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Determinants Of Tissue- And Ligand-Specific Responses At The Mineralocorticoid Receptor
Funder
National Health and Medical Research Council
Funding Amount
$668,485.00
Summary
The steroid hormone aldosterone controls salt balance and hence, blood pressure. It also has been shown to have a significant role in cardiac failure. Although drugs that block the aldosterone receptor are beneficial in the treatment of heart failure, they are limited by potassium retention in the kidney. In order to develop tissue-specific blockers of the aldosterone receptor, it is necessary to identify mechanisms by which the receptor can be activated and/or blocked in specific tissues.
Cardiovascular disease is a leading cause of death in Australia, accounting for 36% of all deaths in 2004-05. Diseased blood vessels are its most common form, and the underlying process is atherosclerosis. Atherosclerosis is characterised by plaque formation in blood vessels. Plaque formation is problematic, and may lead to blood vessel blockage. We aim to identify novel targets that prevent plaque formation.
Mineralocortioid Receptor-Mediated Injury In Progressive Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$707,008.00
Summary
Diabetes is the major cause of kidney failure. Activation of a hormone receptor (the mineralocorticoid receptor-MR) can promote kidney injury. Current drugs blocking MR can suppress diabetic kidney disease but are limited by their poor specificity and harmful side effects. Our study will help improve strategies for blocking MR by identifying the cell types responsible for MR-mediated injury and by examining whether a new class of drug targeting MR is a superior therapy to current MR inhibitors.
The steroid hormone aldosterone controls salt balance and hence, blood pressure. It also has been shown to have a significant role in cardiac failure. Although drugs that block the aldosterone receptor are beneficial in the treatment of heart failure, they are limited by potassium retention in the kidney. In order to develop tissue-specific blockers of the aldosterone receptor, it is necessary to identify mechanisms by which the receptor can be activated and/or blocked in these tissues.
Development Of Selective Melanocortin Receptor Agonists And Antagonists
Funder
National Health and Medical Research Council
Funding Amount
$684,607.00
Summary
Human melanocortin receptors play a key role in a variety of physiological processes ranging from energy regulation, skin pigmentation and regulation of food intake. This project aims to generate novel peptide based molecules that will selectively interact with different melanocortin receptors to better understand their pharmacology thereby opening the potential for future drug development for obesity, stroke or inflammatory skin disorders.
Development And Application Of A Novel Ultrasensitive LC-MS Estradiol Assay
Funder
National Health and Medical Research Council
Funding Amount
$240,400.00
Summary
This project will develop a new ultrasensitive method using liquid chromatography-mass spectrometry to measure extremely low level of circulating estrogens in the bloodstream especially in mice. This will allow for the first time the ability to study the natural regulation of fertility in mice and other sub-primate mammals for which the present assay methods are not adequate.
Elf5 And The Basis For Antiestrogen Resistant Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,181,326.00
Summary
Resistance to anti estrogen therapies causes half of breast cancer deaths. We have recently discovered (Plos Biol 2012) that the transcription factor Elf5 is intimately involved in this process. This grant will develop our understanding of the transcriptional and genomic events involving Elf5 that lead to antiestrogen resistance and metatstasis, to develop new models of antiestrogen resistance, biomarkers that predict antiestrogen resistance and new therapeutic targets and strategies that preven ....Resistance to anti estrogen therapies causes half of breast cancer deaths. We have recently discovered (Plos Biol 2012) that the transcription factor Elf5 is intimately involved in this process. This grant will develop our understanding of the transcriptional and genomic events involving Elf5 that lead to antiestrogen resistance and metatstasis, to develop new models of antiestrogen resistance, biomarkers that predict antiestrogen resistance and new therapeutic targets and strategies that prevent antiestrogen resistance.Read moreRead less
Do Sex Hormones Slow Biological Ageing To Improve Health Outcomes In Men?
Funder
National Health and Medical Research Council
Funding Amount
$249,569.00
Summary
As the Australian population ages their burden of ill-health increases. Our earlier research showed that higher sex hormone levels are associated with better health outcomes in older men. In this project, we will address the question whether exposure to higher sex hormone levels slows biological ageing in men, reflected in the presence of longer chromosomal ends called telomeres. If so, interventions that raise hormone levels could be tested to preserve health in ageing men.
Adjunctive Hormone Therapy For Treatment Resistant Depression In Perimenopausal Women
Funder
National Health and Medical Research Council
Funding Amount
$620,946.00
Summary
Women entering the menopause have increased rates of treatment resistant depression with poor response to standard antidepressant treatment. We propose to conduct a clinical trial of a novel adjunctive hormone, tibolone, to improve the outcomes for middle – aged women with severe depression.
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.