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Inflammatory diseases, such as autoimmune diseases, result from an overactive immune system. A new therapy that is currently under trial is the use of special blood cells, called Treg cells, whose function is to suppress unwanted immune responses. This application evaluates the efficacy and safety of such treatments.
Vaccinating Against Helicobacter Pylori-induced Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,088,714.00
Summary
Stomach cancer is the 3rd leading cause of cancer-related deaths. Most stomach cancers result from inflammation due to Helicobacter pylori infection. Most infections are treatable with antibiotics but this does not protect against cancers that develop before infection is diagnosed. Normal vaccine approaches aimed at this infection have been unsuccessful. We have identified a new approach for protecting against stomach cancer by preventing inflammation; this project aims to develop this vaccine.
Potassium Channel Regulation Of Bacterial-driven Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$576,000.00
Summary
Helicobacter pylori infections cause a chronic inflammation which in some people results in stomach cancer or ulcers. We have used a mouse with natural resistance to H. pylori gastritis to identify a completely novel regulator of the pathology induced by this infection. In this project, we will examine the mechanism by which this regulator protects against disease in mice, and examine its significance in the susceptibility of people to gastric cancer.
Novel Regulation Of Inflammasomes By Cytokine Signalling Pathways In Gastric Disease
Funder
National Health and Medical Research Council
Funding Amount
$674,772.00
Summary
Stomach inflammation (gastritis) is strongly associated with Helicobacter pylori bacterial infection, and can also progress to gastric cancer. However, it remains largely unknown how Helicobacter triggers these gastric diseases in people. Using a mouse model which develops gastric inflammation and tumours, our aim is to determine the role of protein complexes in the stomach called inflammasomes in triggering chronic inflammatory responses to Helicobacter that lead to gastric disease.
The Influence Of NF-KB In The Development Of Autoimmunity And Cancer In Fas/FasL Mutant Mice
Funder
National Health and Medical Research Council
Funding Amount
$596,925.00
Summary
Apoptotic cell death is an essential process in the human body, it removes useless and dangerous cells, preventing autoimmune disease and cancer. Apoptosis is activated when the surface receptor Fas is stimulated by its ligand, FasL, but defective signalling causes disease associated with deregulated NF-?B activation. We will investigate how faulty FasL-induced apoptosis cooperates with deregulated NF-kB activation or defective Aire (immunological tolerance orchestrator) results in autoimmunity.
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 Helminth-derived Peptide Is A Novel Prophylactic And Therapeutic Treatment For Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$658,778.00
Summary
Parasitic worms (helminths) secrete molecules that possess a remarkable ability to skew the mammalian immune system towards anti-inflammatory responses. We have expoited a novel peptide secreted by helminths, which offers tremendous potential for the development of novel prophylactic and therapeutic treatments for a range of immune-mediated conditions. The overarching aim of this project is to further elucidate the mechanism of action and to determine the peptide’s clinical application.
Molecular Signatures Of Public Clonotypes In Human Systemic Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$540,633.00
Summary
New platform technology has been developed to study autoantibody clones in lupus and Sjogren's syndrome. This approach has furthered our understanding of these disorders by the discovery of unique sets of clones that are common to all patients. The unique "molecular signatures" of these clones can be translated to a next-generation diagnostic that detects them in patients at extremely low levels missed by conventional tests.
The Axis Of Bcl-2, Plasmacytoid DCs And Lupus As A Basis For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$712,172.00
Summary
Systemic lupus erythematosus (SLE) affects 1 in 1000 Australians, mostly women. Here the immune system goes awry and makes antibodies against the body’s own components including the body’s DNA. This leads to damage to many parts of the body including kidneys, joints, brain and heart. It is incurable. A particular immune cell controls the development of this disease and we have found this cell is selectively killed by an inexpensive drug, which we hope will be a better way of treating SLE.
Hookworm Therapy In Coeliac Disease (CeD), Phase 1b
Funder
National Health and Medical Research Council
Funding Amount
$865,002.00
Summary
Parasitic worms have an amazing ability to manipulate the immune system, and our research group recently discovered how they may hold the key for treating inflammatory diseases such as Coeliac Disease. The aim of my research is to further develop this novel therapy in a clinical trial and study the mechanism of how worms control the immune response, including identifying the molecules that the worm produces that could be produced as a pill-based medication for treating coeliac disease.