Dr Gang Liu obtained his Master of Science in Biotechnology in University of Wollongong (2011). He finished his PhD on immunology and microbiology at the University of Newcastle in 2016, and his PhD study is about extracellular matrix proteins regulate tissue remodelling in pulmonary diseases, including chronic obstructive pulmonary disease (COPD), asthma and idiopathic pulmonary fibrosis. He did his first postdoctoral training on mast cell regulates inflammation and airway remodelling in COPD in Priority Research Centre for Healthy Lung at University of Newcastle from 2016-2017. He then moved to gut disease research as a postdoctoral fellow at Priority Research Centre for Digestive Health and Neurogastroenterology at Hunter Medical Research Institute and University of Newcastle from 2017-2019, and his research was focusing on understanding of gut-lung axis in mucosal diseases and how microbiota changes affects gut diseases, such as inflammatory bowel disease. Now, Dr Liu is a lecturer in UTS. He is also a leader of fibrosis program in Centre for Inflammation, Centenary Institute and UTS. His current research to understand the mechanism of tissue remodelling/fibrosis and wound healing in different lung diseases. He also extends the fibrotic studies to the diseases in other organs, such as liver and gut.
Can supervise: YES
Tissue remodelling and fibrosis are a severe stage of many lung diseases, including chronic obstructive pulmonary disease (COPD), asthma and idiopathic pulmonary fibrosis (IPF). Current treatments only reduce symptoms but cannot halt and reverse fibrosis in these diseases. The most comment feature of lung remodelling is abnormal disposition of extracellular matrix (ECM) protein around airways and/or in the whole lung tissue, such as collagen. Fibulin-1 (Fbln1) is a key component of ECM proteins that have four variants in human (Fbln1a, b, c and d). I have generated Fbln1c gene knockout mice (these mice do not have Fbln1c gene), and these mice or normal mice received treatment to target to Fbln1c gene reduced lung remodelling and fibrosis in experimental models of COPD, asthma and lung fibrosis. These data suggest that Fbln1 may be a new therapeutic target to lung remodelling. Now, my research is to understand the mechanisms of Fbln1c regulates fibrosis/remodelling in these lung diseases using experimental models.
Lung and gut are the tissues that have similar mucosal structure. I extended my fibrosis and ECM protein research to gut diseases, such as inflammatory bowel disease (IBD) using experimental models of colitis in mice and clinical samples. I also try to understand gut and lung crosstalk and microbiota changes between these two organs during diseases.
Mast cells are important immune cells in human, and they release small particles, such as tryptases to regulate immune response. The role of these mast cell tryptases in lung diseases are not well understood. One of my researcher topics is to understand the role of these mast cell tryptases in lung diseases, such as COPD and IPF.
Immunology 1 (91401)
Ali, MK, Kim, RY, Brown, AC, Donovan, C, Vanka, KS, Mayall, JR, Liu, G, Pillar, AL, Jones-Freeman, B, Xenaki, D, Borghuis, T, Karim, R, Pinkerton, JW, Aryal, R, Heidari, M, Martin, KL, Burgess, JK, Oliver, BG, Trinder, D, Johnstone, DM, Milward, EA, Hansbro, PM & Horvat, JC 2020, 'Critical role for iron accumulation in the pathogenesis of fibrotic lung disease', JOURNAL OF PATHOLOGY, vol. 251, no. 1, pp. 49-62.View/Download from: Publisher's site
Ali, MK, Kim, RY, Brown, AC, Mayall, JR, Karim, R, Pinkerton, JW, Liu, G, Martin, KL, Starkey, MR, Pillar, AL, Donovan, C, Pathinayake, PS, Carroll, OR, Trinder, D, Tay, HL, Badi, YE, Kermani, NZ, Guo, Y-K, Aryal, R, Mumby, S, Pavlidis, S, Adcock, IM, Weaver, J, Xenaki, D, Oliver, BG, Holliday, EG, Foster, PS, Wark, PA, Johnstone, DM, Milward, EA, Hansbro, PM & Horvat, JC 2020, 'Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma', EUROPEAN RESPIRATORY JOURNAL, vol. 55, no. 4.View/Download from: Publisher's site
Hansbro, P, Donovan, C, Liu, G, Shen, S, Marshall, J, Kim, R, Alamao, CA, Budden, KF, Choi, JP, Kohonen-Corish, M, El-Omar, EM & Yang, IA 2020, 'The role of microbiome and NLRP3 inflammasome in the gut and the lung', Journal of Leukocyte Biology, vol. accepted 4.7.20.
