Dr Michael Schuliga
Postdoctoral Research Associate
School of Biomedical Sciences and Pharmacy
- Email:michael.schuliga@newcastle.edu.au
- Phone:(02) 40420845
Career Summary
Biography
Dr Michael Schuliga is a University of Newcastle researcher with extensive experience investigating lung cell biology and the effects of therapeutics in lung injury and disease. Based at the Hunter Medical Research Institute (HMRI), he is currently advancing research into the lethal lung disease, idiopathic pulmonary fibrosis (IPF). Dr Schuliga aims to better understand the role of ageing mechanisms such as senescence and mitochondrial dysfunction in the pathology of age-related lung diseases such as IPF.
Dr. Schuliga is an honours graduate of the University of Melbourne, where he also had a 14 year stint as a post-doc in the Dept. of Pharmacology & Therapeutics (2002-2016). There he implemented advanced molecular biology and proteomic procedures in respiratory disease and cancer research. During this time he was involved in commercial translational studies with small Biotech elucidating the binding targets of novel anti-fibrotics. He was also a principal- and co-investigator of NHMRC-funded lung cell-molecular pharmacology research. Dr Schuliga is well networked in the lung fibrosis research community, currently advancing IPF research in team with Prof Darryl Knight and A/Prof Chris Grainge. His pioneering research is highlighted by his numerous first- or senior-author original research publications in the premier specialist respiratory, clinical and pharmacology journals (ie British J Pharmacol, Am J Respir Cell Mol Biol, Am J Physiol Lung Cell Mol Physiol, J Cell Mol Med and Clinical Sciences). Dr Schuliga’s increasing research profile is also highlighted by his invited reviews in Chest, Current Opinion in Pharmacology, Pulmonary Pharmacology & Therapeutics, Mediators of Inflammation, Int J Biochem Cell Biol and Biomolecules. He currently has >2150 citations with a h-index of 26 (My Citations, Google, March 2022) and is a member of the editorial board for Am J Physiol Lung Cell Mol Physiol. Dr Schuliga has presented his research at international meetings such as the Young Investigator’s International Smooth Muscle Symposia, the British Association of Lung Research (BALR) Respiratory Genetics Meeting, the Groningen Research Institute of Asthma and COPD (Netherlands) and the (bi)annual meetings of the European Respiratory Society (ERS), American Thoracic Society (ATS) and the International Colloquium on Lung and Airway Fibrosis (ICLAF). He also regularly presents, judges and chairs sessions at national conferences including the Australian Rare Lung Disease Short Course (ARLDSC) and the annual scientific meetings of theAustralian Society of Clinical and Experimental Pharmacologists and Toxicologists(ASCEPT), the Australian Health and Medical Research Council (AHMRC) and the Thoracic Society of Australia and New Zealand (TSANZ). Dr Schuliga has been a recipient of numerous small awards and grants including the ATS International Travel Trainee Scholar Award, the BALR Travel Award, a Helen Macpherson Smith Trust Award by the Asthma Foundation of Victoria, a John Hunter Hospital Charitable Trust Grant, a Lung Foundation Australia (LFA) Lizotte Family IPF Research Grant and a LFA, Eleanor Greenwood Memorial Travel Grant. He currently has a lead role in a collaborative research project with the pharmaceutical company, Boehringer Ingelheim that involves the development of models used in investigations of lung injury and disease.
Qualifications
- Doctor of Philosophy, Deakin University
- Bachelor of Science, University of Melbourne
- Graduate Diploma in Education (Secondary), Monash University
Keywords
- Ageing
- Idiopathic pulmonary fibrosis
- Senescence
- Urokinase plasminogen activator
- fibroblasts
- lung disease
- mitochondrial dysfunction
- pharmacology
- tissue remodelling
Fields of Research
Code | Description | Percentage |
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320103 | Respiratory diseases | 100 |
Professional Experience
UON Appointment
Title | Organisation / Department |
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Postdoctoral Research Associate | University of Newcastle School of Biomedical Sciences and Pharmacy Australia |
Awards
Award
Year | Award |
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2018 |
Eleanor Greenwood Memorial Travel Grant Lung Foundation Australia |
2018 |
PRC for Healthy Lungs Travel Award Priority Research Centre (PRC) for Healthy Lungs | The University of Newcastle |
2009 |
Helen Macpherson Smith Trust Award by Asthma Foundation of Victoria Asthma Foundation of Victoria |
2008 |
American Thoracic Society International Travel Trainee Scholar Award American Thoracic Society |
Prize
Year | Award |
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2017 |
Australian Rare Lung Disease Short Course, Best Scientific Abstract The Australian Lung foundation |
2016 |
1st prize of the ILD Session (Oral Communication) at the TSANZ NSW Branch ASM (2016) The Thoracic Society of Australia & New Zealand |
2014 |
Travel Award by the British Association of Lung Research (BALR) (2014) British Lung Foundation |
2011 |
1st prize Scientific Session, TSANZ Vic Branch ASM TSANZ Vic Branch ASM |
Research Award
Year | Award |
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2017 |
Lung Foundation Australia, Lizotte Family IPF Research Award Lung Foundation Australia |
Publications
For publications that are currently unpublished or in-press, details are shown in italics.
