The Role Of A Low Emulsifier Diet To Treat Crohn's Disease
Funder
National Health and Medical Research Council
Funding Amount
$447,603.00
Summary
Currently, there are no specific diets known to treat Crohn’s disease (CD). Initial lab- and animal-based studies have indicated emulsifiers added to food drive inflammation in CD, but no human trials completed. This study will design and feed high and low emulsifier diets to healthy and CD subjects and measure markers of inflammation. This will establish the role of a low emulsifier diet to treat CD.
Genetic Validation Of Stat3 As A Tractable Pharmacological Target In Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$586,964.00
Summary
Cancers of the stomach and the colon are a major health burden. One of the central signaling molecules that drives these cancers is called Stat3. Here we propose to use a novel strain of mice that allows us to experimentally dial down the amount of Stat3 protein and hence to predict how effective a future anti-Stat3 cancer drug will be.
Bacterial pathogens are a major cause of illness and death, producing diseases ranging from acute infections to cancer. However, not all infected individuals will succumb to these pathologies. What factors dictate which individuals develop these diseases is an important complex question. The core focus of my research is the identification and characterisation of novel host factors that are involved in resistance or susceptibility to bacterial-associated diseases of the gastrointestinal tract.
Regulation Of Cellular Responses To Neuropeptides.
Funder
National Health and Medical Research Council
Funding Amount
$83,510.00
Summary
Neuropeptides are chemicals released from nerves that are responsible for communication between the nerves, glands, muscles or other nerves. Neuropeptides exert their diverse biological effects by interacting with small structures on the cells they wish to communicate with. These structures bind the neuropeptide and are termed neuropeptide receptors. The responses of tissues to neuropeptides, for example, contraction of muscle, decrease with continued exposure to the neuropeptide. This reduction ....Neuropeptides are chemicals released from nerves that are responsible for communication between the nerves, glands, muscles or other nerves. Neuropeptides exert their diverse biological effects by interacting with small structures on the cells they wish to communicate with. These structures bind the neuropeptide and are termed neuropeptide receptors. The responses of tissues to neuropeptides, for example, contraction of muscle, decrease with continued exposure to the neuropeptide. This reduction in response is termed desensitization is thought to turn off the response to cells following stimulation by neuropeptides. In this study, I will investigate the mechanisms behind the desensitization of VPAC receptors which are a found throughout the body and have many important roles for example, gastrointestinal, pancreatic and reproductive function and control of muscle. VPAC receptors are also highly expressed in certain many cancers such as breast, prostate and colon carcinoma. The wide variety of functions that these receptors perform and the wide distribution in the body suggest that these are very important receptors. To date research into the responses and desensitisation of these receptors has been lacking, and the work that has been done has become confusing as more receptors and neuropeptides which bind them are discovered. The current project aims to carefully study these receptors and to determine their role in health and disease. The understanding the interaction of receptor and neuropeptide can perhaps lead to development of new therapeutic agents.Read moreRead less
Pancreatic Cancer is the fourth leading cause of cancer death in men and women in Western societies. Nothing, apart from surgery in a small proportion of individuals gives any hope. The identification of novel treatment strategies in the modern era necessitates a rational scientific approach, where an understanding of the molecular mechanisms involved in the evolution of cancer underpins the development of such strategies in an efficient manner. Retinoids are derivatives of Vitamin A, and have b ....Pancreatic Cancer is the fourth leading cause of cancer death in men and women in Western societies. Nothing, apart from surgery in a small proportion of individuals gives any hope. The identification of novel treatment strategies in the modern era necessitates a rational scientific approach, where an understanding of the molecular mechanisms involved in the evolution of cancer underpins the development of such strategies in an efficient manner. Retinoids are derivatives of Vitamin A, and have been used extremely successfully in the treatment of some leukaemias. Unfortunately, retinoids have not worked as well in other cancers. We have identified an important role for abnormal retinoid function in the evolution of pancreatic cancer, which may be responsible for the lack of effective response to retinoid treatment. This project focuses on identifying if these abnormalities in retinoid function can be reversed with adding specific pharmaceuticals so that retinoid based therapies will be effective in pancreatic cancer.Read moreRead less
Gut motility requires enteric neurons, which are located in the gut wall. During development, enteric neurons arise from precursors in the brain that migrate into the intestine. Failure of enteric neuron precursors to migrate and differentiate normally results in pediatric motility disorders. The aim of this research is to identify the mechanisms controlling the development of enteric neurons so that therapies can be developed for pediatric motility disorders.