Li, J, Xu, X, Jiang, Y, Hansbro, NG, Hansbro, PM, Xu, J & Liu, G 2020, 'Elastin is a key factor of tumor development in colorectal cancer', BMC CANCER, vol. 20, no. 1.View/Download from: Publisher's site
Liu, G, Baird, AW, Parsons, MJ, Fan, K, Skerrett-Byrne, DA, Nair, PM, Makanyengo, S, Chen, J, Neal, R, Goggins, BJ, Tay, H, Mathe, A, Soh, WS, Minahan, K, Hansbro, PM, Nixon, B, McCaughan, GW, Holtmann, G, Colgan, SP & Keely, S 2020, 'Platelet activating factor receptor acts to limit colitis-induced liver inflammation', FASEB JOURNAL.View/Download from: Publisher's site
Mehta, M, Satija, S, Paudel, KR, Liu, G, Chellappan, DK, Hansbro, PM & Dua, K 2020, 'Incipient need of targeting airway remodeling using advanced drug delivery in chronic respiratory diseases', Future Medicinal Chemistry, vol. 12, no. 10, pp. 873-875.View/Download from: Publisher's site
Xu, J, Xu, X, Jiang, L, Dua, K, Hansbro, PM & Liu, G 2020, 'SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis', RESPIRATORY RESEARCH, vol. 21, no. 1.View/Download from: Publisher's site
Findlay, AD, Foot, JS, Buson, A, Deodhar, M, Jarnicki, AG, Hansbro, PM, Liu, G, Schilter, H, Turner, CI, Zhou, W & Jarolimek, W 2019, 'Identification and Optimization of Mechanism-Based Fluoroallylamine Inhibitors of Lysyl Oxidase-like 2/3', JOURNAL OF MEDICINAL CHEMISTRY, vol. 62, no. 21, pp. 9874-9889.View/Download from: Publisher's site
Liu, G, Cooley, MA, Jarnicki, AG, Borghuis, T, Nair, PM, Tjin, G, Hsu, AC, Haw, TJ, Fricker, M, Harrison, CL, Jones, B, Hansbro, NG, Wark, PA, Horvat, JC, Argraves, WS, Oliver, BG, Knight, DA, Burgess, JK & Hansbro, PM 2019, 'Fibulin-1c regulates transforming growth factor-beta activation in pulmonary tissue fibrosis', JCI INSIGHT, vol. 4, no. 16.View/Download from: Publisher's site
Liu, G, Mateer, SW, Hsu, A, Goggins, BJ, Tay, H, Mathe, A, Fan, K, Neal, R, Bruce, J, Burns, G, Minahan, K, Maltby, S, Fricker, M, Foster, PS, Wark, PAB, Hansbro, PM & Keely, S 2019, 'Platelet activating factor receptor regulates colitis-induced pulmonary inflammation through the NLRP3 inflammasome.', Mucosal immunology, vol. 12, pp. 862-873.View/Download from: Publisher's site
Extra-intestinal manifestations (EIM) are common in inflammatory bowel disease (IBD). One such EIM is sub-clinical pulmonary inflammation, which occurs in up to 50% of IBD patients. In animal models of colitis, pulmonary inflammation is driven by neutrophilic infiltrations, primarily in response to the systemic bacteraemia and increased bacterial load in the lungs. Platelet activating factor receptor (PAFR) plays a critical role in regulating pulmonary responses to infection in conditions, such as chronic obstructive pulmonary disease and asthma. We investigated the role of PAFR in pulmonary EIMs of IBD, using dextran sulfate sodium (DSS) and anti-CD40 murine models of colitis. Both models induced neutrophilic inflammation, with increased TNF and IL-1β levels, bacterial load and PAFR protein expression in mouse lungs. Antagonism of PAFR decreased lung neutrophilia, TNF, and IL-1β in an NLRP3 inflammasome-dependent manner. Lipopolysaccharide from phosphorylcholine (ChoP)-positive bacteria induced NLRP3 and caspase-1 proteins in human alveolar epithelial cells, however antagonism of PAFR prevented NLRP3 activation by ChoP. Amoxicillin reduced bacterial populations in the lungs and reduced NLRP3 inflammasome protein levels, but did not reduce PAFR. These data suggest a role for PAFR in microbial pattern recognition and NLRP3 inflammasome signaling in the lung.