Chapter (5 outputs)
Year | Citation | Altmetrics | Link | ||
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2015 |
Schuliga M, 'Airway smooth muscle, matrix and proteases: Therapeutic implications', Muscle Cell and Tissue, InTech, Online (2015)
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2011 |
Stewart AG, Soon L, Schuliga M, 'Fibroblasts', Inflammation and Allergy Drug Design 149-162 (2011)
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2010 | Schuliga M, Braet F, Soon LL, Stewart AG, Chien H-Y, Ratinac KR, 'The benefits of microfluidics for imaging cell migration', Microscopy: Science, Technology, Applications and Education., Formatex Research Centre, Spain 1146-1154 (2010) | ||||
Show 2 more chapters |
Journal article (50 outputs)
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2022 |
Schuliga M, Madala SK, 'ASK1ng to Delay the Progression of Pulmonary Fibrosis', AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 66 465-467 (2022)
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2022 |
George PM, Reed A, Desai SR, Devaraj A, Faiez TS, Laverty S, et al., 'A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae', SCIENCE TRANSLATIONAL MEDICINE, 14 (2022) [C1]
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2022 |
Blokland KEC, Nizamoglu M, Habibie H, Borghuis T, Schuliga M, Melgert BN, et al., 'Substrate stiffness engineered to replicate disease conditions influence senescence and fibrotic responses in primary lung fibroblasts', Frontiers in Pharmacology, 13 [C1]
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2021 |
Blokland KEC, Habibie H, Borghuis T, Teitsma GJ, Schuliga M, Melgert BN, et al., 'Regulation of Cellular Senescence Is Independent from Profibrotic Fibroblast-Deposited ECM', CELLS, 10 (2021) [C1]
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2021 |
Schuliga M, Kanwal A, Read J, Blokland KEC, Burgess JK, Prele CM, et al., 'A cGAS-dependent response links DNA damage and senescence in alveolar epithelial cells: a potential drug target in IPF', AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 321 L859-L871 (2021) [C1]
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2021 |
Schuliga M, Read J, Knight DA, 'Ageing mechanisms that contribute to tissue remodeling in lung disease', AGEING RESEARCH REVIEWS, 70 (2021) [C1]
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2021 |
Waters DW, Schuliga M, Pathinayake PS, Wei L, Tan H-Y, Blokland KEC, et al., 'A Senescence Bystander Effect in Human Lung Fibroblasts', BIOMEDICINES, 9 (2021) [C1]
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2020 |
Schuliga M, Read J, Blokland KEC, Waters DW, Burgess J, Prele C, et al., 'Self DNA perpetuates IPF lung fibroblast senescence in a cGAS-dependent manner', CLINICAL SCIENCE, 134 889-905 (2020) [C1]
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2020 |
Blokland KEC, Waters DW, Schuliga M, Read J, Pouwels SD, Grainge CL, et al., 'Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing', PHARMACEUTICS, 12 (2020) [C1]
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2020 |
Knight DA, Grainge CL, Stick SM, Kicic A, Schuliga M, 'Epithelial Mesenchymal Transition in Respiratory Disease: Fact or Fiction', Chest, 157 1591-1596 (2020) [C1]
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2020 |
Blokland KEC, Pouwels SD, Schuliga M, Knight DA, Burgess JK, 'Regulation of cellular senescence by extracellular matrix during chronic fibrotic diseases', Clinical Science, 134 2681-2706 (2020) [C1]
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2019 |
Murtha L, Morten M, Schuliga M, Mabotuwana N, Hardy S, Waters D, et al., 'The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis', Aging and Disease, 10 419-428 (2019) [C1]
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2019 |
Waters DW, Blokland KEC, Pathinayake PS, Wei L, Schuliga M, Jaffar J, et al., 'STAT3 Regulates the Onset of Oxidant-induced Senescence in Lung Fibroblasts.', Am J Respir Cell Mol Biol, 61 61-73 (2019) [C1]
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2018 |
Waters DW, Blokland KEC, Pathinayake PS, Burgess JK, Mutsaers SE, Prele CM, et al., 'Fibroblast senescence in the pathology of idiopathic pulmonary fibrosis', American Journal of Physiology - Lung Cellular and Molecular Physiology, 315 L162-L172 (2018) [C1] Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneu monia of unknown cause with a median survival of only three years. Little is known about the mechanism... [more] Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneu monia of unknown cause with a median survival of only three years. Little is known about the mechanisms that precede the excessive collagen deposition seen in IPF, but cellular senescence has been strongly implicated in disease pathology. Senescence is a state of irreversible cell-cycle arrest accompanied by an abnormal secretory profile and is thought to play a critical role in both development and wound repair. Normally, once a senescent cell has contributed to wound repair, it is promptly removed from the environment via infiltrating immune cells. However, if immune clearance fails, the persistence of senescent cells is thought to drive disease pathology through their altered secretory profile. One of the major cell types involved in wound healing is fibroblasts, and senescent fibroblasts have been identified in the lungs of patients with IPF and in fibroblast cultures from IPF lungs. The question of what is driving abnormally high numbers of fibroblasts into senescence remains unanswered. The transcription factor signal transducer and activator of transcription 3 (STAT3) plays a role in a myriad of processes, including cell-cycle progression, gene transcription, as well as mitochondrial respiration, all of which are dysregulated during senescence. Activation of STAT3 has previously been shown to correlate with IPF progression and therefore is a potential molecular target to modify early-stage senescence and restore normal fibroblast function. This review summarizes what is presently known about fibroblast senescence in IPF and how STAT3 may contribute to this phenotype.
