Gastrointestinal Function And Appetite In Obesity - Acute And Longer-term Effects Of Changes In Energy Intake
Funder
National Health and Medical Research Council
Funding Amount
$744,645.00
Summary
The prevalence of obesity is assuming epidemic proportions. While weight loss diets help people to lose weight, body weight stabilises over time despite continued dieting. Our research proposal represents a novel initiative with the aim to understand the adaptations in gastrointestinal mechanisms in response to acute and longer-term dietary restriction that compromise weight loss. Ultimately our research will help to develop weight loss strategies that are successful in the long-term.
Intestinal Adaptation Following Massive Small Intestinal Resection: Mechanisms And Management
Funder
National Health and Medical Research Council
Funding Amount
$256,980.00
Summary
Short bowel syndrome (SBS) remains a major clinical problem in paediatric and adult clinical practice. The Department of Gastroenterology and Clinical Nutrition at the Royal Children's Hospital has gained recognition as a national centre of excellence for the management of infants and children with SBS and intestinal failure. Due to the significant personal and heath-care burden related to SBS there has been an urgent need to improve understanding about the process of intestinal adaptation follo ....Short bowel syndrome (SBS) remains a major clinical problem in paediatric and adult clinical practice. The Department of Gastroenterology and Clinical Nutrition at the Royal Children's Hospital has gained recognition as a national centre of excellence for the management of infants and children with SBS and intestinal failure. Due to the significant personal and heath-care burden related to SBS there has been an urgent need to improve understanding about the process of intestinal adaptation following massive small bowel resection (MSBR) in order to develop new treatments aimed at improving clinical outcome for patients with SBS. Over the past 5 years we have developed a preclinical model for the study of intestinal adaptation in infants using the juvenile pig. Our recent studies in this model have revealed that elemental formula is inferior to whole protein formula suggesting that the current clinical recommendations need urgent re-evaluation. Using the preclinical model in this proposal, we aim to define the mechanisms underlying the adaptive response and evaluate novel therapies aimed at enhancing adaptation following MSBR. Supplementation of enteral feeds with bovine colostrum isolate resulted in normal growth in the preclinical model despite MSBR. In this proposal we plan to advance this observation for the first time to human clinical trials in infants with SBS. Even small gains in enteral tolerance during the early post-operative period may have a significant impact on morbidity and mortality of children with SBS due to parenteral-nutrition related liver disease and gut-related sepsis. This research proposal provides a unique link between studies aimed at providing the scientific basis for understanding the mechanisms of intestinal adaptation using an established preclinical model and translating the results of these studies onto human trials, taking advantage of the clinical expertise available in the management of children with SBS.Read moreRead less
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.