Robert McLachlan is an internationally recognised clinician-scientist in male reproductive health. His basic research examines the genetic & endocrine regulation of sperm production. His clinical studies span male fertility regulation, the use of assisted reproductive treatments, and the evidence-based use of androgen replacement. As Director of Andrology Australia, he has a leading national role in professional and community education, developing research capacity and male health advocacy.
Australia has an ageing population and women spend around one third of their lives after menopause. Optimising physical and emotional health at menopause is a national health priority, and improving the health of women will improve health for the community. This research program is targeted at improving physical and mental health for midlife and older women. Findings will be translated into changes in policy and practice which improve the lives of women in Australia and worldwide
The Effect Of Androgen Replacement Therapy On Bone And Muscle Health In Men With Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
Low testosterone (T) levels are common in men with poor kidney function. Low T is known to cause reduced energy, decreased strength and low libido. Normal T is also needed for healthy bones and muscles. Men with kidney disease are already at risk of fractures, poor strength and quality of life. However, there are few studies that look at replacing T to men with kidney failure. We will investigate how low T affects bone and muscle and assess how giving T can benefit bone, muscle and function.
Polycystic ovary syndrome (PCOS) affects a striking 9-21% of women of reproductive age. PCOS is an important health problem and can affect menstrual cycles, fertility and increase risk of diabetes and mood disorders. There is a lack of longitudinal studies that women with PCOS over time to examine the key determinants of PCOS, long-term impact of obesity and factors contributing to PCOS complications.
Novel Interactions Between GnRH Receptor And E2F4 Transcription Factor.
Funder
National Health and Medical Research Council
Funding Amount
$462,750.00
Summary
The reproductive endocrine system is under the control of gonadotropin-releasing hormone (GnRH), signalling via its G-protein coupled receptor (GPCR) in the anterior pituitary gland. The GnRH receptor (GnRHR) is the drug target for the treatment of a range of endocrine-related disorders as well as hormone-dependent cancers. Sustained treatment with either GnRH agonists or antagonists can block gonadotropin secretion indirectly, via down-regulation of the pituitary receptor resulting in a reducti ....The reproductive endocrine system is under the control of gonadotropin-releasing hormone (GnRH), signalling via its G-protein coupled receptor (GPCR) in the anterior pituitary gland. The GnRH receptor (GnRHR) is the drug target for the treatment of a range of endocrine-related disorders as well as hormone-dependent cancers. Sustained treatment with either GnRH agonists or antagonists can block gonadotropin secretion indirectly, via down-regulation of the pituitary receptor resulting in a reduction of gonadotropin secretion and consequent decline in steroid production. As the majority of tumours treated with GnRH analogues are hormone-dependent, this starves the tumour of the steroid support required for growth. However, the concept of a direct anti-tumour effect of GnRH, independent of the pituitary-gonadal axis, is supported by the in vitro inhibition of both cell growth and DNA synthesis in a number of tumour cell lines. Despite the wide use of GnRH analogues, the molecular basis of the growth inhibitory effects resulting from the activation of this receptor is not fully understood. Unravelling the protein interactions underlying receptor-mediated signalling events will provide valuable information towards understanding of receptor function in vivo. We have identified a novel interaction involving the GnRHR and E2F4, a transcription factor involved in suppression of the transcription of genes involved in cell cycle progression. In addition, over 80% of E2F4 knockout mice are sterile. Owing to the role of the GnRHR in the reproductive pathway we are interested in determining whether the GnRHR-E2F4 interaction has an influence on the development of the hypothalamic-pituitary-gonadal axis, hence affecting reproductive capacity. The interaction identified and studied in this proposal has implications for the treatment of reproductive tumours, such as those of the breast and prostate, and understanding the development of the hypothalamic-pituitary-gonadal axis.Read moreRead less
This fellowship will support a clinical researcher whose focus is improving metabolic and reproductive health by manipulating hormones and improving sleep. This will be achieved from a platform of NHMRC project grants and a NHMRC CCRE in interdisciplinary sleep health.
Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their ....Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their etiology, both forms result in an inability of the body to control blood sugar levels. Beta cells release the hormone insulin, which regulates blood sugar levels. Current knowledge suggests that a loss of beta cell mass is important for both diseases. For type I diabetes the beta cells are destroyed by the immune system. Though for type 2 diabetes the causes are less clear, it is apparent that the beta cells are dying. Our research is focused on understanding the molecular pathways that control beta cell survival and regulate their death. Such knowledge would help us understand the complex processes leading to the development of diabetes. Furthermore, we could use this knowledge in the design of genetic engineering strategies to create 'death-defying' beta cells, as a potential therapeutic strategy for the treatment of diabetes.Read moreRead less
Investigating Role Of Insulin Resistance And Sympathetic Nervous System In Metabolic Features Of PCOS
Funder
National Health and Medical Research Council
Funding Amount
$150,468.00
Summary
PCOS affects 9-18% of Australian reproductive aged women. Whilst reproductive features are prominent, PCOS has major psychological and metabolic consequences. Emerging data implicate the involvement of the sympathetic nervous system in PCOS. The aim of this PhD is to investigate the role of the sympathetic nervous system in insulin resistance and other metabolic features of PCOS and determine whether modification of this system's activity will favorably influence the metabolic consequences assoc ....PCOS affects 9-18% of Australian reproductive aged women. Whilst reproductive features are prominent, PCOS has major psychological and metabolic consequences. Emerging data implicate the involvement of the sympathetic nervous system in PCOS. The aim of this PhD is to investigate the role of the sympathetic nervous system in insulin resistance and other metabolic features of PCOS and determine whether modification of this system's activity will favorably influence the metabolic consequences associated with PCOS.Read moreRead less
The critical role of kisspeptin/neurokinin/dynorphin (KNDy) neurons in gonadotropin releasing hormone (GnRH) release. The brain controls fertility through the secretion of its primary stimulatory factor, gonadotropin releasing hormone (GnRH). Brain cells producing three key peptide hormones, kisspeptin, neurokin B and dynorphin (termed KNDy cells) are vital for the control of GnRH. This project will detail the role of KNDy cells in puberty and reproduction.
Androgen Receptor Signalling In Development And Progression Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$753,420.00
Summary
Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because pr ....Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because prostate cells are dependent on testicular androgens for their growth and survival, surgical or medical castration results in an initial tumour regression. However, tumours inevitably develop resistance to androgen ablation therapy and regrow. In this study we aim to provide the most comprehensive analysis to date of the role of androgen signalling in the initiation and progression of prostate cancer. This will enable us to identify the most effective means of eliminating androgen-dependent prostate tumours and identify tumours with high metastatic potential. Our studies will indicate whether treatments targeting androgen signalling are a more effective strategy to inhibit prostate cancer growth while minimising undesirable side effects.Read moreRead less