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2018 |
Schuliga M, Pechkovsky DV, Read J, Waters DW, Blokland KEC, Reid AT, et al., 'Mitochondrial dysfunction contributes to the senescent phenotype of IPF lung fibroblasts', JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 22 5847-5861 (2018) [C1]
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2018 |
Schuliga M, Grainge C, Westall G, Knight D, 'The fibrogenic actions of the coagulant and plasminogen activation systems in pulmonary fibrosis', International Journal of Biochemistry and Cell Biology, 97 108-117 (2018) [C1] Fibrosis causes irreversible damage to lung structure and function in restrictive lung diseases such as idiopathic pulmonary fibrosis (IPF). Extravascular coagulation involving fi... [more] Fibrosis causes irreversible damage to lung structure and function in restrictive lung diseases such as idiopathic pulmonary fibrosis (IPF). Extravascular coagulation involving fibrin formation in the intra-alveolar compartment is postulated to have a pivotal role in the development of pulmonary fibrosis, serving as a provisional matrix for migrating fibroblasts. Furthermore, proteases of the coagulation and plasminogen activation (plasminergic) systems that form and breakdown fibrin respectively directly contribute to pulmonary fibrosis. The coagulants, thrombin and factor Xa (FXa) evoke fibrogenic effects via cleavage of the N-terminus of protease-activated receptors (PARs). Whilst the formation and activity of plasmin, the principle plasminergic mediator is suppressed in the airspaces of patients with IPF, localized increases are likely to occur in the lung interstitium. Plasmin-evoked proteolytic activation of factor XII (FXII), matrix metalloproteases (MMPs) and latent, matrix-bound growth factors such as epidermal growth factor (EGF) indirectly implicate plasmin in pulmonary fibrosis. Another plasminergic protease, urokinase plasminogen activator (uPA) is associated with regions of fibrosis in the remodelled lung of IPF patients and elicits fibrogenic activity via binding its receptor (uPAR). Plasminogen activator inhibitor-1 (PAI-1) formed in the injured alveolar epithelium also contributes to pulmonary fibrosis in a manner that involves vitronectin binding. This review describes the mechanisms by which components of the two systems primarily involved in fibrin homeostasis contribute to interstitial fibrosis, with a particular focus on IPF. Selectively targeting the receptor-mediated mechanisms of coagulant and plasminergic proteases may limit pulmonary fibrosis, without the bleeding complications associated with conventional anti-coagulant and thrombolytic therapies.
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2017 |
Murtha LA, Schuliga MJ, Mabotuwana NS, Hardy SA, Waters DW, Burgess JK, et al., 'The processes and mechanisms of cardiac and pulmonary fibrosis', Frontiers in Physiology, 8 1-15 (2017) [C1]
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2017 |
Schuliga M, Jaffar J, Harris T, Knight DA, Westall G, Stewart AG, 'The fibrogenic actions of lung fibroblast-derived urokinase: A potential drug target in IPF', Scientific Reports, 7 1-11 (2017) [C1]
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2017 |
Schuliga M, Jaffar J, Berhan A, Langenbach S, Harris T, Waters D, et al., 'Annexin A2 contributes to lung injury and fibrosis by augmenting factor Xa fibrogenic activity', American Journal of Physiology - Lung Cellular and Molecular Physiology, 312 L772-L782 (2017) [C1] In lung injury and disease, including idiopathic pulmonary fibrosis (IPF), extravascular factor X is converted into factor Xa (FXa), a coagulant protease with fibrogenic actions. ... [more] In lung injury and disease, including idiopathic pulmonary fibrosis (IPF), extravascular factor X is converted into factor Xa (FXa), a coagulant protease with fibrogenic actions. Extracellular annexin A2 binds to FXa, augmenting activation of the protease-activated receptor-1 (PAR-1). In this study, the contribution of annexin A2 in lung injury and fibrosis was investigated. Annexin A2 immunoreactivity was observed in regions of fibrosis, including those associated with fibroblasts in lung tissue of IPF patients. Furthermore, annexin A2 was detected in the conditioned media and an EGTA membrane wash of human lung fibroblast (LF) cultures. Incubation with human plasma (5% vol/vol) or purified FXa (15¿50 nM) evoked fibrogenic responses in LF cultures, with FXa increasing interleukin-6 (IL-6) production and cell number by 270 and 46%, respectively (P < 0.05, n = 5¿8). The fibrogenic actions of plasma or FXa were attenuated by the selective FXa inhibitor apixaban (10 µM, or antibodies raised against annexin A2 or PAR-1 (2 µg/ml). FXastimulated LFs from IPF patients (n = 6) produced twice as much IL-6 as controls (n = 10) (P < 0.05), corresponding with increased levels of extracellular annexin A2. Annexin A2 gene deletion in mice reduced bleomycin-induced increases in bronchoalveolar lavage fluid (BALF) IL-6 levels and cell number (*P < 0.05; n = 4¿12). Lung fibrogenic gene expression and dry weight were reduced by annexin A2 gene deletion, but lung levels of collagen were not. Our data suggest that annexin A2 contributes to lung injury and fibrotic disease by mediating the fibrogenic actions of FXa. Extracellular annexin A2 is a potential target for the treatment of IPF.
