Identification Of The Molecular Genetic Basis Of The Hepatic Veno-occlusive Disease With Immunodeficiency Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
One of the most serious complications of bone marrow transplantation is veno-occlusive disease (VOD), also termed sinusoidal obstruction syndrome (SOS). This condition occurs in 10% of transplanted patients and is characterised by abnormalities of liver function, enlargement of the liver, clotting abnormalities, fluid retention and finally failure of multiple organs and death in 30-50% of cases. The cause of VOD is unknown, and its occurrence cannot be predicted in individual patients. Eight fam ....One of the most serious complications of bone marrow transplantation is veno-occlusive disease (VOD), also termed sinusoidal obstruction syndrome (SOS). This condition occurs in 10% of transplanted patients and is characterised by abnormalities of liver function, enlargement of the liver, clotting abnormalities, fluid retention and finally failure of multiple organs and death in 30-50% of cases. The cause of VOD is unknown, and its occurrence cannot be predicted in individual patients. Eight families have been described in whom a number of individuals have succumbed to a condition which is clinically and histologically indistinguishable from VOD. Affected individuals also have a form of immunodeficiency (hence termed VODI), and the abnormalities are inherited in an autosomal recessive pattern. All eight are of Lebanese origin, suggesting that a single genetic ancestral mutation was responsible for the disorder in all families, who are distantly related. We have access to genetic material from three of these families, and are on the way to identifying the causative genetic abnormality. We hypothesise that understanding this abnormality will lead to an understanding of VOD which occurs after bone marrow transplantation. We have used 800 polymorphic genetic markers scattered throughout the genome to identify the location of the genetic abnormality, and have localised the defect to a region of chromosome 2 which contains approximately 37 known and predicted genes. We now aim to determine which of the gene(s) in the candidate region is responsible for VODI, and plan to examine DNA from individuals who have had VOD after transplantation to determine if they have a related abnormality. Finding the VODI gene will benefit these families through the availability of carrier detection and may also lead to an understanding of the veno-occlusive disease that occurs after bone marrow transplantation.Read moreRead less
Targeting Arginase In Peripheral Arterial Occlusive Disease
Funder
National Health and Medical Research Council
Funding Amount
$243,945.00
Summary
Peripheral artery occlusive disease causes narrowing of large peripheral blood vessels which can result in severe pain, gangrene and stroke. Its prevalence is steadily increasing in western countries. This proposal aims to characterize the role of an enzyme (arginase) in PAOD and determine whether it may be a new drug target for treatment of this disease.
Angiopoietin-2, Aortic Inflammation And Cardiovascular Events
Funder
National Health and Medical Research Council
Funding Amount
$332,161.00
Summary
Based on detailed preliminary data, we plan to investigate the importance of a novel protein (the cytokine angiopoietin-2) in cardiovascular disease. The results of this study will clarify the role of this cytokine in vascular pathology and may provide an important target for novel therapy and-or diagnostic markers for cardiovascular disease progression.
Neurodegeneration In The Ageing Brain: How The Pathways Leading To Aggregated Protein Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$12,322,838.00
Summary
The team consists of eight highly experienced research scientists who are dedicated to solving the question of how the brain degenerates in the elderly when associated with the accumulation of certain proteins: e.g. A_ amyloid (Alzheimer�s disease) and PrP (Creutzfeldt-Jakob disease). Understanding the molecular pathways leading to the degeneration (loss of neuronal synapses) will permit the development of rational diagnostic and therapeutic interventions. Over the past five years the program ha ....The team consists of eight highly experienced research scientists who are dedicated to solving the question of how the brain degenerates in the elderly when associated with the accumulation of certain proteins: e.g. A_ amyloid (Alzheimer�s disease) and PrP (Creutzfeldt-Jakob disease). Understanding the molecular pathways leading to the degeneration (loss of neuronal synapses) will permit the development of rational diagnostic and therapeutic interventions. Over the past five years the program has identified several diagnostic and therapeutic avenues which are now being developed by the Pharmaceutical and Biotechnology industries. Much more research is still required for maximizing the chances of success using these approaches.Read moreRead less
The Prevalence And Trajectory Of Kidney Disease In Urban Aboriginal Children
Funder
National Health and Medical Research Council
Funding Amount
$94,515.00
Summary
The Study of Environment and Aboriginal Resilience on Child Health is a major NHMRC funded project looking at the health and illness of urban Aboriginal children in Australia. By working together with Aboriginal Community Controlled Health Services across urban and large regional centres in NSW the study team hope to better understand the causes of common diseases such as kidney and heart disease, and whether these first begin in childhood.
Computational Modelling To Understand Early-stage Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Rather than attempting to reverse neurodegeneration, therapeutic strategies must target the earliest possible stages of disease, when treatments have the potential to prevent or slow down pathological progression. The proposed project will employ computational modelling using functional MRI to deliver highly efficient and sensitive markers of Familial Alzheimer’s disease and Huntington’s disease progression to inform when in the progression of disease clinical trials should take place.
The Causes, Treatment, And Prognosis Of Thyroid Disease
Funder
National Health and Medical Research Council
Funding Amount
$190,445.00
Summary
The thyroid gland controls body metabolism and is crucial to life. Disorders of the thyroid place a severe burden on the health system. Yet despite this, much is unknown about the causes, optimal treatments, and prognosis of thyroid disease. In this NHMRC Early Career Fellowship, Don aims to advance knowledge and improve treatments of these common conditions, focusing on thyroid cancer, Graves’ disease, and Hashimoto’s thyroiditis.
How The Environment And Epigenetics Affect The Brain Disease Gene, MAPT.
Funder
National Health and Medical Research Council
Summary
Genetic variants in the microtubule associated protein Tau (MAPT) gene are major risk factors for Alzheimer’s disease and Parkinson’s disease. Environmental or lifestyle factors, such as diet and smoking, have crucial roles in changing the risk of developing these diseases. These environmental factors may exert their influence via a mechanism known as "epigenetics". This project aims to determine whether the MAPT gene is susceptible to epigenetic changes by environmental factors, and whether thi ....Genetic variants in the microtubule associated protein Tau (MAPT) gene are major risk factors for Alzheimer’s disease and Parkinson’s disease. Environmental or lifestyle factors, such as diet and smoking, have crucial roles in changing the risk of developing these diseases. These environmental factors may exert their influence via a mechanism known as "epigenetics". This project aims to determine whether the MAPT gene is susceptible to epigenetic changes by environmental factors, and whether this process will have an impact on these diseases.Read moreRead less