The Molecular Basis Of HLA-linked Drug Hypersensivity Reactions
Funder
National Health and Medical Research Council
Funding Amount
$683,040.00
Summary
Adverse drug reactions are one of the leading causes of death in hospitalised patients. We have discovered a new mechanism that links these reactions to recognition of drug induced changes in immunological self, resulting from interactions of drugs with immune receptors. This project probes the generality of this mechanism by examining the basis of life threatening reactions to drugs used to treat epilepsy (carbamazepine), gout (allopurinol), HIV (Nevirapine) and towards aspirin a commonly used ....Adverse drug reactions are one of the leading causes of death in hospitalised patients. We have discovered a new mechanism that links these reactions to recognition of drug induced changes in immunological self, resulting from interactions of drugs with immune receptors. This project probes the generality of this mechanism by examining the basis of life threatening reactions to drugs used to treat epilepsy (carbamazepine), gout (allopurinol), HIV (Nevirapine) and towards aspirin a commonly used pharmaceutical.Read moreRead less
Antigen Presentation During HLA B27 Associated Auotimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$715,365.00
Summary
Ankylosing spondylitis is a debilitating arthritic disease, susceptibility to which is conferred by genes of the immune system, particularly HLA-B27, and following gastrointestinal infection. Using mass spectrometry we will identify bacterial peptides bound to HLA-B27 on infected cells that may trigger an autoimmune response. Defining the self peptides that remain the targets of autoimmunity will unravel the molecular and cellular mechanisms if disease and identify peptides for immunotherapy.
The Molecular Basis Of HLA-linked Drug Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$827,536.00
Summary
Adverse drug reactions are one of the leading causes of death in hospitalised patients. We discovered a new mechanism that links these reactions to recognition of drug induced changes in immunological self, resulting from interactions of drugs with immune receptors. This project continues to probe the mechanisms of immune mediated drug reactions by examining the basis of life threatening reactions to drugs used to treat epilepsy, gout and commonly used drugs such as penicillin and aspirin.
Unraveling The Link Between HLA B27 And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$746,102.00
Summary
Ankylosing spondylitis and related diseases cause significant morbidity in up to 0.25% of the population. Current treatments have limited efficacy and often debilitating side effects. More targeted peptide antigen based therapies will have fewer side effects and would be of major clinical importance to this group of diseases. This project seeks to identify peptide antigens that could be used in targeted immunotherapy. We also seek to understand how some of the idiosyncratic properties of HLA B27
Failure Of Donor Antigen Presentation Promotes IL-17 Dependant Chronic GVHD
Funder
National Health and Medical Research Council
Funding Amount
$585,860.00
Summary
Bone marrow transplantation (BMT) is the most effective treatment for a number of haematological conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which d ....Bone marrow transplantation (BMT) is the most effective treatment for a number of haematological conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which drive GVHD.Read moreRead less
Analysis Of Human CD4+ T-cell Responses To Epitopes Formed By Peptide Fusion In The Pathogenesis Of Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,239,989.00
Summary
Type 1 diabetes is caused by immune-mediated destruction of the insulin-secreting beta cells. Recently we discovered new targets ‘seen’ by the immune system that may explain why the immune system causes type 1 diabetes. Here we will determine if responses to these targets cause type 1 diabetes. This is important because it tests a new idea and our results will have a major impact on efforts to develop new therapies for type 1 diabetes an other autoimmune diseases.
The Role Of Gut Resident Antigen Presenting Cells In Graft-versus-host Disease
Funder
National Health and Medical Research Council
Funding Amount
$409,909.00
Summary
Allogeneic stem cell transplantation (SCT) is curative therapy for most blood cancers, since donor immune cells can eliminate cancers which cannot be eradicated by chemotherapy. However these donor cells can also attack normal cells in a process known as graft-versus-host disease. This research aims to understand how immune responses are induced after SCT to promote cancer eradication, whilst inhibiting GVHD, thus curing more patients of cancer and maintaining a normal quality of life.
The Impact Of Therapy On T-cell Recognition Of Mutated Tumour Neo-antigens
Funder
National Health and Medical Research Council
Funding Amount
$1,126,685.00
Summary
Cancer is caused by mutations which should be 'seen' and destroyed by the patients immune cells, similar to how immune cells protect us against viruses. But they don't. This grant will study how current cancer treatments help the immune cells 'see' these mutations. We will undertake these studies in the important cancers lung cancer and mesothelioma.
A Novel Role For MHC Class II In Carbohydrate Presentation
Funder
National Health and Medical Research Council
Funding Amount
$703,030.00
Summary
Cells of the immune system swallow up foreign molecules and break them down to smaller fragments. T cells then identify the degraded antigen fragments and coordinate the immune response. In this project we will investigate how the T cells identify carbohydrates.
Role Of The CD8-Heparan Sulfate Interaction In CD8+ T Cell Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$649,135.00
Summary
The immune system can recognise a large array of foreign pathogens without reacting to self-components. For this to occur T cells, the main mediators of immunity, must be made to tolerate self-molecules as they develop in the thymus. We have identified a novel interaction between a molecule called CD8 on T cells and a complex carbohydrate called heparan-sulfate, which helps auto-reactive T cells to be eliminates in the thymus. The aim of this project is to further investigate this phenomenon.