Male Reproductive Health Including Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$727,685.00
Summary
My previous contributions to Andrology and Endocrinology of the Testis provide me with a significant breadth of expertise and a sustained record of contribution to Men’s Reproductive Health. My recent research effort has focused on Urology and prostate cancer. Through my prostate cancer research program, my overall strategy is to understand the biology of the prostate gland to enable the development of new therapies for prostate cancer, as well as for BPH (enlargement of the prostate) and prosta ....My previous contributions to Andrology and Endocrinology of the Testis provide me with a significant breadth of expertise and a sustained record of contribution to Men’s Reproductive Health. My recent research effort has focused on Urology and prostate cancer. Through my prostate cancer research program, my overall strategy is to understand the biology of the prostate gland to enable the development of new therapies for prostate cancer, as well as for BPH (enlargement of the prostate) and prostatitis (inflammation of the prostate gland).Read moreRead less
Characterisation Of A Novel Prostate-expressed Kallikrein-like Protease And Its Target Proteins
Funder
National Health and Medical Research Council
Funding Amount
$724,544.00
Summary
Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones o ....Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones or androgens are known to play an important role. Prostate specific antigen or PSA has become widely accepted as a useful tool in helping to detect prostate cancer and then monitoring the disease. PSA, which is regulated by androgens, is an enzyme that either activates or breaks down many proteins that are important in both the normal function of the prostate and in the development of cancer. PSA belongs to a family of enzymes called the kallikreins. We have recently discovered a new member of this family that, like PSA, is also found in the prostate. We have called this new enzyme, K6, as it is the sixth member of this family to be identified. So , this project is about characterising this new K6 enzyme, finding out if it is also found in the prostates of men with BPH and prostate cancer, whether it is also regulated by androgens and what sort of proteins it may activate in these diseases. We will also compare these findings with what we know about PSA in these diseases. From these studies, we will not only understand more about this K6 enzyme and how it might be important in the prostate but also how it relates to PSA. These findings may ultimately lead to some new approaches in the detection and treatment for BPH and prostate cancer.Read moreRead less
Novel Functional Domains On Adrenoceptors For Drug Interaction And Cell Signalling
Funder
National Health and Medical Research Council
Funding Amount
$801,500.00
Summary
Our work involves studying cell-surface proteins (receptors) that respond to hormones such as adrenaline or substances that transmit signals in the nervous system (neurotransmitters). These receptors play a vital role in orchestrating responses to stimuli such as stress, pain, changes in blood pressure, body temperature, fluid and energy status, and exercise. They allow communication between different organs or different parts of the nervous system. G-protein coupled receptors (GPCRs) are the ma ....Our work involves studying cell-surface proteins (receptors) that respond to hormones such as adrenaline or substances that transmit signals in the nervous system (neurotransmitters). These receptors play a vital role in orchestrating responses to stimuli such as stress, pain, changes in blood pressure, body temperature, fluid and energy status, and exercise. They allow communication between different organs or different parts of the nervous system. G-protein coupled receptors (GPCRs) are the major group of cell surface receptors that interact with hormones and neurotransmitters. Treatment of many diseases and conditions relies on the use of drugs that selectively activate or block a single type of GPCR. In fact, about 2-3 of existing therapies are based on these drugs. In designing new drugs it is important to understand as much as possible about the properties of the target receptors. There is emerging evidence concerning interactions between drugs, receptors and proteins inside cells that translate signals into responses (signalling proteins). For example, receptors have additional sites of drug action that can modulate their activity, and can also couple to multiple signalling pathways. We are studying adrenoceptors that respond to adrenaline and to the neurotransmitter noradrenaline. Our studies will use adrenoceptors as model systems to identify novel potential sites for drug interaction, to gain new insights into signalling mechanisms utilized by these receptors and to examine how a variety of phosphorylation mechanisms affect the ability of receptors to couple to particular signalling pathways.Read moreRead less
Hormonal Modulation Of Prostatic Growth And Contractility
Funder
National Health and Medical Research Council
Funding Amount
$324,237.00
Summary
With increasing age human males are likely to develop benign prostatic hyperplasia (BPH), a disorder characterized by urethral obstruction due to an increase in size of the prostate gland. Drug treatments of this condition are not entirely satisfactory and the current project is to examine the mechanisms by which the prostate grows and occludes the urethra. We will use human prostate cells grown in artificial conditions to determine which hormones alter the types of cells and especially examine ....With increasing age human males are likely to develop benign prostatic hyperplasia (BPH), a disorder characterized by urethral obstruction due to an increase in size of the prostate gland. Drug treatments of this condition are not entirely satisfactory and the current project is to examine the mechanisms by which the prostate grows and occludes the urethra. We will use human prostate cells grown in artificial conditions to determine which hormones alter the types of cells and especially examine those cells which can contract as these may be of critical importance in the urethral obstruction. We hypothesize that an enzyme called protein kinase C may be implicitly involved in both cell growth and contractile function and we will examine the role of protein kinase C with a view ultimately to develop drugs which may interfere with this process and therefore aid in non-surgical treatment of the condition.Read moreRead less
Selectivity And Mode Of Action Of Rho-conopeptide TIA: A Novel Inhibitor Of Alpha1-adrenoceptors.
