Detecting Bioactivity In A Naturally-occurring Aggrecan Fragment
Funder
National Health and Medical Research Council
Funding Amount
$407,634.00
Summary
The dynamic balance of anabolic and catabolic processes in healthy cartilage is disturbed in arthritis, with increased catabolism leading to irreparable cartilage damage. We will study the ability of a naturally-occuring aggrecan fragment to modulate cartilage catabolism. Our in vitro and in vivo experiments suggest that the aggrecan fragment limits cartilage destruction. This study tests our hypothesis that the aggrecan fragment antagonises cartilage damage and promote cartilage repair.
Modulating Inflammatory And Fibrogenic Pathways In Kidney Disease Using A Novel Antagonist Of Protease-Activated-Receptor-2
Funder
National Health and Medical Research Council
Funding Amount
$581,116.00
Summary
Chronic kidney disease (CKD) now affects 10% of adults in industrialised countries. Current treatments are largely ineffective. Thus developing better CKD treatments will have substantial public health benefit. Three well established and clinically relevant animal models of kidney disease will be used to test the ability of a new experimental anti-inflammatory drug, developed by members of this research team at The University of Queensland, to prevent or lessen the progression of CKD.
Obesity increases the risk of developing diseases such as heart disease and type 2 diabetes, however not all obese people develop such diseases. Obese subjects with small fat cells are typically healthier than those with fewer, large fat cells. The applicants have identified a novel pathway that promotes the generation of new fat cells. This project will increase understanding of this pathway and may, ultimately, lead to new therapies that manipulate fat cell number and reduce obesity related di ....Obesity increases the risk of developing diseases such as heart disease and type 2 diabetes, however not all obese people develop such diseases. Obese subjects with small fat cells are typically healthier than those with fewer, large fat cells. The applicants have identified a novel pathway that promotes the generation of new fat cells. This project will increase understanding of this pathway and may, ultimately, lead to new therapies that manipulate fat cell number and reduce obesity related disease.Read moreRead less
Defining The Mechanisms Regulating Tissue Mechano-reciprocity In Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$624,488.00
Summary
Wound healing is slow in people with diseases including diabetes or reduced blood circulation to the limbs. Wounds that remain unhealed for a long time may require surgery and limb amputations, often leading to disability and premature death, while costing the health system $3 billion/yr. We have found that wound healing can be accelerated more than 2-fold by the inhibition of a protein called 14-3-3zeta, and seek to find out how this occurs so that it may be exploited for therapy.
EFFECT OF LIPOXIN A4 AND PROSTAGLANDIN E2 IN ASSISSTED BONE HEALING
Funder
National Health and Medical Research Council
Funding Amount
$118,796.00
Summary
Bone healing and repair following trauma involves a complex series of events at both the cellular and molecular levels. This study aims to determine that local application of optimal dose of lipoxin A4 (promote resolution of inflammation) and prostaglandin E2 (low dosage stimulating localised bone formation) will promote healing following the placement of polymer foam in the defect, there by develop a therapy where bone deposition is accelerated and healing is enhanced.
Transforming Growth Factor Beta Signalling In Malignant Mesothelioma Growth And Collagen Production
Funder
National Health and Medical Research Council
Funding Amount
$509,917.00
Summary
Many cancers contain abundant connective tissue molecules called extracellular matrix (ECM) and data show that interaction of ECM with cells are important in the growth of cancers (1). Changes in expression of ECM and their receptors (integrins) have been associated with malignant changes in cells, enhanced tumour growth and resistance to chemotherapy (2,3). We have recently shown that inhibition of collagen, the most abundant ECM molecule produced by malignant mesothelioma (MM) cells, reduced M ....Many cancers contain abundant connective tissue molecules called extracellular matrix (ECM) and data show that interaction of ECM with cells are important in the growth of cancers (1). Changes in expression of ECM and their receptors (integrins) have been associated with malignant changes in cells, enhanced tumour growth and resistance to chemotherapy (2,3). We have recently shown that inhibition of collagen, the most abundant ECM molecule produced by malignant mesothelioma (MM) cells, reduced MM growth. How cancer cells regulate ECM production and control their growth is unclear but strong evidence suggests the growth factor transforming growth factor-beta (TGFB) plays an important role. We and others showed that MM cells secrete all forms (1-3) of TGFB, and TGFB1,2-like activity has been reported in pleural effusions from MM (4,5). All TGFB forms stimulate MM cells to grow and make ECM (6,7). We showed that high levels of collagen produced by MM are enhanced by TGFB. Small molecules called antisense oligonucleotides (AO) which blocked production of TGFB2 by cells, reduced MM cell growth in soft agar, a characteristic of cancer, and partially blocked MM growth in animal models (4,6). This was supported by studies using soluble TGFB type II receptors, which blocks TGFB1,3 (8), and our studies using TGFB2 specific antibodies, as both studies reduced tumour growth. These findings support a role for TGFB in MM growth. However, all TGFB forms can promote cell grow and collagen synthesis and therefore ways to block all TGFB forms are required to ensure maximal effect. This study will examine the effect of blocking common downstream signalling pathways of all three TGFB isoforms on MM collagen production and tumour growth. These pathways are activated when TGFB binds to its receptors sending messages to the nucleus of the cell to make collagen or grow. By identifying which TGFB signalling pathway is important, we may be able to design novel therapeutic approaches to help treat patients with this disease.Read moreRead less