CHARACTERISATION AND ANTIBODY-MEDIATED TARGETING OF A NOVEL SPECIFIC MARKER FOR T CELL ALL/LYMPHOBLASTIC LYMPHOMA
Funder
National Health and Medical Research Council
Funding Amount
$586,146.00
Summary
Improvements in treatment have seen some types of leukaemia (a cancer of white blood cells) being curable in up to 90% of patients with the disease; however, other types of leukaemia do not respond to these drugs and new approaches are needed. We have discovered that some leukaemia cells express a unique protein not made by any other cell type. This project will analyse how this aberrant protein is made and how this process contributes to the development of leukaemia. Also, since this protein is ....Improvements in treatment have seen some types of leukaemia (a cancer of white blood cells) being curable in up to 90% of patients with the disease; however, other types of leukaemia do not respond to these drugs and new approaches are needed. We have discovered that some leukaemia cells express a unique protein not made by any other cell type. This project will analyse how this aberrant protein is made and how this process contributes to the development of leukaemia. Also, since this protein is unique to the leukaemia cells, it offers the opportunity to develop magic bullets able to target specifically to the leukaemia cells and to kill them. This project aims to make one such drug and to conduct preliminary testing.Read moreRead less
Immunopathogenesis Of Organ-specific Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$284,638.00
Summary
The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. Our studies will employ state-of-the art technologies to further our knowledge of this class of diseases and to uncover the normal mechanisms that allow the immune system to differentiate foreign and self components.
Proteolytic And Non-proteolytic Roles For PSA And Related Kallikrein Serine Proteases In Prostate Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$480,128.00
Summary
Prostate cancer is the most frequently occurring cancer in men in Western countries. Prostate cancer metastasis to bone and other organs is the painful end stage of this disease. The level of prostate specific antigen (PSA) in blood is often used as a marker of prostate cancer. PSA is one of 15 related enzymes in the kallikrein family of enzymes, which may be involved in breakdown of the tissue that surrounds cells in the prostate. As prostate cancer metastasis first requires spread from the pri ....Prostate cancer is the most frequently occurring cancer in men in Western countries. Prostate cancer metastasis to bone and other organs is the painful end stage of this disease. The level of prostate specific antigen (PSA) in blood is often used as a marker of prostate cancer. PSA is one of 15 related enzymes in the kallikrein family of enzymes, which may be involved in breakdown of the tissue that surrounds cells in the prostate. As prostate cancer metastasis first requires spread from the primary tumour and out of the prostate, it is possible that high production of these kallikrein enzymes by prosttae cancer cells may increase the ability of these cells to metastasise. In previous work, we have studied prostate cancer cells that we have engineered to make the kallikreins, PSA and kallikrein 4. Those cells that make PSA or kallikrein 4 are more elongated in shape and are better able to move across a porous barrier. Another important change is that these cells stop producing a protein that is usually found on the surface of these cells and is important for helping cells to stay attached to each other. When this protein is lost, these tumour cells no longer stay attached to each other and are more likely to move out of the prostate and spread into other parts of the body. The changes we observed in the cells that produce PSA and kallikrein 4 are typical of these more aggressive cancer cells. In this project, we will look at how PSA and kallikrein 4 cause the cells to undergo these changes. The majority of prostate cancer deaths arise from cancer that has spread from the primary tumour and out of the prostate capsule. This project aims to further understand the causes of prostate cancer spread and metastasis. This is a vital research priority if we are to address the mortality associated with prostate cancer metastasis and may lead to new treatment approaches for advanced metastic prostate cancer.Read moreRead less
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
Understanding The Complexity Of Antigen Presentation
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
I have developed and established the use of mass spectrometry to identify and quantitate ligands of antigen presenting molecules to understand the breadth of immune responses in a variety of human disease states including autoimmunity, cancer, infection and allergy. By embedding the technology in disease focussed research programs I will define the molecular bases of these diseases and the important immunological targets that will provide new avenues for therapeutic development and vaccines.
Investigation Of Small Molecule Interactions With The Human Leukocyte Antigen And Their Role In Non-infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The Human Leukocyte Antigens (HLA) play a key role in the immune system helping the body differentiate healthy from diseased cells. Numerous autoimmune diseases and adverse drug reactions are associated with specific HLA variants. This study seeks to unlock the mechanisms behind these diseases, investigating how small molecules including drugs interact with the HLA to make healthy body cells seem foreign. This research has the potential to inform strategies for disease avoidance and management.