and wound healing. We aim to study how this enzyme system is controlled, by studying its interaction with receptors, co-factors and inhibitors. The information we gain will help drive the development of new generation therapeutics for the fine control of plasmin function in clotting disease, bleeding and inflammation.
Discovery And Characterisation Of Novel Tick Evasins As Inhibitors Of Chemokine-mediated Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$654,847.00
Summary
An important aspect of inflammatory diseases is the migration of white blood cells into the affected tissues. This is controlled by a group of proteins called chemokines. Ticks, which live on mammalian hosts, produce proteins called evasins, which interact with host chemokines and thereby prevent inflammatory responses. This project will discover new tick evasins, study their chemokine interactions and investigate their ability to block inflammation in allergic asthma.