Nair, PM, Starkey, MR, Haw, TJ, Liu, G, Collison, AM, Mattes, J, Wark, PA, Morris, JC, Verrills, NM, Clark, AR, Ammit, AJ & Hansbro, PM 2019, 'Enhancing tristetraprolin activity reduces the severity of cigarette smoke-induced experimental chronic obstructive pulmonary disease', CLINICAL & TRANSLATIONAL IMMUNOLOGY, vol. 8, no. 10.View/Download from: Publisher's site
Haw, TJ, Starkey, MR, Pavlidis, S, Fricker, M, Arthurs, AL, Nair, PM, Liu, G, Hanish, I, Kim, RY, Foster, PS, Horvat, JC, Adcock, IM & Hansbro, PM 2018, 'Toll-like receptor 2 and 4 have opposing roles in the pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease', AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, vol. 314, no. 2, pp. L298-L317.View/Download from: Publisher's site
Mateer, SW, Mathe, A, Bruce, J, Liu, G, Maltby, S, Fricker, M, Goggins, BJ, Tay, HL, Marks, E, Burns, G, Kim, RY, Minahan, K, Walker, MM, Callister, RC, Foster, PS, Horvat, JC, Hansbro, PM & Keely, S 2018, 'IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis.', The American journal of pathology, vol. 188, no. 7, pp. 1625-1639.View/Download from: Publisher's site
Inflammatory bowel disease (IBD) is associated with several immune-mediated extraintestinal manifestations. More than half of all IBD patients have some form of respiratory pathology, most commonly neutrophil-mediated diseases, such as bronchiectasis and chronic bronchitis. Using murine models of colitis, we aimed to identify the immune mechanisms driving pulmonary manifestations of IBD. We found increased neutrophil numbers in lung tissue associated with the pulmonary vasculature in both trinitrobenzenesulfonic acid- and dextran sulfate sodium-induced models of colitis. Analysis of systemic inflammation identified that neutrophilia was associated with bacteremia and pyrexia in animal models of colitis. We further identified IL-6 as a systemic mediator of neutrophil recruitment from the bone marrow of dextran sulfate sodium animals. Functional inhibition of IL-6 led to reduced systemic and pulmonary neutrophilia, but it did not attenuate established colitis pathology. These data suggest that systemic bacteremia and pyrexia drive IL-6 secretion, which is a critical driver for pulmonary manifestation of IBD. Targeting IL-6 may reduce neutrophil-associated extraintestinal manifestations in IBD patients.
