CD39 Protects Against Renal Ischaemic-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$441,584.00
Summary
In many medical settings, such as heart attacks, strokes, transplantation, heart surgery, shock and infection, the blood supply to an organ may be compromised resulting in damage. The cessation of blood flow depletes the organ of oxygen and generates a number of toxic changes. Re-establishing blood flow to the organ is essential to prevent further damage, however the reestablishment of blood flow itself can be harmful to the organ. The return of blood flow, oxygen and energy can actually promote ....In many medical settings, such as heart attacks, strokes, transplantation, heart surgery, shock and infection, the blood supply to an organ may be compromised resulting in damage. The cessation of blood flow depletes the organ of oxygen and generates a number of toxic changes. Re-establishing blood flow to the organ is essential to prevent further damage, however the reestablishment of blood flow itself can be harmful to the organ. The return of blood flow, oxygen and energy can actually promote more widespread injury - a process known as ischaemia-reperfusion injury (IRI). A greater understanding of IRI should aid in the development of drugs that minimise its impact. The overall aim of this work is to examine the role of a molecule - CD39 - in IRI. This molecule is ideally situated to minimise injury - it is located on cells that line blood vessels and, as such, is able to directly neutralise toxins released in response to this injury. We, therefore, believe that it will be protective in this setting. We have developed animals that express this molecule and have preliminary results to suggest that these animals are protected in experimental models of IRI as well as in several other models including heart transplantation surgery; processes that share many features with IRI. Moreover, mice deplete of this molecule are prone to more severe IRI. We aim to investigate this by using animals both lacking and expressing CD39. Blood flow to the kidneys will be interrupted for 30 minutes and kidney function assessed at 24 and 48 hours. We will then delve into the potential mechanisms underpinning IRI by determining whether the kidney itself or the blood cells afford protection, which has direct clinical implications.Read moreRead less
Combining Immune Monitoring And Immunotherapy To Tackle Cytomegalovirus Infections In Solid Organ Transplant Patients
Funder
National Health and Medical Research Council
Funding Amount
$801,416.00
Summary
Clinical management of infectious complications in kidney and heart/lung transplant patients remains significant challenge. Although prophylactic/pre-emptive treatment with antiviral drugs have shown dramatic improvements in the control of these infections, long-term treatment with these drugs is associated with significant toxicity, the appearance of drug-resistant virus isolates and significant health cost. In this proposal we will develop novel strategies to identify high risk patients and tr ....Clinical management of infectious complications in kidney and heart/lung transplant patients remains significant challenge. Although prophylactic/pre-emptive treatment with antiviral drugs have shown dramatic improvements in the control of these infections, long-term treatment with these drugs is associated with significant toxicity, the appearance of drug-resistant virus isolates and significant health cost. In this proposal we will develop novel strategies to identify high risk patients and treat these patients with killer T cells.Read moreRead less
Investigating The Function Of Natural Killer Cells During Immunological Responses Following Human Lung Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$71,766.00
Summary
The immune system is critical in controlling common viral infections in healthy individuals. When transplanting foreign solid organs into patients with end-stage lung disease the immune systemÍs activity is decreased via the immunosuppressive drugs to enable graft acceptance. In some patients the immune response can detect similarities between previously encountered viruses and the foreign organ, leading to life-threatening health problems through either rejection episodes and/or graft loss.