Inflammation Drives TFF2 Epigenetic Silencing In Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$618,909.00
Summary
Over one million deaths from stomach cancer will occur annually in the next decade. This often fatal disease can be caused by infection from childhood by the bacterium H. pylori. We will study a new link between the inflammation caused by H. pylori and a type of mutation known as epigenetic silencing that switches off a gene which normally prevents stomach cancer. Understanding this process will help us to discover approaches for early detection of stomach cancer and lead to the development of n ....Over one million deaths from stomach cancer will occur annually in the next decade. This often fatal disease can be caused by infection from childhood by the bacterium H. pylori. We will study a new link between the inflammation caused by H. pylori and a type of mutation known as epigenetic silencing that switches off a gene which normally prevents stomach cancer. Understanding this process will help us to discover approaches for early detection of stomach cancer and lead to the development of new drugs that prevent disease.Read moreRead less
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.
Chronic Gastrointestinal Symptoms And Diabetes Mellitus: Risk Factors And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$271,527.00
Summary
Why many people with diabetes mellitus are afflicted by gastrointestinal (GI) symptoms remains uncertain. Irreversible damage to the nerves controlling the gut (autonomic neuropathy) is often considered to be important. An alternative cause of increased GI symptomatology in diabetics is poor glucose control. Some studies have shown that acute shifts in glucose levels induce changes in the gut relevant to the onset of GI symptoms. For example, high glucose levels acutely cause slower stomach empt ....Why many people with diabetes mellitus are afflicted by gastrointestinal (GI) symptoms remains uncertain. Irreversible damage to the nerves controlling the gut (autonomic neuropathy) is often considered to be important. An alternative cause of increased GI symptomatology in diabetics is poor glucose control. Some studies have shown that acute shifts in glucose levels induce changes in the gut relevant to the onset of GI symptoms. For example, high glucose levels acutely cause slower stomach emptying times, leading to feelings of fullness. Though the effects of chronic glucose levels are yet to be properly explored, population data show that poor control in the long-term is related to an increase in symptoms. The aim of this prospective study is to determine the roles played by both autonomic neuropathy and glucose control in the development of GI symptoms among diabetics. All past research has been cross-sectional, and so cannot tell us if one or both of these factors cause GI problems in diabetes. For example, it is possible that autonomic neuropathy causes an increase in GI symptoms such as nausea and fullness, which in turn induces poor glucose control though lack of appetite or inadequate stomach emptying. Upon study inclusion, all study participants will undergo a series of autonomic tests. At 3 month intervals for a period of 30 months, they will be asked to complete a 2-week diary card detailing their GI symptoms and glucose readings, and also supply blood and urine samples for analysis twice each year. Two years from the study outset, participants will again complete the autonomic test series. Psychiatric co-morbidity will be investigated using the Composite Diagnostic Interview (CIDI-Auto) at the autonomic testing time points. The study will be undertaken at the Gastroenterology Research Unit at Nepean Hospital, in collaboration with the Royal Adelaide Hospital, centres with proven track records in diabetes investigation.Read moreRead less
Pesonalised Risk Prediction For Severe Treatment-related Gastrointestinal Toxicity In Paediatric Cancer Patients Using Pre-treatment Gut Microbiome Analysis
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
The gut is home to trillions of good and bad bacteria, critical to human health. Each person has a different balance of bacteria, unique to their gut, which shapes their immune system and susceptibility to disease. I will investigate how the unique gut bacteria, in children with blood cancer, can be used to predict which children will develop severe gut side effects (diarrhoea) from their chemotherapy. This will identify high-risk children, enable personalised treatment and improve survival.