Nair, PM, Starkey, MR, Haw, TJ, Ruscher, R, Liu, G, Maradana, MR, Thomas, R, O'Sullivan, BJ & Hansbro, PM 2018, 'RelB-Deficient Dendritic Cells Promote the Development of Spontaneous Allergic Airway Inflammation', AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, vol. 58, no. 3, pp. 352-365.View/Download from: Publisher's site
Hansbro, PM, Kim, RY, Starkey, MR, Donovan, C, Dua, K, Mayall, JR, Liu, G, Hansbro, NG, Simpson, JL, Wood, LG, Hirota, JA, Knight, DA, Foster, PS & Horvat, JC 2017, 'Mechanisms and treatments for severe, steroid-resistant allergic airway disease and asthma.', Immunological reviews, vol. 278, no. 1, pp. 41-62.View/Download from: Publisher's site
Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid-resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes. This heterogeneity makes pinpointing processes that drive disease difficult in humans. Clinical studies strongly associate specific respiratory infections with severe, steroid-resistant asthma. In this review, we discuss key findings from our studies where we describe the development of representative experimental models to improve our understanding of the links between infection and severe, steroid-resistant forms of this disease. We also discuss their use in elucidating the mechanisms, and their potential for developing effective therapeutic strategies, for severe, steroid-resistant asthma. Finally, we highlight how the immune mechanisms and therapeutic targets we have identified may be applicable to obesity-or pollution-associated asthma.
Jones, B, Donovan, C, Liu, G, Gomez, HM, Chimankar, V, Harrison, CL, Wiegman, CH, Adcock, IM, Knight, DA, Hirota, JA & Hansbro, PM 2017, 'Animal models of COPD: What do they tell us?', Respirology, vol. 22, no. 1, pp. 21-32.View/Download from: Publisher's site
COPD is a major cause of global mortality and morbidity but current treatments are poorly effective. This is because the underlying mechanisms that drive the development and progression of COPD are incompletely understood. Animal models of disease provide a valuable, ethically and economically viable experimental platform to examine these mechanisms and identify biomarkers that may be therapeutic targets that would facilitate the development of improved standard of care. Here, we review the different established animal models of COPD and the various aspects of disease pathophysiology that have been successfully recapitulated in these models including chronic lung inflammation, airway remodelling, emphysema and impaired lung function. Furthermore, some of the mechanistic features, and thus biomarkers and therapeutic targets of COPD identified in animal models are outlined. Some of the existing therapies that suppress some disease symptoms that were identified in animal models and are progressing towards therapeutic development have been outlined. Further studies of representative animal models of human COPD have the strong potential to identify new and effective therapeutic approaches for COPD.
Liu, G, Cooley, MA, Nair, PM, Donovan, C, Hsu, AC, Jarnicki, AG, Haw, TJ, Hansbro, NG, Ge, Q, Brown, AC, Tay, H, Foster, PS, Wark, PA, Horvat, JC, Bourke, JE, Grainge, CL, Argraves, WS, Oliver, BG, Knight, DA, Burgess, JK & Hansbro, PM 2017, 'Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c.', The Journal of Pathology, vol. 243, no. 4, pp. 510-523.View/Download from: Publisher's site
Asthma is a chronic inflammatory disease of the airways. It is characterized by allergic airway inflammation, airway remodelling, and airway hyperresponsiveness (AHR). Asthma patients, in particular those with chronic or severe asthma, have airway remodelling that is associated with the accumulation of extracellular matrix (ECM) proteins, such as collagens. Fibulin-1 (Fbln1) is an important ECM protein that stabilizes collagen and other ECM proteins. The level of Fbln1c, one of the four Fbln1 variants, which predominates in both humans and mice, is increased in the serum and airways fluids in asthma but its function is unclear. We show that the level of Fbln1c was increased in the lungs of mice with house dust mite (HDM)-induced chronic allergic airway disease (AAD). Genetic deletion of Fbln1c and therapeutic inhibition of Fbln1c in mice with chronic AAD reduced airway collagen deposition, and protected against AHR. Fbln1c-deficient (Fbln1c-/- ) mice had reduced mucin (MUC) 5 AC levels, but not MUC5B levels, in the airways as compared with wild-type (WT) mice. Fbln1c interacted with fibronectin and periostin that was linked to collagen deposition around the small airways. Fbln1c-/- mice with AAD also had reduced numbers of α-smooth muscle actin-positive cells around the airways and reduced airway contractility as compared with WT mice. After HDM challenge, these mice also had fewer airway inflammatory cells, reduced interleukin (IL)-5, IL-13, IL-33, tumour necrosis factor (TNF) and CXCL1 levels in the lungs, and reduced IL-5, IL-33 and TNF levels in lung-draining lymph nodes. Therapeutic targeting of Fbln1c reduced the numbers of GATA3-positive Th2 cells in the lymph nodes and lungs after chronic HDM challenge. Treatment also reduced the secretion of IL-5 and IL-13 from co-cultured dendritic cells and T cells restimulated with HDM extract. Human epithelial cells cultured with Fbln1c peptide produced more CXCL1 mRNA than medium-treated controls. Our data show that...
