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.
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.
This project will investigate the factors that regulate the development and maintenance of a recently identified population of white blood cells called MAIT cells. MAIT cells are abundant in humans yet poorly understood. A better understanding of how these cells are regulated, and how they can be targeted in diseases, is necessary if we want to ultimately use these cells for immunotherapy.
MAIT cells are a recently discovered type of lymphocyte that plays a unique and important role in the immune system. However, these cells vary widely in number between healthy individuals, for reasons that are unclear. This project is designed to understand the factors that control the development of MAIT cells as a step toward regulating their numbers and activity.
Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.
Antigen-presenting cells control immune responses. Different types of these cells do different jobs and affect different diseases. We wish to control these processes by determining how the cells live and die. In particular we are interested in controlling the local immune responses during rejection of islet transplantation, which can cure type 1 diabetes.
I am a cellular immunologist with expertise in antigen processing-presentation, CTL determinant selection and immunodominance, T cell differentiation and, cancer immunotherapeutic trials and cancer vaccine development.