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2016 |
Schuliga M, Royce SG, Langenbach S, Berhan A, Harris T, Keenan CR, Stewart AG, 'The coagulant factor Xa induces protease-activated receptor-1 and annexin A2-dependent airway smooth muscle cytokine production and cell proliferation', American Journal of Respiratory Cell and Molecular Biology, 54 200-209 (2016) [C1] During asthma exacerbation, plasma circulating coagulant factor X (FX) enters the inflamed airways and is activated (FXa). FXa may have an important role in asthma, being involved... [more] During asthma exacerbation, plasma circulating coagulant factor X (FX) enters the inflamed airways and is activated (FXa). FXa may have an important role in asthma, being involved in thrombin activation and an agonist of protease-activated receptor-1 (PAR-1). Extracellular annexin A2 and integrins are also implicated in PAR-1 signaling. In this study, the potential role of PAR-1 in mediating the effects of FXa on human airway smooth muscle (ASM) cell cytokine production and proliferation was investigated. FXa (5-50 nM), but not FX, stimulated increases in ASM IL-6 production and cell number after 24- and 48-hour incubation, respectively (P < 0.05; n = 5). FXa (15 nM) also stimulated increases in the levels of mRNA for cytokines (IL-6), cell cycle-related protein (cyclin D1), and proremodeling proteins (FGF-2, PDGF-B, CTGF, SM22, and P AI-1) after 3-hour incubation (P < 0.05; n = 4). The actions of FXa were insensitive to inhibition by hirudin (1 U/ml), a selective thrombin inhibitor, but were attenuated by SCH79797 (100 nM), a PAR-1 antagonist, or Cpd 22 (1 µM), an inhibitor of integrin-linked kinase. The selective targeting of PAR-1, annexin A2, or ß 1-integrin by small interfering RNA and/or by functional blocking antibodies also attenuated FXa-evoked responses. In contrast, the targeting of annexin A2 did not inhibit thrombin-stimulated ASM function. In airway biopsies of patients with asthma, FXa and annexin A2 were detected in the ASM bundle by immunohistochemistry. These findings establish FXa as a potentially important asthma mediator, stimulating ASM function through actions requiring PAR-1 and annexin A2 and involving integrin coactivation.
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2014 |
Alkhouri H, Poppinga WJ, Tania NP, Ammit A, Schuliga M, 'Regulation of pulmonary inflammation by mesenchymal cells', Pulmonary Pharmacology and Therapeutics, 29 156e165-156e165 (2014) Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonar... [more] Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue remodelling, but also have an important role in pulmonary inflammation. This review will describe the immunomodulatory functions of pulmonary mesenchymal cells, such as airway smooth muscle (ASM) cells and lung fibroblasts, in chronic respiratory disease. An important theme of the review is that pulmonary mesenchymal cells not only respond to inflammatory mediators, but also produce their own mediators, whether pro-inflammatory or pro-resolving, which influence the quantity and quality of the lung immune response. The notion that defective pro-inflammatory or pro-resolving signalling in these cells potentially contributes to disease progression is also discussed. Finally, the concept of specifically targeting pulmonary mesenchymal cell immunomodulatory function to improve therapeutic control of chronic respiratory disease is considered.
