Molecular Mechanisms Of Joint Degeneration In Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$718,273.00
Summary
Arthritis is a major clinical and socio-economic problem. Arthritis involves the destruction of cartilage in joints. However, the mechanisms of initiation and progression of cartilage destruction remain poorly understood. Our studies will for explore the role of a new regulator of gene expression, microRNA, in the initation and progression of osteoarthritis. This will provide important new information on disease mechanisms for the development of diagnostic biomarkers and therapies
Investigating Deregulation Of Mitosis As A Mechanism Of Tumourigenesis In MYCN-driven Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$372,298.00
Summary
Neuroblastoma chemotherapy often only works temporarily because a small number of tumour cells can resist drugs and eventually regrow as a new tumour. These resistant cells resemble the very first cells that turn into a cancer cell at tumour initiation. We have used single cell technology to uncover genetic markers of tumour initiating cells. In this project we will determine how these marker genes cause tumour initiation and develop therapies that target them in drug resistant neuroblastoma.
Mechanistic And Functional Drivers Of Neochromosome Evolution
Funder
National Health and Medical Research Council
Funding Amount
$763,771.00
Summary
Neochromosomes are Frankenstein chromosomes--massive extra chromosomes that are stitched together from 100s of pieces of normal chromosomes. They are found in 3% of cancers, but are common in some types, such as liposarcoma. We have mapped their structure and found they form through punctuated chromosome shattering and gene amplification. We will investigate the precise molecular mechanisms that cause this and the recurrent transcriptional and epigenetic drivers lead to their formation.
Are Chondrocytes The Target Cells Of Glucocorticoid Therapy In Autoimmune Arthritis?
Funder
National Health and Medical Research Council
Funding Amount
$544,619.00
Summary
Glucocorticoids (GCs) are widely used for their potent anti-inflammatory and immunomodulatory effects due to the effects GCs on immune cells or synovial fibroblasts. Recently, we have made the exciting discovery that arthritis mice with glucocorticoid receptor knock-out in chondrocyte are completely resistant to glucocorticoid treatment. This study will identify the mechanisms underlying these hormonal effects with the aim to find new targets for efficient treatments for arthritis.
Optimising Non-invasive Ventilation At Birth For Preterm Infants
Funder
National Health and Medical Research Council
Funding Amount
$735,912.00
Summary
Infants born very premature require respiratory support at birth to make the transition to newborn life. As these infants are very immature and prone to injury, modern respiratory care strategies utilise the least invasive approaches mainly applied using a facemask. However, we have discovered that the larynx is closed at birth and thereby prevents air from entering the lung. This application is focussed on optimising the efficiency of facemask ventilation at birth and stimulating breathing.
Assessment Of Markers Of Genomic Instability For The Prediction Of Treatment Response In Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$590,086.00
Summary
The success of therapy for patients with chronic myeloid leukaemia depends on close monitoring during therapy for early recognition of pending relapse, and the selection of appropriate treatment if drug resistance occurs. This project aims to identify patients at the start of therapy who are at risk of treatment failure by investigating their genetic profile. An increased frequency of gene mutations may indicate that patients require more aggressive therapy to achieve an optimal response.
Osteoarthritis (OA) affects approximately 20% of Australians and costs billions each year in joint replacements. Therapies that halt joint destruction in OA are urgently needed. We hypothesise that the little-known gene, vanin -3, is a key regulator of OA disease pathways. Our project will map vanin-3 in the joint and reveal how much vanin-3 contributes to joint destruction in mice. We expect to find a link between vanin-3 and metabolic disorders and identify new targets for therapy.
Femoroacetabular impingement (FAI) is a common cause of hip pain characterised by extra bone formation at the hip, called a cam-deformity. FAI is thought to create hip joint damage and osteoarthritis. Our 5 year longitudinal study of people with FAI in two (Melbourne and Brisbane) sites will investigate whether factors (such as cam-deformity size, hip contact force, muscle strength and joint range) can predict hip joint damage (measured with magnetic resonance imaging) over two years.
MicroRNAs As Therapeutic Targets For Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$921,754.00
Summary
microRNAs are small cellular RNA fragments that regulate protein expression. They have been shown to be crucial regulators of normal development and are associated with many disease processes. The goal of this project is to determine the role of microRNAs in the initiation and progression of joint degeneration in osteoarthritis and test the therapeutic efficacy of targeting microRNAs as new approach to OA treatment.
Improving Treatment Of Non-small Cell Lung Cancer: Suppressing Cell Division Cycle Associated Protein 3 (CDCA3)
Funder
National Health and Medical Research Council
Funding Amount
$194,446.00
Summary
Lung cancer is the leading cause of cancer-related mortality worldwide. This project will establish the worth of suppressing the molecule ‘cell division cycle associated protein 3’ (CDCA3) in lung cancer. To do so, we will adjust the levels of CDCA3 in animal lung cancer models and treat the tumours with chemotherapy and the novel drug CX-4945. We expect that reduced levels of CDCA3 combined with CX-4945 and/or chemotherapy in NSCLC patients will benefit patient outcome.