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
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.
Hypoxic Regulation Of Integrin Beta1 During Mucosal Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$318,104.00
Summary
Very little is currently known about how healing is initiated in the gut. Further understanding may allow us to improve the treatment of IBD wounding and allow new therapies to control the disease. Our work examines the role of an adhesion protein, ?1 integrin, important in the repair of intestinal wounds. Understanding the mechanisms of how ?1 integrin is involved in wound healing may allow the rational design of therapies to aid or accelerate wound healing in inflammatory disease.
Novel Epigenetic And Molecular Determinants Of Gastric Cancer Initation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$432,909.00
Summary
Over one million deaths from stomach cancer occur annually. This often fatal disease can be caused by infection with the bacterium H. pylori. I am a molecular biologist seeking to understand how inflammation caused by H. pylori drives a genetic signature which can be used to predict stomach cancer risk. I will also study how a new family of stomach proteins can prevent tumour growth. My research aims to lead new initiatives for early detection and treatment of stomach cancer.
Gastrokine 2 Promotes Gastric Homeostasis And Inhibits Bacterial Pathology
Funder
National Health and Medical Research Council
Funding Amount
$621,335.00
Summary
Gastrokine 2 is a small regulatory protein secreted by the stomach lining. Its function is unknown but data from our lab suggests that it may be important in maintaining stomach integrity. This project will investigate how gastrokine 2 maintains stomach function, how this can be compromised when bacterial infection is ongoing, and how we might be able to turn up gastrokine 2 expression to prevent inflammation and precancerous changes in the stomach lining.
Interferon Regulatory Factor 6: A Novel Epithelial-specific Regulator Of Mucosal Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$517,989.00
Summary
Epithelial cells lining the respiratory and gastrointestinal tracts play pivotal roles in protecting us from infection. Inflammatory factors released by epithelial cells are important for fighting infection; however, they also contribute to chronic inflammatory diseases. We aim to understand how a protein called IRF6 regulates the inflammatory response of epithelial cells. The knowledge gained will identify new therapeutic approaches for inflammatory diseases.
A Novel Therapeutic Target For Preventing Helicobacter Pylori-associated Diseases
Funder
National Health and Medical Research Council
Funding Amount
$750,336.00
Summary
Gastric cancer mainly results from chronic inflammation (gastritis) caused by the stomach-dwelling bacterium, Helicobacter pylori. We have identified a potassium channel which our data suggest could be a new therapeutic target for protecting against gastric cancer caused by H. pylori infection. This project will test the role of this channel in H. pylori gastritis and see whether drugs that target this channel can protect mice against H. pylori-associated disease.
Therapeutically Exploiting Non-oncogene Addiction And Defining Genetic Interactions For Disease Progression In A Preclinical Model Of Inflammation-dependent Gastric Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$624,960.00
Summary
Cancers of the stomach are often associated with chronic inflammation and represent a major health burden with little treatment options available. We propose to test whether drugs undergoing clinical testing for other diseases may have beneficial effects in a preclinical model of gastric cancer, and establish the genetic interaction required for gastric cancer progression. The study outcomes may highlight novel therapeutic opportunities for the clinic.
Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. Most bacterial and viral pathogens enter the body via mucosal tissues. We have recently demonstrated that mucin proteins are a vital component of initial defence against mucosal pathogens. Defects in these proteins probably predispose individuals to common chronic infective and inflammatory diseases. T ....Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. Most bacterial and viral pathogens enter the body via mucosal tissues. We have recently demonstrated that mucin proteins are a vital component of initial defence against mucosal pathogens. Defects in these proteins probably predispose individuals to common chronic infective and inflammatory diseases. The proposed research aims to explore the mechanims by which mucins protect from infection, with a focus on the gastrointestinal tract. Gastrointestinal infections remain one of the major causes of mortality in children in undeveloped countries. We believe that these proteins are a critical hereto unrecognised element of immunity and that the proposed studies will have broad significance for treatment and prevention of infection. Additionally, understanding the function of mucins could lead to the development of new drugs to treat epithelial inflammation such as that seen in inflammatory bowel diseases and respiratory diseases such as asthma and cystic fibrosis.Read moreRead less
Microtubule Capture By E-cadherin: A Novel Mechanism For Dynamic Cell-cell Adhesion.
Funder
National Health and Medical Research Council
Funding Amount
$439,500.00
Summary
This project studies the molecular mechanisms responsible for holding cells together in normal tissues. Such cell-to-cell adhesion is mediated by the cadherin family of molecules, which reside at the surfaces of cells. Cadherins allow cells to recognize one another and, upon recognition, adhere to one another. By this means populations of individual cells can be linked together into cohesive populations (i.e. the tissues or organs of the body). The importance of cadherin adhesion is exemplified ....This project studies the molecular mechanisms responsible for holding cells together in normal tissues. Such cell-to-cell adhesion is mediated by the cadherin family of molecules, which reside at the surfaces of cells. Cadherins allow cells to recognize one another and, upon recognition, adhere to one another. By this means populations of individual cells can be linked together into cohesive populations (i.e. the tissues or organs of the body). The importance of cadherin adhesion is exemplified by the well-documented observation that disruption of cadherin adhesion contributes to many important diseases, including inflammation of epithelia and cancers. Thus understanding the mechanisms by which cadherins hold cells together is necessary for us to understand the molecular basis of commondisease. It has long been known that cadherins work in cooperation with elements within the cell, called the cytoskeleton. My lab has recently made the novel discovery that microtubules, specific components of the cytoskeleton, can regulate the functionof cadherin adhesion molecules. Inparticular, microtubules appear to affect how cadherins can participate in dynamic cell processes necessary for cells to be properly organized in tissues. In this project we will probe the molecular mechanisms responsible for this effect of microtubules. The information obtained will provide important new insights into how dynamic cadherin adhesion is controlled, to help our understanding of the cellular mechanisms that couple cells into tissues, and how they may be disrupted in diesase.Read moreRead less