Nair, PM, Starkey, MR, Haw, TJ, Liu, G, Horvat, JC, Morris, JC, Verrills, NM, Clark, AR, Ammit, AJ & Hansbro, PM 2017, 'Targeting PP2A and proteasome activity ameliorates features of allergic airway disease in mice.', Allergy, vol. 72, no. 12, pp. 1891-1903.View/Download from: Publisher's site
Asthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed whether enhancing PP2A activity with fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL(S) ), or inhibiting proteasome activity with bortezomib (BORT), could suppress experimental AAD.Acute AAD was induced in C57BL/6 mice by intraperitoneal sensitization with ovalbumin (OVA) in combination with intranasal (i.n) exposure to OVA. Chronic AAD was induced in mice with prolonged i.n exposure to crude house dust mite (HDM) extract. Mice were treated with vehicle, FTY720, AAL(S) , BORT or AAL(S) +BORT and hallmark features of AAD assessed.AAL(S) reduced the severity of acute AAD by suppressing tissue eosinophils and inflammation, mucus-secreting cell (MSC) numbers, type 2-associated cytokines (interleukin (IL)-33, thymic stromal lymphopoietin, IL-5 and IL-13), serum immunoglobulin (Ig)E and airway hyper-responsiveness (AHR). FTY720 only suppressed tissue inflammation and IgE. BORT reduced bronchoalveolar lavage fluid (BALF) and tissue eosinophils and inflammation, IL-5, IL-13 and AHR. Combined treatment with AAL(S) +BORT had complementary effects and suppressed BALF and tissue eosinophils and inflammation, MSC numbers, reduced the production of type 2 cytokines and AHR. AAL(S) , BORT and AAL(S) +BORT also reduced airway remodelling in chronic AAD.These findings highlight the potential of combination therapies that enhance PP2A and inhibit proteasome activity as novel therapeutic strategies for asthma.
Gold, MJ, Hiebert, PR, Park, HY, Stefanowicz, D, Le, A, Starkey, MR, Deane, A, Brown, AC, Liu, G, Horvat, JC, Ibrahim, ZA, Sukkar, MB, Hansbro, PM, Carlsten, C, VanEeden, S, Sin, DD, McNagny, KM, Knight, DA & Hirota, JA 2016, 'Mucosal production of uric acid by airway epithelial cells contributes to particulate matter-induced allergic sensitization.', Mucosal Immunology, vol. 9, no. 3, pp. 809-820.View/Download from: Publisher's site
Exposure to particulate matter (PM), a major component of air pollution, contributes to increased morbidity and mortality worldwide. PM induces innate immune responses and contributes to allergic sensitization, although the mechanisms governing this process remain unclear. Lung mucosal uric acid has also been linked to allergic sensitization. The links among PM exposure, uric acid, and allergic sensitization remain unexplored. We therefore investigated the mechanisms behind PM-induced allergic sensitization in the context of lung mucosal uric acid. PM10 and house dust mite exposure selectively induced lung mucosal uric acid production and secretion in vivo, which did not occur with other challenges (lipopolysaccharide, virus, bacteria, or inflammatory/fibrotic stimuli). PM10-induced uric acid mediates allergic sensitization and augments antigen-specific T-cell proliferation, which is inhibited by uricase. We then demonstrate that human airway epithelial cells secrete uric acid basally and after stimulation through a previously unidentified mucosal secretion system. Our work discovers a previously unknown mechanism of air pollution-induced, uric acid-mediated, allergic sensitization that may be important in the pathogenesis of asthma.
