The goal of our work is to improve outcomes for patients who are blind or seriously visually impaired as a result of corneal disease. Such patients can regain vision through a corneal transplant, but many such transplants fail. A corneal graft may fail because of an unwanted immune response, because blood vessels grow into the graft, or because some corneal cells die. We plan to transfer genes to the donor cornea in the laboratory, prior to corneal transplantation, to avoid such failure.
Antibody-mediated Dendritic Cell Depletion To Attenuate GVHD
Funder
National Health and Medical Research Council
Funding Amount
$434,510.00
Summary
Not all patients with leukemia will be cured by chemotherapy. Stem cell transplantation improves their chances of survival. Stem cell transplantation requires intensive chemotherapy and radiotherapy to eradicate the underlying disease and infusion of healthy stem cells to provide an anti-leukemic effect and normal blood cells. Recovery from transplantation is not straightforward. Recovery can be hampered by the immunological reaction of the donor cells against the patient (Graft versus Host Dise ....Not all patients with leukemia will be cured by chemotherapy. Stem cell transplantation improves their chances of survival. Stem cell transplantation requires intensive chemotherapy and radiotherapy to eradicate the underlying disease and infusion of healthy stem cells to provide an anti-leukemic effect and normal blood cells. Recovery from transplantation is not straightforward. Recovery can be hampered by the immunological reaction of the donor cells against the patient (Graft versus Host Disease [GVHD]), despite immunosuppression. GVHD produces serious damage to the internal organs and lining of the mouth and gut. Recovery can also be circumvented by leukemic relapse. GVHD is associated with an increased risk of death and dying after transplantation. To date therapy for GVHD has relied on eliminating the T cells that cause the disease. However for T cells to cause damage they must first be primed with antigen presented on activated dendritic cells. The intensive conditioning therapy required to eradicate the underlying disease before transplantation also activates dendritic cells. Our project seeks to investigate the effects of lethal and non-lethal conditioning on dendritic cells with the aim of validating the use of antibodies designed to deplete activated dendritic cells as therapy for graft versus host disease.Read moreRead less
Exertional Dyspnoea With Increased Filling Pressure - Mechanisms And Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$387,793.00
Summary
Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and theref ....Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and therefore, outcome) than with late stage disease. Current treatment strategies are expensive and because they are directed at end-organ damage (heart failure, heart attacks etc), rather ineffective. This multispecialty, multidisciplinary group will undertake a series of unique studies aimed at identifying early cardiovascular disease. The strategy will involve detection of abnormal filling behaviour at stress echocardiography, with randomization into longterm and short-term trials to examine various therapeutic strategies. Sensitive new cardiovascular imaging techniques will be used to detect preclinical abnormalities in the structure and function of the heart and vasculature, facilitating a mechanistic understanding of the process of increasing filling pressure with exercise.Read moreRead less
Antibiotic Loading Of Bone Allografts For The Prevention Of Peri-operative Infection
Funder
National Health and Medical Research Council
Funding Amount
$300,847.00
Summary
Bone is the second most often transplanted tissue after blood, with thousands of grafts done every year in Australia. Allograft bone (taken from another person) is used to replace bone removed due to cancer, but is prone to infection. Infected grafts must be removed, and can lead to amputation. We are developing a process to put antibiotics into allograft bone, to prevent infections from taking hold. Reducing infections can increase the success of limb salvage surgery for cancer patients.
The Role Of Dendritic Cells In Graft-versus-host Disease After Allogeneic Stem Cell Transplantation.
Funder
National Health and Medical Research Council
Funding Amount
$317,633.00
Summary
Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this proced ....Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this procedure. Research to date by Dr Hill and colleages has provided substantial detail on how and why this process occurs. This information has led to a number of advances in the field which are already improving patient survival after BMT. This includes a new type of bone marrow transplantation that uses a naturally ocurring growth factor (called a cytokine) to allow the collection of immature bone marrow cells from the blood of transplant donors. The transplantation of these cells rather than bone marrow appears to reduce the chance of dying during BMT and also improves the cure rates from the underlying leukemia. In addition, Dr Hill has developed a novel method for preventing GVHD using different types of naturally ocurring growth factors called cytokine shields that help protect patient tissue from attack by the immune system. It has recently become clear that the immune system is directed by a subtype of white cells called dendritic cells and Professor Hart at the Mater Medical Research Institute has been a pioneer in this field. As initiators of the immune system it is likely that dendritic cells play a pivotal role in GVHD and Dr Hill and Prof Hart at the Mater Medical Research Institute will study DC within the context of Dr Hills newly developed therapies with the aim of further understanding the processes of GVHD. This work will allow manipulation of these cells during BMT in order to improve patient survival.Read moreRead less
Allogeneic stem cell transplantation (SCT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. The ability to cure leukemia by this procedure relates to a process known as Graft-versus-Leukaemia effects (GVL) which ocurrs when the newly transplanted stem cells (which includes the immune system) recognises the leukemia as foreign and mounts an immune attack against it. These studies will focus on the effect of a cellular pathway invi ....Allogeneic stem cell transplantation (SCT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. The ability to cure leukemia by this procedure relates to a process known as Graft-versus-Leukaemia effects (GVL) which ocurrs when the newly transplanted stem cells (which includes the immune system) recognises the leukemia as foreign and mounts an immune attack against it. These studies will focus on the effect of a cellular pathway invilving NKT cells that preliminary data suggests is critical to the development of GVL. Methods to augment this activation pathway will be studied in preclinical models that may then be studied in clinical trials with the aim of improving the outcome of patients transplanted for leukemias.Read moreRead less
The Effect Of CPAP On Erectile And Endothelial Dysfunction In Impotent Men With Obstructive Sleep Apnea
Funder
National Health and Medical Research Council
Funding Amount
$609,559.00
Summary
Erectile dysfunction is common in men with obstructive sleep apnea, due to vascular damage, which leads to heart attack. CPAP is the preferred treatment for patients with OSA because of its well-proven ability to decrease sleepiness and improve blood pressure control. This study will establish if CPAP can also improve erectile and vascular endothelial dysfunction. These results will shed light on the mechanisms that underpin the relationship between OSA and Erectile Dysfunction.