Role For Sphingosine Kinase-1 In Endothelial Progenitor Cell Survival And Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$294,205.00
Summary
Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand th ....Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand the process whereby mature endothelial cells are formed and how replacement of damaged endothelial cells is normally achieved. Stem cell therapy is considered the new frontier for the treatment of many diseases. Understanding how endothelial progenitor cells differentiate to mature endothelial cells and the signals which operate inside the cell may allow therapeutic manipulation of key target moecules in order to limit or control inflammation, tumourigenesis, rheumatoid arthritis and diabetic retinopathy. Our results suggest that one target maybe the enzyme sphingosine kinase.Read moreRead less
Vaccines aim to protect against future infections by inducing memory in the immune system so that the host can react quickly to the next challenge. Defence against viral infections and some cancers depends in part on activating CD8+ T cells, a class of white blood cell that can recognise and kill infected or malignant cells. The ideal vaccines against these challenges would therefore generate high numbers of long-lived CD8+ T cells that are programmed to make the right response if the infection ....Vaccines aim to protect against future infections by inducing memory in the immune system so that the host can react quickly to the next challenge. Defence against viral infections and some cancers depends in part on activating CD8+ T cells, a class of white blood cell that can recognise and kill infected or malignant cells. The ideal vaccines against these challenges would therefore generate high numbers of long-lived CD8+ T cells that are programmed to make the right response if the infection or tumour re-emerges. Little is known about the programming of memory CD8+ T cells. We have recently found that some of these cells have the potential to be reprogrammed to display different functions by exposure to new stimuli. This opens up the possibility that ineffective responses could be improved by using vaccination to control the production of these flexible or multipotential memory cells or to reprogram them once they are formed. Alternatively, effective responses might be subverted by pathogens to the detriment of the host. The goal of this project is to learn how the first exposure to an immune challenge influences the development of these multipotential memory CD8+ cells. Understanding the signals and processes that generate multipotential memory cells will be the first step towards developing ways to manipulate them to improve immune defence.Read moreRead less