I am a physiologist with expertise in endocrinology determining the roles of particular regulatory peptides in the normal functions of the gastrointestinal tract and in the development of gastrointestinal, renal and prostate cancers.
Understanding The Structure/function Relationships Of The Iron Regulatory Peptide Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$365,126.00
Summary
This project seeks to understand the interactions between the peptide hormone hepcidin and its receptor and use this information to develop new drugs. Hepcidin is the major iron-regulatory hormone in humans and a range of iron-related diseases are caused by incorrect levels of this hormone. Many Australians are affected by these diseases so the development of hepcidin-based treatments has the potential to have significant impact on the overall health of the community.
Relaxin family peptides are small proteins that have numerous essential biological roles in the vascular system, brain and gut. The hormone relaxin is currently in Phase III clinical trials to treat heart failure and the other peptides show great potential as drugs to treat diseases including mental illnesses and obesity. My research focuses on developing drugs targeting the receptors for these important peptide systems and understanding how these drugs can be best used therapeutically
Roles For Gastrin And Hypoxia In Colorectal Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$636,508.00
Summary
Our objective is to understand how hormones such as gastrin stimulate the development of colorectal cancer. Our preliminary data shows that the amount of gastrin produced by tumour cells is increased by low oxygen. We will therefore study how the increase in gastrin in response to low oxygen causes a compensatory growth of the tumour. The ability to interfere with this process should allow us to slow tumour growth.
Determining Modes Of Binding And Activation Of Peptide G-protein Coupled Receptor Targets
Funder
National Health and Medical Research Council
Funding Amount
$576,538.00
Summary
The neuropeptide relaxin-3 and the peptide hormone INSL5 are recently discovered members of the relaxin peptide family. Relaxin-3 has important roles in stress and feeding whereas INSL5 is a gut hormone. We will study the interaction of relaxin-3 and INSL5 with their cell surface receptors and the mechanisms by which the receptors function. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin-3 and INSL5 for future clinical applications
Progastrin Derived Peptides: Biological Activities And Functions In The Gastrointestinal Tract
Funder
National Health and Medical Research Council
Funding Amount
$454,500.00
Summary
Gastrin is a hormone from the stomach which aids digestion by stimulating acid secretion. However too much acid can cause ulcers of the gastrointestinal tract. Gastrin also stimulates the growth of the lining of the stomach and intestines. This growth promoting effect is important for the development of the gastrointestinal tract before birth and may also be involved in a number of cancers especially colon cancer. Several different forms of gastrin are made by endocrine cells of the stomach and ....Gastrin is a hormone from the stomach which aids digestion by stimulating acid secretion. However too much acid can cause ulcers of the gastrointestinal tract. Gastrin also stimulates the growth of the lining of the stomach and intestines. This growth promoting effect is important for the development of the gastrointestinal tract before birth and may also be involved in a number of cancers especially colon cancer. Several different forms of gastrin are made by endocrine cells of the stomach and by cancers of the colon. It seems that the different types of gastrins have different effects and act through distinct receptors, but we do not know which are the most important forms and whether all forms are biologically active. The amount, type and activity of the different gastrins, and the regions of the molecule that are essential for biological activity, will be investigated using cell lines, animal models that overproduce too much gastrin, animal models of colon cancer and in patients with colon cancer. Colorectal carcinoma (cancer of the large bowel) is the second most common cause of cancer death. A successful outcome will result in the development of assays for the early diagnosis and monitoring of bowel cancer and the potential for novel treatments such as gastrin receptor antagonists and radiolabelled gastrin analogues for radiotherapy.Read moreRead less
Detecting Bioactivity In A Naturally-occurring Aggrecan Fragment
Funder
National Health and Medical Research Council
Funding Amount
$407,634.00
Summary
The dynamic balance of anabolic and catabolic processes in healthy cartilage is disturbed in arthritis, with increased catabolism leading to irreparable cartilage damage. We will study the ability of a naturally-occuring aggrecan fragment to modulate cartilage catabolism. Our in vitro and in vivo experiments suggest that the aggrecan fragment limits cartilage destruction. This study tests our hypothesis that the aggrecan fragment antagonises cartilage damage and promote cartilage repair.
Development Of A Generic Strategy For The Stabilisation Of Peptide-based Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$443,196.00
Summary
There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. However, there are still a number of hurdles that need to be overcome before this source of promising pharmaceuticals can fulfil their vast potential. One of the biggest challenges in the development of peptides and proteins as drugs is overcoming their poor stability in the human body. The broad aim of this research proposal is to develop a novel strategy that provides the ....There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. However, there are still a number of hurdles that need to be overcome before this source of promising pharmaceuticals can fulfil their vast potential. One of the biggest challenges in the development of peptides and proteins as drugs is overcoming their poor stability in the human body. The broad aim of this research proposal is to develop a novel strategy that provides therapeutically promising peptides and proteins the ability to resist the body s natural degradation pathways so they are able to reach their biological target. To develop this strategy we will use the recently discovered peptide hepcidin as a model system. Hepcidin is the major iron-regulatory hormone in the human body and incorrect levels of this hormone result in either iron overload (haemochromatosis), when there is not enough hepcidin produced by the body, or anemia of inflammation when there is too much hepcidin. The development of hepcidin-based therapeutic agents to treat these conditions has the potential to have significant impact as it has been estimated that up to 1 in 300 Australians are affected by haemochromatosis during their lifetimes. Unfortunately, unmodified peptides, like hepcidin, are of limited therapeutic value due to their poor stability within the human body. This research proposal describes the development of stabilised hepcidin analogues with the potential of being useful drug leads for the treatment of haemochromatosis.Read moreRead less
Unravelling The Binding And Activation Mechanism Of A Complex G Protein-coupled Receptor
Funder
National Health and Medical Research Council
Funding Amount
$1,041,638.00
Summary
The peptide hormone relaxin is currently in a Phase III trial for the treatment of heart failure. However the peptide is not a good drug as it can't be taken orally and is very expensive to produce. We will study the interaction of relaxin with its cell surface receptor and the mechanisms by which the receptor functions. The knowledge gained will aid in the design of smaller, more potent and orally active forms of relaxin for the treatment of heart failure