Centre for Transplant and Renal Research

The focus of our research group is to improve the lives of people with end-organ failure through transplantation and to reduce the number of people requiring dialysis by preventing the progression of chronic renal disease.

We aim to do this by focusing on research outcomes that can be translated into clinical therapy and new treatments for patients.

On this page you will find information on:

• Pancreatic Islet Cell Transplantation
• Pancreatic Islet Cell Transplantation
• Transplantation Immunity and Tolerance
• Chronic Allograft Nephropathy Research
• Research Groups

Clinical Associate Professor Philip O'Connell is the Director of the Centre for Transplant and Renal Research.

Pancreatic Islet Cell Transplantation

Following our units pioneering clinical trial of pancreatic islet transplantation we have been chosen to lead an Australian wide consortium with the aim of developing pancreatic islet transplantation as a mainstream therapy for patients with difficult to control diabetes. The original trial involved six patients with severe metabolic complications from their diabetes. Five of the six had marked improved metabolic outcomes after successful pancreatic islet transplantation and three patients no longer required insulin injections for substantial periods of time. This trial identified progressive loss of islet graft function and complications from the anti-rejection drugs as the major impediments to it more widespread application. The new study, which has been funded by the Federal Government and the JDRF aims to identify factors that cause graft damage and to develop a safer immunosuppressive regimen.

Pancreatic Islet Cell Transplantation

Currently pancreatic islet cell transplantation is the only known cure for Type I diabetes. If this therapy is to be more effective a sources of insulin producing cells other than organ donors needs to be found. In collaboration with researchers in Melbourne and Adelaide we are investigating the use of pig pancreatic islet cells for future transplantation in human patients. Our current research is focused on understanding the mechanisms of early islet cell loss. This appears to be due to a combination of clotting and early cellular rejection. Our data would suggest that producing pigs whose islet cells express several human proteins that regulate clotting and rejection may be sufficient to allow this tissue to be used safely in patients. This information has been used to develop a new line of pigs that have been genetically modified so that they may be better suited to clinical transplantation. Australia is the world leader in pig transgenesis and this ambitious collaborative project between four research institutes is making substantial progress in the development of pig islet cell xenotransplantation.

 

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Transplantation Immunity and Tolerance

The aim of this group is to better understand the mechanisms of rejection of pancreatic islet xenografts and to develop novel strategies for suppressing this immune response. The group has made several novel findings in understanding the role macrophages play in the rejection of pig islet grafts. In particular we have shown that macrophages have a surprisingly specific and sophisticated recognition response for identifying pig tissue. At present work in this area is focusing on understanding the molecular mechanisms responsible for this recognition. In particular we have focused on a group of macrophage receptors called toll receptors and have found that they have an important role in regulating macrophage recognition of pig tissue. The group is also investigating novel strategies to induce tolerance to transplanted islet tissue and to further reduce the requirement for long-term immunosuppression. In particular they are focusing on the role of a regulatory T cell called CD4CD25+ T cells. They have found that these cells are capable of inducing tolerance to islet allografts and have begun investigating their role in maintaining tolerance to pig islet cells.

 

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Chronic Allograft Nephropathy Research

The aim of this group is to increase our knowledge about the mechanisms for the long-term loss of renal transplant. Current treatment strategies are very good at preventing acute cellular rejection but over time renal transplants are still lost to a complex process known as Chronic Allograft Nephropathy. The group has been at the forefront of this research internationally and by studying protocol biopsies has identified several novel factors responsible for this chronic graft loss. The focus of the group is to understand the molecular mechanisms responsible for this loss using a genome wide analysis of biopsy specimens using genomics or gene chips. This had allowed us to identify early mechanisms of graft fibrosis and glomerulosclerosis. This has allowed us to understand better the early pathology that ultimately leads to chronic allograft nephropathy. Ultimately it will allow us to develop a diagnositic test that predicts those patients that will develop this condition and to design new treatments. In the last 6 months we have been successful in obtaining funding from the National Institutes of Health in the US to take part in a large multicentre study that will identify the genomics of Chronic Allograft Nephropathy.

Research Groups

The Centre has the following Research Groups:

Clinical Stream Director

Dr Jeremy Chapman

T +61 2 9845 6349
F +61 2 96339351
E Jeremy_Chapman@wsahs.nsw.gov.au