Haw, TJ, Starkey, MR, Nair, PM, Pavlidis, S, Liu, G, Nguyen, DH, Hsu, AC, Hanish, I, Kim, RY, Collison, AM, Inman, MD, Wark, PA, Foster, PS, Knight, DA, Mattes, J, Yagita, H, Adcock, IM, Horvat, JC & Hansbro, PM 2016, 'A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease', MUCOSAL IMMUNOLOGY, vol. 9, no. 4, pp. 859-872.View/Download from: Publisher's site
Jarnicki, AG, Schilter, H, Liu, G, Wheeldon, K, Essilfie, A-T, Foot, JS, Yow, TT, Jarolimek, W & Hansbro, PM 2016, 'The inhibitor of semicarbazide-sensitive amine oxidase, PXS-4728A, ameliorates key features of chronic obstructive pulmonary disease in a mouse model', BRITISH JOURNAL OF PHARMACOLOGY, vol. 173, no. 22, pp. 3161-3175.View/Download from: Publisher's site
Liu, G, Cooley, MA, Jarnicki, AG, Hsu, AC-Y, Nair, PM, Haw, TJ, Fricker, M, Gellatly, SL, Kim, RY, Inman, MD, Tjin, G, Wark, PAB, Walker, MM, Horvat, JC, Oliver, BG, Argraves, WS, Knight, DA, Burgess, JK & Hansbro, PM 2016, 'Fibulin-1 regulates the pathogenesis of tissue remodeling in respiratory diseases', JCI INSIGHT, vol. 1, no. 9.View/Download from: Publisher's site
Mayall, J, Hsu, A, Horvat, J, Daly, K, Chevalier, A, Gomez, H, Deane, A, Haw, T, Brown, A, Liu, G, Dua, K, Starkey, M, Kim, R, Mangan, N, Wark, P, Hertzog, P & Hansbro, P 2020, 'INTERFERON-EPSILON PROMOTES SUSCEPTIBILITY TO INFLUENZA A AND ASSOCIATED DISEASE', RESPIROLOGY, WILEY, pp. 80-80.
Liu, G, Mateer, S, Mathe, A, Goggins, B, Hsu, A, Minahan, K, Bruce, J, Fricker, M, Wark, P, Hansbro, P & Keely, S 2018, 'Platelet Activating Factor Receptor (PAFR) Regulates Colitis-induced Pulmonary Inflammation', FASEB JOURNAL, Annual Meeting of Amer-Assoc-of-Anatomists (AAA), Amer-Physiol-Soc (APS), Amer-Soc-for-Biochemistry-and-Mol-Biol (ASBMB), Amer-Soc-for-Investigat-Pathol (ASIP), Amer-Soc-for-Pharmacol-and-Experimental-Therapeut (ASPET) on Experimental Biology (EB), FEDERATION AMER SOC EXP BIOL, Amer Assoc Anatomists, San Diego, CA.
Horvat, JC, Ali, MK, Johnstone, D, Kim, RY, Mayall, JR, Karim, R, Pinkerton, JW, Heidari, M, Martin, KL, Donovam, C, Liu, G, Milward, EA & Hansbro, PM 2017, 'Role for dysregulated iron in the pathogenesis of murine models of lung disease', JOURNAL OF IMMUNOLOGY, Annual Meeting of the American-Association-of-Immunologists (AAI), AMER ASSOC IMMUNOLOGISTS, Washington, DC.