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
Kidney transplantation is a life-saving treatment for most people with end-stage kidney disease. For some people, however, it causes more harm than good. We will clarify which individuals will benefit from transplantation by personalising information on predicting potential outcomes after transplantation. We will use this to develop a decision tool to help doctors and patients make these challenging and irreversible decisions. This will maximise the benefits from this precious resource.
A Phase 1 Clinical Trial Of A Human Chimeric Anti-Activated DC Antibody To Prevent AGVHD In High Risk Allo HSCT.
Funder
National Health and Medical Research Council
Funding Amount
$670,736.00
Summary
Bone Marrow transplants provide life saving therapy for leukaemias, lymphomas and other life threatening blood disorders. One of the major life threatening complications is acute graft versus host disease (AGVHD) in which the doner immune system damages the patient's skin, liver and gut, amongst other tissues. Dendritic cells initiate and direct immune responses. We have shown that dendritic cells are central to the initiation of AGVHD and have shown that a marker called CMRF-44 is expressed on ....Bone Marrow transplants provide life saving therapy for leukaemias, lymphomas and other life threatening blood disorders. One of the major life threatening complications is acute graft versus host disease (AGVHD) in which the doner immune system damages the patient's skin, liver and gut, amongst other tissues. Dendritic cells initiate and direct immune responses. We have shown that dendritic cells are central to the initiation of AGVHD and have shown that a marker called CMRF-44 is expressed on activated dendritic cells before AGVHD emerges. We have developed potential new therapeutic antibodies that target activated dendritic cells and shown that they are effective in preclinical studies. This project will further validate these antibodies, then test their safety and their ability to prevent AGVHD in patients. The trial will also test whether they have the expected additional beneficial effect of preserving protective anti-viral and anti leukaemic immune responses.Read moreRead less
In Vivo Real-time Tracking Of “color-coded” Supercharged Mesenchymal Stem Cells And T Cells In Allograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Growing specialized adult stem cells (MSC) in the presence of a unique immune signaling protein (IL-17) has generated a “supercharged” stem cell with superior abilities to dampen immune responses in cell and organ transplant patients. The use of these MSC in transplant patients may significantly reduce the dose of anti-rejection drugs required to prevent cell and organ rejection. By minimizing the dose of drugs, we aim to eliminate the risk of developing infections and cancer in these patients.
Production Of A Novel Humanised Anti Dendritic Cell Therapeutic Antibody For Graft Versus Host Disease
Funder
National Health and Medical Research Council
Funding Amount
$202,500.00
Summary
A transplant of bone marrow or other source of blood stem cells from a donor is often used to treat leukaemia patients whose disease has failed to respond to chemotherapy. The Mater Medical Research Institute has developed a world first dendritic cell depleting therapeutic antibody which may open a new strategy for the control of acute graft versus host disease, which is a very common and often fatal complication of bone marrow transplantation. The new antibody treatment is also likely to be use ....A transplant of bone marrow or other source of blood stem cells from a donor is often used to treat leukaemia patients whose disease has failed to respond to chemotherapy. The Mater Medical Research Institute has developed a world first dendritic cell depleting therapeutic antibody which may open a new strategy for the control of acute graft versus host disease, which is a very common and often fatal complication of bone marrow transplantation. The new antibody treatment is also likely to be useful for the prevention of rejection in solid organ transplantation. If successful, it will selectively control graft versus host disease, without compromising the essential anti-viral immunity and desired anti-leukemia activity of the graft.Read moreRead less
Mechanisms Of Immune Modulation By Human Cytomegalovirus During The Latent Phase Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$165,500.00
Summary
Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. CMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Bone marrow and solid organ transplant recipients are particularly at risk of developing serious CMV disease. CMV has the remarkable ability to hide in the body in a dormant or latent form for the life of the host. However, when conditions are right the virus can awaken (ie reactivate) from its ....Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. CMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Bone marrow and solid organ transplant recipients are particularly at risk of developing serious CMV disease. CMV has the remarkable ability to hide in the body in a dormant or latent form for the life of the host. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that reactivation from latency is of most medical significance, yet the latent phase of infection remains very poorly understood. We recently reported that during latent infection CMV interfered with the expression of a protein which plays a crucial role in our immune system. This protein is called MHC class II and its proper function is essential for our immune system to fight infections. Thus, we postulated that the ability of CMV to successfully hide in a cell in a latent state is at least partially due to its ability to interfere with the cells ability to properly make MHC class II proteins. This project aims to futher define and characterise the functions of latent CMV that enable it to interfere with our immune system. Firstly, we aim to continue with our studies to determine the mechanism by which latent CMV interferes with MHC class II expression. Secondly, we will seek to determine whether latent CMV interferes with any other important components of our immune system. Thirdly, we will seek to identify the precise viral gene that causes the interference with MHC class II expression. Determining the mechanism of immune system regulation and the viral gene(s) responsible for this interference may lead to the design of gene therapies to lessen the clinical impact of CMV disease in transplant recipients.Read moreRead less
Human Cytomegalovirus Gene Expression And Functions During Latent Infection And Reactivation
Funder
National Health and Medical Research Council
Funding Amount
$789,473.00
Summary
Human cytomegalovirus has the ability to hide in the body in a latent form for the life of the host. However, the virus can awaken (reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed people such as transplant patients that reactivation from latency causes significant morbitity and mortality, yet the latent infection remains very poorly understood. This project will identify and define the functions of viral genes that facilitate latency.
Analysis Of Viral And Cellular Gene Expression During Human Cytomegalovirus Latent Infection Of Hematopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$407,545.00
Summary
Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body a ....Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. This project has three major components. Firstly, we aim to continue studies which are defining what viral genes are active (ie expressed) during latent infection. Identification of these genes and determination of how they function may have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during latency and reactivation. The study of viral and cellular gene expression during latency may contribute to the development of drugs which interfere with the viruses ability to become latent or reactivate. Thirdly, we have preliminary results which suggest that latent HCMV may actively avoid detection by the immune system. In this project we also aim to determine the mechanism by which the virus interferes with the expression of molecules which are an essential component of our immune system.Read 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.
Viral And Host Cell Gene Expression During The Establishment And Maintenance Phases Of Human Cytomegalovirus Latency
Funder
National Health and Medical Research Council
Funding Amount
$149,250.00
Summary
Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and ....Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. The overall aim of these studies is to provide a much better understanding of how CMV latency is established and maintained, with the ultimate goal of making advances for the design of anti-viral therapies to disrupt these processes. This project has three major components: Firstly, we aim to identify and characterise viral gene expression during the establishment of latency and these findings will have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during the establishment and maintenance phases of latency. Thirdly, we will apply microarray technologies to determine how human cell genes are altered in response to the expression of individual viral genes that are active during the latent phase of infection.Read moreRead less