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2013 |
Stewart AG, Xia YC, Harris T, Royce S, Hamilton JA, Schuliga M, 'Plasminogen-stimulated airway smooth muscle cell proliferation is mediated by urokinase and annexin A2, involving plasmin-activated cell signalling', British Journal of Pharmacology, 170 1421-1435 (2013) [C1] Background and Purpose The conversion of plasminogen into plasmin by interstitial urokinase plasminogen activator (uPA) is potentially important in asthma pathophysiology. In this... [more] Background and Purpose The conversion of plasminogen into plasmin by interstitial urokinase plasminogen activator (uPA) is potentially important in asthma pathophysiology. In this study, the effect of uPA-mediated plasminogen activation on airway smooth muscle (ASM) cell proliferation was investigated. Experimental Approach Human ASM cells were incubated with plasminogen (0.5-50 µg·mL-1) or plasmin (0.5-50 mU·mL-1) in the presence of pharmacological inhibitors, including UK122, an inhibitor of uPA. Proliferation was assessed by increases in cell number or MTT reduction after 48 h incubation with plasmin(ogen), and by earlier increases in [ 3H]-thymidine incorporation and cyclin D1 expression. Key Results Plasminogen (5 µg·mL-1)-stimulated increases in cell proliferation were attenuated by UK122 (10 µM) or by transfection with uPA gene-specific siRNA. Exogenous plasmin (5 mU·mL-1) also stimulated increases in cell proliferation. Inhibition of plasmin-stimulated ERK1/2 or PI3K/Akt signalling attenuated plasmin-stimulated increases in ASM proliferation. Furthermore, pharmacological inhibition of cell signalling mediated by the EGF receptor, a receptor trans-activated by plasmin, also reduced plasmin(ogen)-stimulated cell proliferation. Knock down of annexin A2, which has dual roles in both plasminogen activation and plasmin-signal transduction, also attenuated ASM cell proliferation following incubation with either plasminogen or plasmin. Conclusions and Implications Plasminogen stimulates ASM cell proliferation in a manner mediated by uPA and involving multiple signalling pathways downstream of plasmin. Targeting mediators of plasminogen-evoked ASM responses, such as uPA or annexin A2, may be useful in the treatment of asthma. © 2013 The British Pharmacological Society.
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2013 |
Schuliga M, Langenbach S, Xia YC, Qin C, Mok JSL, Harris T, et al., 'Plasminogen-Stimulated Inflammatory Cytokine Production by Airway Smooth Muscle Cells Is Regulated by Annexin A2', AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 49 751-758 (2013) [C1]
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2013 |
Schuliga M, Langenbach S, Xia YC, Qin C, Mok JSL, Harris T, et al., 'Plasminogen-stimulated inflammatory cytokine production by airway smooth muscle cells is regulated by annexin A2', American Journal of Respiratory Cell and Molecular Biology, 49 751-758 (2013) Plasminogen has a role in airway inflammation. Airway smooth muscle(ASM) cells cleave plasminogen into plasmin, a protease with proinflammatory activity. In this study, the effect... [more] Plasminogen has a role in airway inflammation. Airway smooth muscle(ASM) cells cleave plasminogen into plasmin, a protease with proinflammatory activity. In this study, the effect of plasminogen on cytokine production by human ASM cells was investigated in vitro. Levels of IL-6 and IL-8 in the medium of ASM cells were increased byincubation with plasminogen (5-50 µg/ml) for 24 hours (P,0.05; n = 6-9), corresponding to changes in the levels of cytokine mRNA at 4 hours. The effects of plasminogen were attenuated by a2- antiplasmin (1 mg/ml), a plasmin inhibitor (P < 0.05; n = 6-12). Exogenous plasmin (5-15 mU/ml) also stimulated cytokine production (P < 0.05; n = 6-8) in a manner sensitive to serine-protease inhibition by aprotinin (10 KIU/ml). Plasminogen-stimulated cytokine production was increased in cells pretreated with basic fibroblast growth factor (300 pM) in a manner associated with increases in urokinase plasminogen activator expression and plasmin formation. The knockdown of annexin A2, a component of the putative plasminogen receptor comprised of annexin A2 and S100A10, attenuated plasminogen conversion into plasmin and plasmin-stimulated cytokine production byASMcells. Moreover, a role for annexin A2 in airway inflammation was demonstrated in annexin A2-/- mice in which antigen-induced increases in inflammatory cell number and IL-6 levels in the bronchoalveolar lavage fluid were reduced (P < 0.01; n = 10-14). In conclusion, plasminogen stimulates ASM cytokine production in a manner regulated by annexin A2. Our study shows for the first time that targeting annexin A2-mediated signaling may provide a novel therapeutic approach to the treatment of airway inflammation in diseases such as chronic asthma. Copyright © 2013 by the American Thoracic Society.
