Tissue Repair and Fibrosis Group

The Group aims to better understand the role of the immune response in the development of lung fibrosis and how changes in immunity impact disease progression. Studies conducted by the team have demonstrated that immune cell composition is altered in patients with IPF, with significant immune dysfunction identified in a subset of individuals. The team is currently investigating immune biomarkers as potential diagnostic tools for IPF, as well as the utility of immunomodulatory strategies for the treatment of lung fibrosis.

The Group has previously demonstrated a role for B cells in the development of fibrosis. There has been much interest in the contribution of immune cells to fibrotic disease progression, with evidence of increased B-cell number, activating factors, and B-cell-associated chemokines reported for interstitial lung diseases. A Phase I clinical trial in IPF has shown promising results demonstrating improved lung function in patients with severe disease following B-cell depletion therapy. However, the specific role of B cells and other immune cells in fibrosis is unclear. The group is currently using a combination of clinical samples and preclinical models to understand the changes in immune composition and the role of the immune system in fibrosis.

Idiopathic pulmonary fibrosis is defined as a heterogeneous disease, characterised by distinct and variable disease trajectories. The team have identified that nearly a quarter of patients with IPF exhibit an immunophenotype resembling that observed in autoimmune disease. Using an Australian-based discovery cohort, the team identified a number of unique circulating peptides (putative auto-antigens) in IPF and is currently validating their diagnostic potential in a second patient cohort. This work aims to support the development of a diagnostic tool to stratify patients for targeted treatment, ultimately improving future clinical management.

Cochlear implants restore hearing in individuals with severe to profound deafness. However, outcomes vary. This variability has been associated with scar tissue formation (fibrosis) around the implant electrode. The team are developing and testing novel therapeutic approaches to limit the development and impact of fibrosis in the inner ear following cochlear implantation. They have recently demonstrated that an anti-fibrotic drug, previously approved for the treatment of IPF, can be successfully delivered to the inner ear and effectively reduce cochlear implant-induced fibrosis in preclinical models. They are currently developing cellular models of inner fibrosis in vitro and are investigating disease pathogenesis using molecular approaches, which will identify novel therapeutic targets aimed at improving the reliability of cochlear implants following surgery.

The team has also recently joined the national TRACKER Biobank study as the WA sample processing site. TRACKER is Australia’s first open-access national lung cancer biobank, created to accelerate discovery and transform outcomes for people affected by the world’s deadliest cancer. Proudly co-designed with people who have lived experience from across the country, TRACKER is built on partnership, inclusivity, and real-world impact.

By collecting, curating, and sharing biological samples linked to detailed clinical and outcome data, TRACKER enables high-quality, innovative research. Through national collaboration with clinicians, researchers, and industry partners, TRACKER supports studies in early detection, treatment response, side effects, and disease progression; translating scientific insight into better prevention, earlier diagnosis, and more effective treatments for all Australians affected by lung cancer, regardless of background, location, or circumstances.

2020

• Prêle, C. M., & Hoyne, G. F. Immunopathobiology of chronic lung disease. Clinical & Translational Immunology. 2020;9(8):e.1170.
• Blokland, K. E. C., Waters, D. W., Schuliga, M., Read, J., Pouwels, S. D., Grainge, C. L., Jaffar, J., Westall, G., Mutsaers, S. E., Prêle, C. M., Burgess, J. K., & Knight, D. A. Senescence of IPF lung fibroblasts disrupt Alveolar Epithelial Cell Proliferation and promote migration in wound healing. Pharmaceutics. 2020;12(4):389.
• Schuliga, M., Read, J., Blokland, K. E. C., Waters, D. W., Burgess, J., Prêle, C., Mutsaers, S. E., Jaffar, J., Westall, G., Reid, A., James, A., Grainge, C., & Knight, D. A. Self DNA perpetuates IPF lung fibroblast senescence in a cGAS-dependent manner. Clinical Science. 2020;134(7):889–905.
• Johnson, B. Z., Stevenson, A. W., Prêle, C. M., Fear, M. W., & Wood, F. M. The role of IL-6 in skin fibrosis and cutaneous wound healing. Biomedicines. 2020;8(5):101.
• Miles, T., Hoyne, G. F., Knight, D. A., Fear, M. W., Mutsaers, S. E., & Prêle, C. M. The contribution of animal models to understanding the role of the immune system in human idiopathic pulmonary fibrosis. Clinical & Translational Immunology. 2020;9(7):e1153.
• Deng, Z., Fear, M. W., Suk Choi, Y., Wood, F. M., Allahham, A., Mutsaers, S. E., & Prêle, C. M. The extracellular matrix and mechanotransduction in pulmonary fibrosis. The International Journal of Biochemistry & Cell Biology. 2020;126:105802.
• Mutsaers, S. E., Pixley, F. J., Prêle, C. M., & Hoyne, G. F. Mesothelial cells regulate immune responses in health and disease: Role for immunotherapy in malignant mesothelioma. Current Opinion in Immunology. 2020;64:88–109.
• Alghamdi, M. A., Wallace, H. J., Melton, P. E., Moses, E. K., Stevenson, A., Al-Eitan, L. N., Rea, S., Duke, J. M., Danielsen, P. L., Prêle, C. M., Wood, F. M., & Fear, M. W. Identification of differentially methylated CpG Sites in fibroblasts from Keloid Scars. Biomedicines. 2020;8(7):181.

