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.
Tolerogenic Dendritic Cells In Common Marmoset Renal Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$162,756.00
Summary
ORGAN TRANSPLANT PATIENTS currently need life-long immune suppressing drugs to prevent rejection, often using 15 medications a day, costing Australia $52M in 2002. These drugs increase risks of infection and cancer. 90% of patients develop some form of cancer over 30 years. They also cause non-specific side effects including high blood pressure, diabetes and osteoporosis. The average lifespan of a kidney transplant is 8-15 years. Major causes of kidney transplant loss are rejection and drug toxi ....ORGAN TRANSPLANT PATIENTS currently need life-long immune suppressing drugs to prevent rejection, often using 15 medications a day, costing Australia $52M in 2002. These drugs increase risks of infection and cancer. 90% of patients develop some form of cancer over 30 years. They also cause non-specific side effects including high blood pressure, diabetes and osteoporosis. The average lifespan of a kidney transplant is 8-15 years. Major causes of kidney transplant loss are rejection and drug toxicity. TRANSPLANTS ARE REJECTED when a recipient's immune system sees the kidney as foreign. Immune suppressing drugs prevent rejection by stopping the reaction to foreign tissues, but this causes increased infection and cancer risk. IMMUNE TOLERANCE means the recipient's immune system sees a transplant not as foreign but as part of itself, no longer reacting to it. If tolerance could be achieved for transplants, patients wouldn't need to use immune suppressing drugs. Costs of immune suppression would be nil. Tolerance is the best long-term solution for patients needing transplants. Tolerance has been achieved in various ways in mice models. DENDRITIC CELLS can be used to induce tolerance as they can silence a recipient's immune system, preventing it from seeing transplant tissues as foreign. We have shown in mice that a single infusion of a certain type of dendritic cells caused prolonged transplant tolerance without needing immune suppression. This project aims to use dendritic cells to induce tolerance in a marmoset model - a required step before allowing this therapy to be done in humans. PRIMATES like MARMOSETS have close genetic identity to humans and are ideal transplant models as their immune systems react much more like humans than other animals. Marmosets are not an endangered species and are smaller, cheaper and easier to care for than other primates. Ultimately, experiments in other species would need repeating in primates before human trials could be done.Read moreRead less
TOLERANCE OR REJECTION – THE ROLE OF INNATE IMMUNITY IN DETERMINNG THE FATE OF A KIDNEY ALLOGRAFT
Funder
National Health and Medical Research Council
Funding Amount
$506,413.00
Summary
Transplantation is the optimal management for people with organ failure. Tolerance, to retain transplant function without immunosuppression, remains the key goal but is seldom achieved. We propose to block Toll-like receptor signalling to achieve kidney transplant tolerance in mice. If successful, we would translate this into clinical trials in human, seeking to achieve organ transplantation without the risks of cancer, infection and premature death that are currently faced by organ recipients.
Strategies To Achieve Kidney Transplant Tolerance In A Clinically-relevant Model
Funder
National Health and Medical Research Council
Funding Amount
$663,490.00
Summary
The acceptance of kidney transplants without immunosuppression (tolerance) would avoid the side effects of these powerful drugs and improve long-term graft survival. Donor brain death causes inflammation in transplanted kidneys which can block tolerance. In this project, we aim to determine whether expression of a naturally-occurring soluble anti-inflammatory molecule in the liver can prevent this inflammation, allowing tolerance to develop.
Serial NT-proBNP Monitoring For Predicting Major Cardiovascular Events In The Dialysis Population
Funder
National Health and Medical Research Council
Funding Amount
$288,548.00
Summary
Dialysis patients have a 50-100 fold increased risk of dying from heart disease caused by abnormal heart muscle structure and function. Current tests are unable to accurately identify patients at the highest risk. A test that accurately detects the early stages of heart injury is urgently needed. The aim of our research is to develop a monitoring guide using regular testing of a heart hormone (NT-proBNP) to identify high-risk dialysis patients early allowing treatment before a serious medical co ....Dialysis patients have a 50-100 fold increased risk of dying from heart disease caused by abnormal heart muscle structure and function. Current tests are unable to accurately identify patients at the highest risk. A test that accurately detects the early stages of heart injury is urgently needed. The aim of our research is to develop a monitoring guide using regular testing of a heart hormone (NT-proBNP) to identify high-risk dialysis patients early allowing treatment before a serious medical complication occurs.Read moreRead less
A Life Course Approach To Improving The Health And Well-being Of Young People With Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$193,360.00
Summary
Children with kidney disease suffers from profound ill-health and adopt a restrictive lifestyle, including dietary restriction, absences from school and other co-curricular activities. New knowledge and interventions are needed to address the pressing needs including of these children and their caregivers. This program of work will adopt a life-course approach to determine the protective and risk factors that affect the overall health and well-being of children with chronic kidney disease.
Identifying Donor And Recipient Gene Pathways In Renal Transplant Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,082,069.00
Summary
We have identified a 13 gene set that predicts renal transplant fibrosis and graft loss in patients. Interestingly some of these gene are donor as well as recipient related. In this project we aim to investigate these gene pathways in cell lines and animal models to better understand how the cause of renal fibrosis after transplantation.
20% of transplanted kidneys undergo rejection. This can permanently damage or destroy the transplant. Presently, rejection is identified when the kidney function deteriorates. This can occur late after rejection has started. To confirm the diagnosis of rejection, an invasive biopsy associated with discomfort and risks is required. This study will evaluate the use of a simpler blood test to monitor for rejection, allowing earlier and safer identification and treatment.