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2013 |
Schuliga M, Westall G, Xia Y, Stewart AG, 'The plasminogen activation system: New targets in lung inflammation and remodeling', Current Opinion in Pharmacology, 13 386-393 (2013) [C1] The plasminogen activation system (PAS) and the plasmin it forms have dual roles in chronic respiratory diseases including asthma, chronic obstructive pulmonary disease and inters... [more] The plasminogen activation system (PAS) and the plasmin it forms have dual roles in chronic respiratory diseases including asthma, chronic obstructive pulmonary disease and interstitial lung disease. Whilst plasmin-mediated airspace fibrinolysis is beneficial, interstitial plasmin contributes to lung dysfunction because of its pro-inflammatory and tissue remodeling activities. Recent studies highlight the potential of fibrinolytic agents, including small molecule inhibitors of plasminogen activator inhibitor-1 (PAI-1), as treatments for chronic respiratory disease. Current data also suggest that interstitial urokinase plasminogen activator is an important mediator of lung inflammation and remodeling. However, further preclinical characterization of uPA as a drug target for lung disease is required. Here we review the concept of selectively targeting the contributions of PAS to treat chronic respiratory disease. © 2013 Elsevier Ltd. All rights reserved.
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Conference (48 outputs)
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2020 |
Kanwal A, Grainge C, Knight DA, Schuliga M, Bartlett NW, 'The Fibrogenic Actions of IL-25 and Its Potential Role in Idiopathic Pulmonary Fibrosis (IPF)', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, ELECTR NETWORK (2020)
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2019 |
Blokland K, Waters D, Schuliga M, Pouwels S, Grainge C, Mutsaers S, et al., 'Alveolar epithelial wound repair is delayed by scenescent lung fibroblasts in IPF', EUROPEAN RESPIRATORY JOURNAL, Madrid, SPAIN (2019)
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2019 |
Schuliga M, Jaffar J, Westall G, Blokland K, Waters D, Burgess J, et al., 'CGAS IS A PIVOTAL MEDIATOR OF IPF LUNG FIBROBLAST SENESCENCE', RESPIROLOGY (2019)
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2014 | Schuliga M, Harris T, Royce S, Stewart A, 'The coagulant factor Xa induces PAR-1 and annexin A2-dependent airway smooth muscle cytokine production and cell proliferation', EUROPEAN RESPIRATORY JOURNAL (2014) | ||||||||||
2014 | Meurs H, Minovic I, Harris T, Xia YC, Schuliga M, Gosens R, et al., 'Potential Role For Chondrocytes In Airway Remodeling', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2014) | ||||||||||
2014 |
Schuliga M, Xia Y, Langenbach S, Harris T, Stewart AG, 'Extracellular Annexin A2 Mediates Lung Fibroblast Cytokine Production And Proliferation: A Potential Role In Pulmonary Fibrosis', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2014)
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2014 | Schuliga M, Langenbach S, Xia Y, Harris T, Stewart A, 'EXTRACELLULAR ANNEXIN A2 MEDIATES INFLAMMATORY AND FIBRO-PROLIFERATIVE RESPONSES IN MODELS OF PULMONARY FIBROSIS', RESPIROLOGY (2014) | ||||||||||
2013 | Keenan CR, Salem S, Harris T, Schuliga M, Stewart AG, 'Transforming Growth Factor-beta Induces Glucocorticoid Resistance In Human Bronchial Epithelial Cells', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2013) | ||||||||||
2013 | Schuliga M, Harris T, Xia YC, Wang Z, Zhang X, Srinivason V, et al., 'Fgf-2 Modulates Human Airway Smooth Muscle Contractile Protein Expression And Cell Stiffness In A Reversible, Smad-Independent Manner', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2013) | ||||||||||
2013 | Schuliga M, Xia YC, Harris T, Stewart AG, 'Plasminogen-Stimulated Airway Smooth Muscle Cell Proliferation Is Mediated By Urokinase And Involves Plasmin-Activated Cell Signaling', AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2013) | ||||||||||
2013 |
Schuliga M, Javeed A, Harris T, Xia Y, Qin C, Wang Z, et al., 'Transforming growth factor-ß-Induced differentiation of airway smooth muscle cells is inhibited by fibroblast growth factor-2', American Journal of Respiratory Cell and Molecular Biology (2013) [C1] In asthma, basic fibroblast growth factor (FGF-2) plays an important (patho)physiological role. This study examines the effects of FGF-2 on the transforming growth factor-b (TGF-b... [more] In asthma, basic fibroblast growth factor (FGF-2) plays an important (patho)physiological role. This study examines the effects of FGF-2 on the transforming growth factor-b (TGF-b)-stimulated differentiation of airway smooth muscle (ASM) cells in vitro. The differentiation of humanASMcells after incubation with TGF-b(100 pM)and/ or FGF-2 (300 pM) for 48 hours was assessed by increases in contractile protein expression, actin-cytoskeleton reorganization, enhancements in cell stiffness, and collagen remodeling. FGF-2 inhibited TGF-ß-stimulated increases in transgelin (SM22) and calponin gene expression (n = 15, P < 0.01) in an extracellular signal-regulated kinase 1/2 (ERK1/2) signal transduction-dependent manner. The abundance of ordered a-smooth muscle actin (a-SMA) filaments formed in the presence of TGF-b were also reduced by FGF-2, as was the ratio of F-actin to G-actin (n = 8, P < 0.01). Furthermore, FGF-2 attenuated TGF-ß-stimulated increases in ASM cell stiffness andtheASM-mediatedcontraction of lattices,composed of collagen fibrils (n = 5, P < 0.01). However, the TGF-ß-stimulated production of IL-6 was not influenced by FGF-2 (n=4, P.>.05), suggesting that FGF-2 antagonism is selective for the regulation of ASM cell contractile protein expression, organization, and function. Another mitogen, thrombin (0.3 U ml21), exerted no effect on TGF-ß-regulated contractile protein expression (n=8, P.>.05),a-SMA organization, or the ratio of F-actin to G-actin (n=4, P.>.05), suggesting that the inhibitory effect of FGF-2 is dissociated from its mitogenic actions. The addition of FGF-2, 24 hours after TGF-b treatment, still reduced contractile protein expression, even when the TGF-ß-receptor kinase inhibitor, SB431542 (10 mM), was added 1 hour before FGF-2. Weconclude that the ASM cell differentiation promoted by TGF-b is antagonized by FGF-2. A better understanding of the mechanism of action for FGF-2 is necessary to develop a strategy for therapeutic exploitation in the treatment of asthma. Copyright © 2013 by the American Thoracic Society.