2019

• Birnie, K. A., Prêle, C. M., Musk, A. W., de Klerk, N., Lee, Y. C. G., Fitzgerald, D., Allcock, R. J. N., Thompson, P. J., Creaney, J., Badrian, B., & Mutsaers, S. E. MicroRNA signatures in malignant pleural mesothelioma effusions. Disease Markers. 2019:1–9.
• Abayasiriwardana, K. S., Wood, M. K., Prêle, C. M., Birnie, K. A., Robinson, B. W., Laurent, G. J., McAnulty, R. J., & Mutsaers, S. E. Inhibition of collagen production delays malignant mesothelioma tumor growth in a murine model. Biochemical and Biophysical Research Communications. 2019;510(2):198–204.
• Moore, C., Blumhagen, R. Z., Yang, I. V., Walts, A., Powers, J., Walker, T., Bishop, M., Russell, P., Vestal, B., Cardwell, J., Markin, C. R., Mathai, S. K., Schwarz, M. I., Steele, M. P., Lee, J., Brown, K. K., Loyd, J. E., Crapo, J. D., Silverman, E. K., et al. Resequencing study confirms that host defense and cell senescence gene variants contribute to the risk of idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine. 2019;200(2):199–208.
• Waters, D. W., Blokland, K. E. C., Pathinayake, P. S., Wei, L., Schuliga, M., Jaffar, J., Westall, G. P., Hansbro, P. M., Prêle, C. M., Mutsaers, S. E., Bartlett, N. W., Burgess, J. K., Grainge, C. L., & Knight, D. A. STAT3 Regulates the Onset of Oxidant-induced Senescence in Lung Fibroblasts. American Journal of Respiratory Cell and Molecular Biology. 2019;61(1):61–73.
• Wijeratne, D., Rodger, J., Stevenson, A., Wallace, H., Prele, C. M., Wood, F. M., & Fear, M. W. Ephrin-A2 affects wound healing and scarring in a murine model of excisional injury. Burns. 2019;45(3):682–690.

2018

• Schuliga, M., Pechkovsky, D. V., Read, J., Waters, D. W., Blokland, K. E. C., Reid, A. T., Hogaboam, C. M., Khalil, N., Burgess, J. K., Prêle, C. M., Mutsaers, S. E., Jaffar, J., Westall, G., Grainge, C., & Knight, D. A. Mitochondrial dysfunction contributes to the senescent phenotype of IPF lung fibroblasts. Journal of Cellular and Molecular Medicine. 2018;22(12):5847–5861.
• Celada, L. J., Kropski, J. A., Herazo-Maya, J. D., Luo, W., Creecy, A., Abad, A. T., Chioma, O. S., Lee, G., Hassell, N. E., Shaginurova, G. I., Wang, Y., Johnson, J. E., Kerrigan, A., Mason, W. R., Baughman, R. P., Ayers, G. D., Bernard, G. R., Culver, D. A., Montgomery, C. G., et al. PD-1 up-regulation on CD4 + T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production. Science Translational Medicine. 2018;10(460):eaar8356.
• Waters, D. W., Blokland, K. E. C., Pathinayake, P. S., Burgess, J. K., Mutsaers, S. E., Prêle, C. M., Schuliga, M., Grainge, C. L., & Knight, D. A. Fibroblast senescence in the pathology of idiopathic pulmonary fibrosis. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2018;315(2):L162–L172.
• Hynds, R. E., Gowers, K. H. C., Nigro, E., Butler, C. R., Bonfanti, P., Giangreco, A., Prêle, C. M., & Janes, S. M. Cross-talk between human airway epithelial cells and 3T3-J2 feeder cells involves partial activation of human MET by murine HGF. PLoS ONE. 2018;13(5):e0197129.

2017

• Birnie, K. A., Prêle, C. M., Thompson, P. J., Badrian, B., & Mutsaers, S. E. Targeting microRNA to improve diagnostic and therapeutic approaches for malignant mesothelioma. Oncotarget. 2017;8(44):78193–78207.
• Hoyne, G. F., Elliott, H., Mutsaers, S. E., & Prêle, C. M. Idiopathic pulmonary fibrosis and a role for autoimmunity. Immunology & Cell Biology. 2017;95(7):577–583.

2016

• Mutsaers, S. E., Jaurand, M.-C., Lee, Y. C. G., & Prêle, C. M. Mesothelial cells and pleural immunology. In R. W. Light & Y. C. G. Lee (Editors), Textbook of Pleural Diseases (pp. 51–68). CRC Press. 2016.
• Mutsaers, S. E., Prêle, C. M., Pengelly, S., & Herrick, S. E. Mesothelial cells and peritoneal homeostasis. Fertility and Sterility. 2016;106(5):1018–1024.
• Lansley, S. M., Pedersen, B., Robinson, C., Searles, R. G., Sterrett, G., van Bruggen, I., Lake, R. A., Mutsaers, S. E., & Prêle, C. M. A subset of malignant mesothelioma tumors retain osteogenic potential. Scientific Reports. 2016;6(1):36349.