Dissecting The Role Of The Adipokine Leptin In Control Of The Inflammatory Response To Helicobacter Pylori
Funder
National Health and Medical Research Council
Funding Amount
$569,063.00
Summary
Helicobacter pylori is a bacterium that causes chronic gastric inflammation (gastritis), which may lead to cancer. Approximately 20% of Australians are infected. As part of the search for a human vaccine, we are attempting to understand the immune response against this bacterium. This study will investigate a novel observation that adipokines-small proteins produced by fat cells can regulate the actions of immune cells in the stomach and in this way determine whether vaccination works.
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.
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.
Generation Of Induced Pluripotent Stem (iPS) Cells And Their Potential Use In Periodontal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$798,350.00
Summary
Dental diseases affecting the gums (periodontal diseases) are extremely prevalent. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised chewing function. If left untreated, the associated loss of function may necessitate extraction of the teeth. We propose to generate induced pluripotent stem cells from gums and explore whether they can be used to restore periodontal tissues damaged by periodontal disease.
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.
Identification Of Novel Colonisation Factors In Helicobacter Pylori
Funder
National Health and Medical Research Council
Funding Amount
$336,142.00
Summary
The discovery by Drs Marshall and Warren of the bacterium Helicobacter pylori, and its role in stomach disease, has proven to be one of the major break-throughs of the late 20th century. Indeed, several common ailments of the upper digestive tract that were once thought to be untreatable, or which could only be treated by radical surgery, are now managed through the use of antibiotics and acid-blocking substances. The efficacy of these treatments has, however, been affected by the increasing rat ....The discovery by Drs Marshall and Warren of the bacterium Helicobacter pylori, and its role in stomach disease, has proven to be one of the major break-throughs of the late 20th century. Indeed, several common ailments of the upper digestive tract that were once thought to be untreatable, or which could only be treated by radical surgery, are now managed through the use of antibiotics and acid-blocking substances. The efficacy of these treatments has, however, been affected by the increasing rates of H. pylori resistance to these antibiotics in the general community. Furthermore, the limited choice of antibiotics available for use in anti-H. pylori treatment regimens, and the side-effects associated with several of these compounds, suggest that there is a need to develop new therapies against this bacterial infection. This, however, will necessitate a greater understanding of the mechanisms by which H. pylori is able to colonise and survive in the mucus layer covering the stomach. To address this point, we have used a gene profiling technique to compare gene expression in H. pylori bacteria displaying high and low levels of colonisation in a mouse model. For this, mouse-colonising H. pylori bacteria were attenuated through extensive passaging on culture media in the laboratory. Five genes were identified as being poorly expressed in the attenuated bacteria. These genes are proposed to encode putative H. pylori colonisation factors. The aim of the project is to characterise these factors, and to determine the roles of two of these, which are involved in the production of vitamin B6, in the colonisation of the stomach. This work will contribute to a greater understanding of the factors involved in H. pylori colonisation of the stomach. Amongst the possible public health benefits of this work is the identification of molecular targets for the development of new therapies for the prevention and treatment of H. pylori infection.Read moreRead less
The Significance Of Aeroallergens In Eosinophilic Esophagitis
Funder
National Health and Medical Research Council
Funding Amount
$117,331.00
Summary
Eosinophilic esophagitis is an allergic condition that causes difficulty swallowing food and chest discomfort.Current diagnostic methods are inaccurate, and treatments are not curative. This project aims to clarify the role of promising new diagnostic techniques and to delineate the significance of aeroallergens (e.g. pollens) with a view to improving the treatment of eosinophilc esophagitis in the future. It is possible that simply avoiding pollens or treating hayfever in the future may be all ....Eosinophilic esophagitis is an allergic condition that causes difficulty swallowing food and chest discomfort.Current diagnostic methods are inaccurate, and treatments are not curative. This project aims to clarify the role of promising new diagnostic techniques and to delineate the significance of aeroallergens (e.g. pollens) with a view to improving the treatment of eosinophilc esophagitis in the future. It is possible that simply avoiding pollens or treating hayfever in the future may be all that is required to manage this condition.Read moreRead less
Towards Alternative Therapeutic Agents To Antibiotics For The Treatment Of Helicobacter Pylori Infections.
Funder
National Health and Medical Research Council
Funding Amount
$787,286.00
Summary
The bacterium H. pylori, is the leading cause of gastric ulcers, infecting over half of the world population. Furthermore, patients infected with the bacteria exhibit an increased risk of developing gastric cancer, with 900,000 new cases diagnosed yearly. The current proposal will study an enzyme which allows the bacterium to evade the host's immune system. The work aims to develop inhibitors of the enzyme as therapeutic agents to treat peptic ulcers.
A Prospective Single Arm Trial Of Involved-field Radiotherapy For Stage I-II Low Grade Nongastric Marginal Zone Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$363,869.00
Summary
This is an international, multicentre study that will, for the first time, prospectively measure the curative potential of radiotherapy in localised marginal zone lymphoma (MZL). Most MZL arises in mucosa-associated lymphoid tissue (MALT), either in the stomach or in a range of other organs such as salivary glands, the tissues around the eye or the thyroid. Many stomach MALT lymphomas are caused by infection with Helicobacter Pylori. This infection can also be associated with non-gastric MALT ly ....This is an international, multicentre study that will, for the first time, prospectively measure the curative potential of radiotherapy in localised marginal zone lymphoma (MZL). Most MZL arises in mucosa-associated lymphoid tissue (MALT), either in the stomach or in a range of other organs such as salivary glands, the tissues around the eye or the thyroid. Many stomach MALT lymphomas are caused by infection with Helicobacter Pylori. This infection can also be associated with non-gastric MALT lymphomas, but the association has never been prospectively studied. Chlamydia Psittaci infection can cause MALT lymphoma in the orbit. The management of localised MZL outside the stomach is controversial and there have been no large prospective studies of any of the commonly-used treatments (radiotherapy, chemotherapy, surgery). No prospective studies have looked at the role of infection with Helicobacter pylori or the role of autoantibodies in these diseases. Radiotherapy is the best-characterised therapy in the literature and appears to have a high cure rate with low toxicity. The disease seems exquisitely radiosensitive. Management of localised MZL in Australia can be ad hoc and we have often seen patients who have undergone unnecessary mutilating surgery or ineffective chemotherapy. It has been reported that localised non-gastric MZL (stage I and II) can be cured with radiotherapy in a high percentage of patients (usually >70%) in retrospective studies from large centres such as Princess Margaret Hospital in Toronto. Workers from that centre will participate in this study. This study will: Prospectively report efficacy and toxicity for radiotherapy in MZL for the first time Definitively document Helicobacter Pylori status in all cases and Chlamydia status in orbital cases Provide a gold standard against which to compare new therapies This study won the award for the most highly supported study in its year at the TROG annual scientific meeting.Read moreRead less