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
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
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
Understanding The Opposing Roles Of SWI-SNF In The Control Of Gene Programs For Pathological Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$476,258.00
Summary
Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression.
Transcriptional Regulatory Complexes Associated With Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$474,517.00
Summary
Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression. It has been well known that a group of genes are altered (up or down) in the heart under conditions such as heart muscle overgrowth (ie ....Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression. It has been well known that a group of genes are altered (up or down) in the heart under conditions such as heart muscle overgrowth (ie hypertrophy), aging or of abnormal beating function. The reasons for such altered gene activity remain poorly understood. Although recent studies from research on genetics or cancer have revealed the important role of the DNA and DNA-bound proteins (called histone) in the control of gene activity, this has rarely been studied in the heart. In this project, we will test our hypothesis that DNA-histone structure is a key factor that control gene activities in ageing and diseased heart. This proposal is supported by our recent findings showing that in the hypertrophied heart, such DNA-histone structure did alter in such a way that fits well with alterations in gene activity. We have planned a series of studies to test this hypothesis in a systematic fashion. A number of sophisticated and cutting-edge techniques and experimental models of heart hypertrophy will be used. We will analyse changes in activities of a number of selected genes in the heart and also analyse changes in DNA-histone structures and chemical modifications at particular regions. These changes will then be linked together. We will also explore the possibility of modulating DNA-histone structure, thereby controlling the degree of cardiac hypertrophy. This project is the joint efforts of scientists with substantial experience in research on gene activity and heart diseases, and is highly likely to generate novel information to and hold significant therapeutic potential.Read moreRead less
Structural And Functional Consequences Of Left Ventricular Hypertrophy Regression.
Funder
National Health and Medical Research Council
Funding Amount
$293,036.00
Summary
Left ventricular hypertrophy (LVH) is a thickening of the heart muscle walls that occurs in a variety of cardiovascular diseases, including high blood pressure, coronary artery disease, cardiac valve disorders and heart dilatation. The presence of LVH increases the risk of developing heart attacks, heart failure and death. Treatment of these disorders is a major component of our escalating health-care costs. Consequently, reversal of LVH may have significant benefits to individual patients and s ....Left ventricular hypertrophy (LVH) is a thickening of the heart muscle walls that occurs in a variety of cardiovascular diseases, including high blood pressure, coronary artery disease, cardiac valve disorders and heart dilatation. The presence of LVH increases the risk of developing heart attacks, heart failure and death. Treatment of these disorders is a major component of our escalating health-care costs. Consequently, reversal of LVH may have significant benefits to individual patients and society in general. We propose to develop a mouse model of an inherited form of LVH that is caused by gene mutations in heart muscle proteins. This model will enable us to study in detail the disease processes that cause LVH and the effects of reversing LVH. This information will be invaluable for determining the best ways of treating patients with LVH.Read moreRead less