Improving Transplant Outcomes Through Translational Research
Funder
National Health and Medical Research Council
Funding Amount
$406,585.00
Summary
The aim of my research is to improve transplant outcomes by developing novel, clinically realistic, therapeutic options for patients with end-organ failure and for a specific cohort of patients with type 1 diabetes. The goal is to advance transplantation by developing a strong interactive research environment where initiatives are quickly interchanged between the laboratory and the clinic. These include novel trials in islet transplantation and use of genomics to improve transplant outcomes.
Building a death-defying islet beta cell Type I diabetes results when the cells that produce insulin (the islet beta cells) are killed by the immune system. The beta cell, like any other cell in the body, can be induced to die by activation of a process that leads to cell suicide. During this process, enzymes dismantle the structure of the cell and the remains are eaten by neighboring cells. In diabetes, the stimulus for beta cell suicide is provided by a number of agents most of which are made ....Building a death-defying islet beta cell Type I diabetes results when the cells that produce insulin (the islet beta cells) are killed by the immune system. The beta cell, like any other cell in the body, can be induced to die by activation of a process that leads to cell suicide. During this process, enzymes dismantle the structure of the cell and the remains are eaten by neighboring cells. In diabetes, the stimulus for beta cell suicide is provided by a number of agents most of which are made by the T cells of the immune system. Our aim is to interfere with this cell suicide process and engineer a beta cell that can resist T cell attack. Because genetically manipulated mice provide the flexibility we need to add and subtract genes from the beta cell we will use them as a model to build a death-defying beta cell. We will investigate three strategies. Firstly, cells will be engineered to express a molecule (CD30 ligand) which recognizes a protein on the surface of the attacking T cells and in so doing, sends a signal to the T cells to stop proliferating. Secondly, we will remove proteins (CD95, TNFRI) from the surface of the beta cell, that attacking T cells use to set in motion the cell suicide process. Thirdly, we will engineer beta cells that express inside themselves, cell death inhibitor proteins (Bcl-2, CrmA, p35) that can prevent the automatic process of cell suicide. It is our hope that studies with death-defying beta cells will find a new way to manipulate islet tissue for transplantation. In patients with diabetes, the beta cells have all been destroyed but the attacking T cells still remain. As a result, transplants of new beta cells are rapidly damaged. Beta cells that can resist ongoing immune attack may survive well enough to reverse the symptoms of diabetes. The success of this research could have an impact on a cure for diabetes.Read moreRead less
Improving Outcomes Of Transplantation By Targeting Retrieval, Care And Complications
Funder
National Health and Medical Research Council
Funding Amount
$70,750.00
Summary
Our aim is to find out what the problems related to organ transplantation are in order to suggest ways of intervening to help reduce these problems for patients and the health care system. We will work closely with the team at one of Australia's leading transplant centres at Westmead Hospital to try and find safe and economic ways to tackle issues of organ shortage, those that come up during the organ donation and in the wider care of patients improve the practice.
Role Of The Hypoxia-inducible Transcription Factor HIF-1a In Controlling Haematopoietic Stem Cell Fate
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
Haematopoietic stem cells (HSCs) reside in the bone marrow (BM) and make all immune and blood cells. We have found that, in the areas of the BM where HSC normally live, the level of oxygen is very low (hypoxia) and decreases even further when HSC are forced to move into the blood in order to be collected for transplantation. This project is to better understand how oxygenation of the BM controls HSC behaviour and properties, and to evaluate its impact on HSC transplantation.
Why Does Peripheral Airway Dysfunction Lead To Broncholitis Obliterans Syndrome In Lung Transplantation?
Funder
National Health and Medical Research Council
Funding Amount
$312,927.00
Summary
The uneven way that airways narrow (heterogeneity) is an important factor affecting the natural history, clinical expression and response to treatment in patients following lung transplantation. In the proposed study we plan to monitor the heterogeneity of the airways in patients immediately following lung transplantation and relate these changes to immunological markers of lung rejection.
Investigation Into The Role Of Regulatory B Cells In Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$400,385.00
Summary
Solid organ transplantation is the most effective therapy for treating organ failure and some cancer. However, a common complication that occurs is graft rejection. The current aim is to develop procedures that reduce the risk of graft rejection without the use of immunosuppressive drugs, which can be toxic and make recipients more susceptible to infection. We are investigating the ability of a cell that is part of the immune system to down-regulate over-reactive immune responses and therefore r ....Solid organ transplantation is the most effective therapy for treating organ failure and some cancer. However, a common complication that occurs is graft rejection. The current aim is to develop procedures that reduce the risk of graft rejection without the use of immunosuppressive drugs, which can be toxic and make recipients more susceptible to infection. We are investigating the ability of a cell that is part of the immune system to down-regulate over-reactive immune responses and therefore reduce rejection.Read moreRead less