Combating Escalating Harms Associated With Pharmaceutical Opioid Use
Funder
National Health and Medical Research Council
Funding Amount
$925,767.00
Summary
Increases in opioid use have been accompanied by increased opioid harms. But there is a lack of population-level evidence about drivers of long-term prescribed opioid use, dependence, overdose and other harms. Using linked data, we will fill these gaps using a cohort of all people in NSW prescribed opioids since 2002, linked to datasets containing information on health, social and health service utilisation, that will permit a comprehensive assessment of the risks of all prescribed opioids.
Cognitive Enhancement In Schizophrenia Via Selective Oestrogen Receptor Modulator.
Funder
National Health and Medical Research Council
Funding Amount
$396,380.00
Summary
Cognitive dysfunction in schizophrenia is resistant to treatment and related to poor community functioning and quality of life. In spite of the widely appreciated magnitude of the problem, there is still a critical gap in our knowledge concerning treatments to reverse these cognitive deficits. The proposed research is significant because it will clarify the role of hormones and genes in relation to cognitive deficits in schizophrenia and it may help patients improve their level of functioning.
Molecular Mechanisms Of Receptor Activation And Signalling
Funder
National Health and Medical Research Council
Funding Amount
$571,980.00
Summary
Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several ....Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several hundred distinct but structurally-related members, the molecular mechanisms involved in their activation and, thus, their regulation of vital cellular functions, remains unclear. Based on insights that we have gained from the development and characterisation of several alpha1-adrenergic receptor mutants, we have developed a model of receptor activation. In this application we are proposing to further test and to extend the hypotheses underlying this model. Importantly, the functions regulated by GPCR include vital responses, such as the maintenance of circulatory homeostasis by augmenting heart pump function and by constricting vascular smooth muscle to maintain blood pressure. In addition, disordered cellular regulation by GPCR has been implicated in a wide variety of diseases, including hypertension, congestive heart failure and cardiac hypertrophy. Thus, the studies detailed here to further understand the molecular mechanisms of receptor activation have broad implications for our knowledge of critical physiological control systems, and may lead to novel therapeutic approaches to treat a variety of diseases.Read moreRead less
Developing A New Strategy For Treating Demyelinating Peripheral Diseases
Funder
National Health and Medical Research Council
Funding Amount
$496,250.00
Summary
Incomplete remyelination is a significant component of the persistent clinical disability of peripheral demyelinating neuropathy, contributing to conduction deficits and the secondary axonal damage. A crucial therapeutic challenge is to identify ways to promote remyelination. This project aims to develop a new strategy and a novel clinically relevant target for treating peripheral demyelinating neuropathy.
Pushing AR Toward Better Outcomes In Breast And Prostate Cancers
Funder
National Health and Medical Research Council
Funding Amount
$998,754.00
Summary
Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives ....Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives.Read moreRead less
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.