Tissue Repair Unit
The words pulmonary fibrosis literally translates to lung scarring; the condition encompasses an abnormal formation of scar tissue in the lungs. The scar tissue builds up in the walls of the air sacs known as alveoli, and eventually makes it hard for air to pass through. Pulmonary fibrosis can be mild, severe or often life-threatening.
The cause of IPF is unknown but it is widely accepted that repeated injury to the epithelium leads to dysregulated healing, initiating a cascade of processes resulting in fibroblast / myofibroblast accumulation and overproduction and deposition of collagen.
The Tissue Repair Unit continues to pioneer studies in identifying the gp130-induced STAT3 signalling the pathway as pivotal in the development of lung fibrosis. What regulates STAT3-mediate fibrosis is not clear, but current studies are focusing on understanding the role of mediators known to activate the pathway, cell types that may be regulating the mediator response, as well as a possible breakdown in regulation of the naturally occurring inhibitors that normally control the STAT3 response.
Through a local, national and international collaboration, the Unit continues to investigate cross talk between epithelial cells and fibroblasts and the role this plays in the progression and development of fibrosis.
The Tissue Repair Group continue to dissect the molecular mechanisms and cell signalling pathways driving fibrosis, and together with collaborations at the University of Newcastle, are investigating mitochondrial dysfunction in IPF.
Current research projects
The Tissue Repair Group have an extensive programme of research which investigates the cellular and molecular pathways driving IPF. Notably, they have received NHMRC project grant funding for the following projects:
- STAT3 regulation of cell responses in IPF
- Epithelial-mesenchymal cell communication towards new therapeutic targets for fibrosis
- Fibroblast Scenecence as a driver of pulmonary fibrosis
- The Immune regulation of Idiopathic Pulmonary Fibrosis
The Tissue Repair team have several highlights for 2017/18. These include:
- The Australian Postgraduate Award Scholarship and the Lung Foundation Australia Bill van Nierop PhD Scholarship awarded to Tylah Miles.Awarded NHMRC Project Grant for research into epithelial-mesenchymal cell communication; towards new therapeutic targets for fibrosis.
- The Alan King Westcare Grant awarded for the effects of infection on mesothelial gene transcription: a role for immune check point regulation in chronic disease.
- Awarded the UHU Seed Funding Grant for investigating the role of specific B cell subsets in chronic lung disease.
- Awarded the UHU Collaborative Grant for Mesothelial cell involvement in serosal repair and adhesion formation.
- Celada LJ, Kropski JA, Herazo-Maya JD, Luo W, Creecy A, Abad AT, Chioma OS, Lee G, Hassell NE, Shaginurova GI, Wang Y, Johnson JE, Kerrigan A, Mason WR, Baughman RP, Ayers GD, Bernard GR, Culver DA, Montgomery CG, Maher TM, Molyneaux PL, Noth I, Mutsaers SE, Prele CM, Peebles RS Jr, Newcomb DC, Kaminski N, Blackwell TS, Van Kaer L, Drake WP. PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production. Sci Transl Med. 2018 Sep 26;10(460).
- Schuliga M, Pechkovsky DV, Read J, Waters DW, Blokland KEC, Reid AT, Hogaboam CM, Khalil N, Burgess JK, Prêle CM, Mutsaers SE, Jaffar J, Westall G, Grainge C, Knight DA. Mitochondrial dysfunction contributes to the senescent phenotype of IPF lung fibroblasts. J Cell Mol Med. 2018 Dec;22(12):5847-5861. doi: 10.1111/jcmm.13855. Epub 2018 Sep 26.
- Hynds RE, Gowers KHC, Nigro E, Butler CR, Bonfanti P, Giangreco A, Prêle CM, Janes SM. Cross-talk between human airway epithelial cells and 3T3-J2 feeder cells involves partial activation of human MET by murine HGF. PLoS One. 2018 May 17;13(5):e0197129.
- Waters DW, Blokland KEC, Pathinayake PS, Burgess JK, Mutsaers SE, Prele CM, Schuliga M, Grainge CL, Knight DA. Fibroblast senescence in the pathology of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2018 Aug 1;315(2):L162-L172. doi: 10.1152/ajplung.00037.2018. Epub 2018 Apr 26.
- Roman J, Mutsaers SE. Epigenetic Control of CXCL10: Regulating the Counterregulator in Idiopathic Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2018 Apr;58(4):419-420.