Developing Clinical Islet Transplantation For Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$387,337.00
Summary
This fellowship will provide me the opportunity to advance islet transplantation as a curative treatment for people with type 1 diabetes. The ultimate goal is to use cell-based therapy to achieve insulin independence for all people with type 1 diabetes. It aims to do this by developing a collaborative network between scientists and clinicians to advance human islet transplantation as a treatment for type 1 diabetes and to develop genetically engineered pig cells as a novel source of insulin prod ....This fellowship will provide me the opportunity to advance islet transplantation as a curative treatment for people with type 1 diabetes. The ultimate goal is to use cell-based therapy to achieve insulin independence for all people with type 1 diabetes. It aims to do this by developing a collaborative network between scientists and clinicians to advance human islet transplantation as a treatment for type 1 diabetes and to develop genetically engineered pig cells as a novel source of insulin producing cellsRead moreRead less
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.
Beta Cell Mass In Type 1 Diabetes Mellitus And Islet Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$3,070,136.00
Summary
This research program will examine the cellular and molecular mechanisms underlying the loss of Beta cell mass and function: During the pathogenesis of Type 1 Diabetes Mellitus (T1D); and Following islet transplantation. Though these processes have traditionally been considered to be purely immune-mediated, it is now clear that the response of the beta cell is critical to the final outcome of the auto-immune process and response to therapeutic interventions. Thus the complex interactions between ....This research program will examine the cellular and molecular mechanisms underlying the loss of Beta cell mass and function: During the pathogenesis of Type 1 Diabetes Mellitus (T1D); and Following islet transplantation. Though these processes have traditionally been considered to be purely immune-mediated, it is now clear that the response of the beta cell is critical to the final outcome of the auto-immune process and response to therapeutic interventions. Thus the complex interactions between the cellular and soluble constituents of the immune system, plus the effects of a deregulated metabolic milieu, are integrated at the beta cell. This in turn activates a series of complex transcriptional programs in the beta cell that together determine the beta cells ultimate functional status and survival. We will use knowledge gained from studying these processes to drive the development of novel therapeutic targets and strategies to improve the success of immune-based and transplantation-based therapies.Read moreRead less
The Regulation Of Monocyte Derived Dendritic Cells (moDCs) During Allograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$110,218.00
Summary
Islet transplantation can cure type 1 diabetes, but the required drugs for immunosuppressing graft rejection have side effects. Therefore understanding how immune rejection occurs so that we can suppress in a more discreet selective way is our goal. A type of cell that is prominent during graft rejection is the monocyte derived dendritic cell. We propose that this cell is critical for orchestrating immune responses during rejection. Therefore we wish to determine how such cells are controlled.
The Role And Function Of Macrophages In Cellular Xenograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$323,250.00
Summary
The long term objective of this project is to develop pig insulin secreting tissue as a treatment for type 1 diabetes. At present the main barrier to this is rejection. In paricular a type of white blood cell called macophages has an important role in causing the rejection seen in xenotransplantation (the transplantation of pig tissue into humans). Our reseach group has made novel observations which show that the way macrophages respond to a xenotransplant is different to the way it behaves to t ....The long term objective of this project is to develop pig insulin secreting tissue as a treatment for type 1 diabetes. At present the main barrier to this is rejection. In paricular a type of white blood cell called macophages has an important role in causing the rejection seen in xenotransplantation (the transplantation of pig tissue into humans). Our reseach group has made novel observations which show that the way macrophages respond to a xenotransplant is different to the way it behaves to the transplant of an organ from the same species. In the rejection of pig insulin secreting tissue, macrophages are able to respond in the absence of ongoing signals from T cells. This project aims to identify the receptors on macrophages that are responsible for this response. In particular those receptors that are important for facilitating the migration of macrophages to the transplant site and the receptors that allow macrophages to distinguish self from non-self will be analysed. Hopefully these receptors will be used as targets for new therapeutic agents that could be used to prevent the strong rejection response that occurs when pig insulin secreting tissue is transplanted into humans.Read moreRead less
Functional Suicide Of Selected Dendritic Cells By Cytochrome C: An In Vivo Model Lacking Cross-presentation
Funder
National Health and Medical Research Council
Funding Amount
$597,476.00
Summary
Certain white blood cells (dendritic cells) activate the immune system, especially its T cells. Infection of such cells elicits killer T cell responses. However not all infections infect dendritic cells. In such cases, the infectious material is eaten by dendritic cells and moved to certain areas within the cell. This process is called cross-presentation and how important it is during various diseases remains moot. We now have a model of testing this by eliminating these cross-presenting cells.
Elucidating The Mechanism Of IL-2 Cytokine/antibody Mediated Transplantation Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Organ transplantation is a life-saving treatment for end-stage organ failure. However, patients must take immunosuppressive drugs to prevent rejection, a lifetime of which increases the risk of infection and cancer. An alternative to drugs is to manipulate the immune system from within. We discovered a way to boost the immune ‘regulators’ so that they stifle the graft-destroying response. We are optimising this approach with the aim of transplanting organs without long-term immunosuppression.
The current treatment for diabetes involves diet, drugs and insulin treatment. While these are satisfactory for some adult onset diabetes, it is clear that in juvenile diabetes, the disease can progress in the presence of careful insulin dosage. It is apparent that the whole islet as a functional unit is likely to give the best control of diabetes, as when patients are transplanted with whole or segments of pancreas from human donors, as not only is there an improvement in their diabetic status, ....The current treatment for diabetes involves diet, drugs and insulin treatment. While these are satisfactory for some adult onset diabetes, it is clear that in juvenile diabetes, the disease can progress in the presence of careful insulin dosage. It is apparent that the whole islet as a functional unit is likely to give the best control of diabetes, as when patients are transplanted with whole or segments of pancreas from human donors, as not only is there an improvement in their diabetic status, the vessel lesions improve. Transplantation therefore offers a new therapy to diabetic patients for reversal of their disease and improvement in the serious side affects found in the eye, kidney and blood vessels. However, transplantation introduces a problem in that there is simply not sufficient human islets available for organ or islet transplantation, and in this light, animals are being examined as a possible source of islets. This is called xenografting or xenotransplantation. Of all the animal species, the pig is the most suitable donor for a variety of reasons, for example similar control of blood sugar to humans. The ultimate aims of the study are to examine possible genetic modifications that would allow the production of transgenic pig islets for transplantation to humans for the treatment of diabetes. The focus of the proposed studies is to elucidate the optimal combinations using mouse models. Importantly this study will establish the proof of principle and provide information on the genes that will be useful to finally genetically modify pigs for clinical use.Read moreRead less
Mechanisms Of Islet Graft Rejection And Acceptance
Funder
National Health and Medical Research Council
Funding Amount
$602,501.00
Summary
Islet grafts offer diabetic patients the promise of a return to insulin-independence. In this project we will study how natural regulatory T cells suppress islet graft rejection in a mouse model. We will determine where regulatory T cells interact with graft-rejecting T cells, and define the mechanisms used to mediate their suppressive effects. Our findings will aid in developing new ways to induce long-term acceptance of islet grafts without immunosuppressive drugs.