Relaxin-Fibrosis Laboratory
Laboratory Head
Contact Details
E-mail: | |
Phone: | +61 3 8344 0416 (direct) / 8344 1888 (main) |
Fax: | +61 3 9348 1707 |
Number of
Staff: 1
- Ms Chong Xin (Stella) Zhao MSc chongxin.zhao@florey.edu.au
Students: 2
- PhD students
- Ms Ishanee Mookerjee BSc (Hons)
- Ms Su Ee Wong BBSc BSc (Hons)
Research Interests
The peptide hormone relaxin plays a number of important physiological roles within the body, many of which are associated with its ability to stimulate collagen remodelling in several of the major organs during growth/development and pregnancy. It is well established that relaxin’s ability to regulate collagen turnover is essential for softening the pelvic ligaments and female reproductive organs in preparation for child birth. Furthermore, studies from our laboratory have established that relaxin is potent, but safe anti-fibrotic (anti-scarring) agent, by inhibiting collagen deposition (a major component of scar tissue). We have also shown that relaxin acts at multiple levels to inhibit collagen synthesis and enhance collagen degradation.
We are currently using models of ischemic and hypertensive heart disease, allergic airways disorders (such as asthma), obstructive renal disease and diabetes to investigate the therapeutic potential of relaxin; the primary focus being to establish the anti-fibrotic and regenerative capacity of the peptide hormone. Furthermore, we are currently using relaxin gene-knockout and relaxin receptor (RXFP1) gene-knockout mice to determine the significance of endogenous relaxin. Both these knockout models demonstrate an age-related progression of fibrosis and a more rapid accumulation of tissue collagen, when subjected to injury, demonstrating the importance of the relaxin-RXFP1 interaction in regulating the progression of fibrosis. The influence of gender and the signalling mechanisms involved with relaxin’s ability to regulate collagen turnover are also being studied.
Current Projects
- Investigating the therapeutic effects of relaxin in the heart (in collaboration with Dr Xiao-Jun Du, Baker Heart Research Institute)
- Using several experimental models of human cardiovascular disease, we are currently determining the matrix remodelling, anti-fibrotic, anti-hypertrophic, anti-apoptotic and regenerative effects of relaxin in vivo. Additionally, in vitro studies using cardiac fibroblasts are being used to aid our understanding of the mechanism of relaxin’s actions in the diseased myocardium.
- Establishing the therapeutic significance of relaxin in renal disease (in collaboration with Dr Tim Hewitson, Department of Nephrology, Royal Melbourne Hospital)
- The therapeutic effects of relaxin in experimental models of human renal disease are being studied. Additionally, relaxin and relaxin receptor gene-knockout mice are currently being used to understand the significance of endogenous relaxin in the ageing and diabetic kidney, in addition to its role in the process of tubulointerstitial fibrosis (a hallmark of most forms of renal disease).
- Understanding the role of relaxin in allergic airways disorders (asthma) (in collaboration with A/Prof Mimi Tang, Departments of Allergy & Immunology, Royal Children’s Hospital)
- Relaxin and relaxin receptor gene-knockout mice are currently being subjected to models of allergic airways disease, to understand the significance of endogenous relaxin in the pathological airways/lung. More specifically, the role of relaxin in regulating airway remodelling, fibrosis, inflammation and hyperresponsiveness (AHR) are currently being investigated. The effects of relaxin therapy on these various parameters are also being studied in these models.
- Determining the signalling mechanisms of relaxin’s anti-fibrotic actions (in collaboration with Professor Roger Summers, Department of Pharmacology, Monash University; and Dr Ross Bathgate, HFI)
- Using fibroblast cell lines and primary fibroblast cultures which naturally express the relaxin receptor, we are currently investigating the signalling pathways by which relaxin induces its matrix remodelling actions. The pathways involved in relaxin’s ability to regulate myofibroblast and collagen accumulation, in addition to matrix metalloproteinase (MMP) stimulation are currently being investigated.
- Protein profiling of experimental models of fibrosis (in collaboration with Dr Eleni Giannakis and A/Prof John Wade, HFI)
- Using Ciphergen protein array technology, we are currently profiling the various proteins that are altered in response to fibrotic injury, as a means of identifying novel biomarkers that are associated with the progression of disease. Similarly, identifying novel proteins that are altered following relaxin treatment of experimental models of fibrosis will aid our studies on determining the mechanism of relaxin’s anti-fibrotic actions.
Laboratory Techniques
- Animal surgery/pathophysiology
- Functional studies
- Protein biochemistry
- Molecular biology
- Histology/immunohistochemistry
- Cell biology
Funding
- Australian Research Council
- Australian Stem Cell Centre
- BAS Medical
- National Heart Foundation of Australia (NHFA)
- National Health & Medical Research Council (NHMRC) of Australia
Additonal Information
Please see PubMed.
Research