Funder
National Health and Medical Research Council
Funding Amount
$399,300.00
Summary
A major obstacle to the development of safer and more effective treatments for cardivascular diseases and benign prostatic hyperplasia is the inability to find small molecules with sufficient specificity to be safe and effective. The applicant team brings together a unique set of complementary research interests and skills in using conotoxins to define, at the molecular level, how rho-conotoxins act at the alpha1-adrenoceptor, a major drug target for cardiovascualr and related diseases. Rho-cono ....A major obstacle to the development of safer and more effective treatments for cardivascular diseases and benign prostatic hyperplasia is the inability to find small molecules with sufficient specificity to be safe and effective. The applicant team brings together a unique set of complementary research interests and skills in using conotoxins to define, at the molecular level, how rho-conotoxins act at the alpha1-adrenoceptor, a major drug target for cardiovascualr and related diseases. Rho-conotoxins are novel peptide inhibitors of the alpha1-adrenoceptor that appear to act at an undescribed allosteric site. This Project will use rho-conotoxins and analogues to characterise structurally and functionally how and where this class of conopepides act. The structure activity relationship for rho-conotoxins will be established to guide the development of subtype specific inhibitors. Pairwise interactins between the alpha1-adrenoceptorand TIA will be used to dock TIA onto a homolgy model of the alpha1-adrenoceptor. The long-term goal of the project is to develop new and safer treatments for cardiovascular and related disorders.Read moreRead less
The Role Of Ghrelin And Growth Hormone Releasing Hormone In The Autocrine Regulation Of Prostate Cancer Cell Growth
Funder
National Health and Medical Research Council
Funding Amount
$240,990.00
Summary
Insulin-like growth factor-I (IGF-I) is an important growth factor with a major role in the growth and development of many normal and tumour cells. Its production is controlled by growth hormone (GH), released from the pituitary gland at the base of the brain. GH releasing hormone (GHRH), a hormone released from higher centres in the brain, regulates the production of GH itself and now it is recognised that a second pathway, the ghrelin-GH secretagogue receptor (GHS-R) axis is also important in ....Insulin-like growth factor-I (IGF-I) is an important growth factor with a major role in the growth and development of many normal and tumour cells. Its production is controlled by growth hormone (GH), released from the pituitary gland at the base of the brain. GH releasing hormone (GHRH), a hormone released from higher centres in the brain, regulates the production of GH itself and now it is recognised that a second pathway, the ghrelin-GH secretagogue receptor (GHS-R) axis is also important in regulating GH release. There is growing evidence that the GHRH-GH-IGF axis has a significant role in prostate cancer, but little is known about how this happens. We also have evidence that the ghrelin-GHS-R axis is involved in prostate cancer, as prostate cancer cell lines produce both ghrelin and the receptor through which it acts. Our preliminary studies show that ghrelin enhances cell growth in these cells. GHRH blocking agents (antagonists) are potential treatments for prostate cancer, as they slow the growth of prostate tumours. How they act is unclear, but they might interfere with a locally active GHRH pathway in the prostate. This study aims to explore the role of ghrelin and GHRH in prostate cancer. Since there is an increase in the use of GHRH, GH and-or IGF-I and potentially ghrelin for the treatment of a variety of medical conditions, including some in the aging male, the need for a fuller understanding of the role of this axis in prostate cancer is increasingly important. Such information will lead to a deeper understanding of the actions of ghrelin and GHRH and provide potential opportunities for design of new therapies for prostate and other GH-IGF-responsive tumours.Read moreRead less
Role Of Pacemaker Cells In The Generation Of Slow Wave Activity In The Prostate Gland
Funder
National Health and Medical Research Council
Funding Amount
$231,500.00
Summary
The prostate gland commonly enlarges in ageing males resulting in a condition known as benign prostatic hyperplasia which is poorly understood. Because of the strategic position of the prostate, its enlargement physically compresses the segment of the urinary system passing through it causing inconvenient and distressing symptoms, such as difficulty and hesitancy in urination, which often require surgical or medical intervention. Indeed patients diagnosed with benign prostatic hyperplasia are of ....The prostate gland commonly enlarges in ageing males resulting in a condition known as benign prostatic hyperplasia which is poorly understood. Because of the strategic position of the prostate, its enlargement physically compresses the segment of the urinary system passing through it causing inconvenient and distressing symptoms, such as difficulty and hesitancy in urination, which often require surgical or medical intervention. Indeed patients diagnosed with benign prostatic hyperplasia are often treated with pharmacological agents that reduce the size of the prostate or relax the prostate and bladder, thus relieving some of the symptoms. However, the precise cellualr mechanisms by which many of these drugs mediate their effects have not been confirmed. Moreover, although previous studies of the prostate gland have clearly established many of the basic properties of the tissue, there is currently a lack of information regarding the prostate gland at a cellular level. We have recently identified a specialised group of 'interstitial cells' in the prostate gland, which resemble the well-described 'interstitial cells of Cajal' in the gut. In the gut, these cells perform a wide variety of functions including the initiation of contractile activity. Interstitial cells are also thought to play a role in diseases of the bowel. This project aims to investigate the role of the interstitial cells in the functioning of the prostate gland. In addition, the effects of age and hormones on the interstitial cells will be considered, which may lead to a better understanding of conditions such as benign prostatic hyperplasia. Finally, identifying nerve-released substances that may affect the activity of these cells may also help identify alternative targets for treatment of benign prostatic hyperplasia.Read moreRead less
Ontogeny Of The Airway Smooth Muscle Layer In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$535,914.00
Summary
In asthmatic patients the thickness of the airway smooth muscle (ASM) layer is increased early in life and even before doctor-diagnosis. An intriguing possibility is our overarching hypothesis that the ASM layer is thickened from birth and represents an independent risk factor for the development of asthma. This project strives to understand better how the ASM layer matures from late gestation to adulthood and whether abnormal maturation contributes to disease susceptibility.