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2013 | Schuliga M, Harris T, Xia Y, Wang Z, Zhang X, Lee P, Stewart A, 'FGF-2 modulates human airway smooth muscle contractile protein expression and cell stiffness', EUROPEAN RESPIRATORY JOURNAL (2013) | ||||||||||
2013 |
Keenan C, Lopez-Campos G, Salem S, Harris T, Schuliga M, Johnstone C, Stewart A, 'RNA-seq analysis of transforming growth factor-beta-induced glucocorticoid resistance in human bronchial epithelial cells', EUROPEAN RESPIRATORY JOURNAL (2013)
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2013 |
Keenan CR, Salem S, Harris T, Schuliga M, Stewart AG, 'TRANSFORMING GROWTH FACTOR-beta INDUCES GLUCOCORTICOID RESISTANCE IN HUMAN BRONCHIAL EPITHELIAL CELLS', RESPIROLOGY (2013)
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Show 45 more conferences |
Grants and Funding
Summary
Number of grants | 16 |
---|---|
Total funding | $2,454,794 |
Click on a grant title below to expand the full details for that specific grant.
20241 grants / $18,430
Using a novel lung epithelial cell-fibroblast co-culture model to identify key molecular pathways involved in alveolar epithelial injury and abnormal repair in idiopathic pulmonary fibrosis (IPF)$18,430
Funding body: Hunter New England Local Health District
Funding body | Hunter New England Local Health District |
---|---|
Project Team | Mrs Jane Read, Conjoint Associate Professor Christopher Grainge, Doctor Michael Schuliga |
Scheme | John Hunter Hospital Charitable Trust Grant |
Role | Investigator |
Funding Start | 2024 |
Funding Finish | 2024 |
GNo | G2400662 |
Type Of Funding | C2400 – Aust StateTerritoryLocal – Other |
Category | 2400 |
UON | Y |
20232 grants / $607,805
The roles of replicative senescence and telomere dysfunction in the heightened injury and disrepair responses of alveolar epithelial cells from patients with pulmonary fibrosis$597,680
Funding body: Boehringer Ingelheim International GmbH
Funding body | Boehringer Ingelheim International GmbH |
---|---|
Project Team | Doctor Michael Schuliga, Conjoint Associate Professor Christopher Grainge, Professor Darryl Knight |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2023 |
Funding Finish | 2025 |
GNo | G2301207 |
Type Of Funding | C3400 – International For Profit |
Category | 3400 |
UON | Y |
Idiopathic Pulmonary Fibrosis research$10,125
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Doctor Michael Schuliga, Conjoint Associate Professor Christopher Grainge, Mrs Jane Read |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2023 |
Funding Finish | 2023 |
GNo | G2300770 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
20221 grants / $10,484
Urokinase receptor (uPAR) signalling de-sensitizes lung fibroblasts to apoptosis in idiopathic pulmonary fibrosis (IPF)$10,484
Funding body: Hunter New England Local Health District
Funding body | Hunter New England Local Health District |
---|---|
Project Team | Doctor Michael Schuliga, Dr Koliame Tong |
Scheme | John Hunter Hospital Charitable Trust Grant |
Role | Lead |
Funding Start | 2022 |
Funding Finish | 2022 |
GNo | G2200189 |
Type Of Funding | C2400 – Aust StateTerritoryLocal – Other |
Category | 2400 |
UON | Y |
20212 grants / $508,659
To Support The Potential Identification Of New Therapeutic Targets In IPF/PF-ILD Patient-Derived Airway And Alveolar Epithelial Cell Cultures$469,688
Funding body: Boehringer Ingelheim International GmbH
Funding body | Boehringer Ingelheim International GmbH |
---|---|
Project Team | Doctor Michael Schuliga, Professor Darryl Knight |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2021 |
Funding Finish | 2023 |
GNo | G2100417 |
Type Of Funding | C3400 – International For Profit |
Category | 3400 |
UON | Y |
HMRI Researcher Salary Bridging Funds$38,971
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Doctor Michael Schuliga |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2021 |
Funding Finish | 2022 |
GNo | G2100292 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
20191 grants / $76,216
Research equipment grant$76,216
Funding body: Faculty of Health and Medicine Research Equipment Grant Round
Funding body | Faculty of Health and Medicine Research Equipment Grant Round |
---|---|
Project Team | Dr Michael Schuliga |
Scheme | Faculty of Health and Medicine Research Equipment Grant Round |
Role | Lead |
Funding Start | 2019 |
Funding Finish | 2019 |
GNo | |
Type Of Funding | Internal |
Category | INTE |
UON | N |
20181 grants / $5,000
Annexin A2 in IPF and potential as novel therapeutic target$5,000
Funding body: Lung Foundation Australia
Funding body | Lung Foundation Australia |
---|---|
Project Team | Doctor Michael Schuliga, Professor Darryl Knight, Conjoint Associate Professor Christopher Grainge |
Scheme | Lizotte Family Research Award for Interstitial Pulmonary Fibrosis Research |
Role | Lead |
Funding Start | 2018 |
Funding Finish | 2018 |
GNo | G1801058 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
20173 grants / $45,000
Mechano-transduction signaling complexes of urokinase and its receptor in lung fibrosis: A potential target for idiopathic pulmonary fibrosis (IPF)$20,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Doctor Michael Schuliga, Conjoint Associate Professor Christopher Grainge, Professor Darryl Knight |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2017 |
GNo | G1700697 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
Mechano-transduction signalling complexes of urokinase and it receptor in lung fibrosis: A potential target for idiopathic pulmonary fibrosis (IPF)$20,000
Funding body: John Hunter Charitable Trust Grant
Funding body | John Hunter Charitable Trust Grant |
---|---|
Project Team | Dr Michael Schuliga (CIA), A/Prof Chris Grainge (CIB) & Prof Darryl Knight (CIC) |
Scheme | John Hunter Charitable Trust Grant |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2017 |
GNo | |
Type Of Funding | Grant - Aust Non Government |
Category | 3AFG |
UON | N |
Annexin A2 in IPF and potential as novel therapeutic target $5,000
Funding body: Lung Foundation Australia
Funding body | Lung Foundation Australia |
---|---|
Scheme | Research Award |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2018 |
GNo | |
Type Of Funding | Grant - Aust Non Government |
Category | 3AFG |
UON | N |
20151 grants / $43,700
Effect of biomechanical strain on lung fibroblast function$43,700
Funding body: Faculty of Medicine, Dental and Health Sciences
Funding body | Faculty of Medicine, Dental and Health Sciences |
---|---|
Project Team | Dr Michael Schuliga |
Scheme | Research Grant Support Scheme |
Role | Lead |
Funding Start | 2015 |
Funding Finish | 2016 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
20131 grants / $536,500
Airway smooth muscle and fixed airway obstruction: strategies for softening muscle $536,500
APP1045372
To investigate the inhibitory effect of FGF-2 on ASM cell hypertrophy and cell stiffness, and to test the validity of using FGF-2 mechanism selective-analogues in the treatment of airway obstruction in asthma.Funding body: National Health & Medical Research Council of Australia (NH&MRC)
Funding body | National Health & Medical Research Council of Australia (NH&MRC) |
---|---|
Project Team | Pfor Alastair Stewart (CIA), Dr Michael Schuliga (CIB), Prof Peter Lee (CIC) and Dr Xuehua Zhang (CID) |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2013 |
Funding Finish | 2015 |
GNo | |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | N |
20121 grants / $538,000
Urokinase is a key mediator of airway inflammation and tissue remodelling in asthma$538,000
APP1022048
To investigate the role of urokinase (uPA) in airway inflammation and tissue remodelling, and determine whether uPA is a therapeutic target for asthma.
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Dr Michael Schuliga (CIA), Prof Alastair Stewart (CIB) and Dr. Lilian Soon (CIC) |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2012 |
Funding Finish | 2014 |
GNo | |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | N |
20092 grants / $65,000
Fibrinolysis in acute lung injury: validation of annexin A2 as a novel drug target$40,000
Funding body: CASS Foundation
Funding body | CASS Foundation |
---|---|
Project Team | Prof Alastair Stewart and Dr Michael Schuliga |
Scheme | Scientific Grants |
Role | Investigator |
Funding Start | 2009 |
Funding Finish | 2009 |
GNo | |
Type Of Funding | Aust Competitive - Non Commonwealth |
Category | 1NS |
UON | N |
Non-fibrinolytic roles for plasmin in asthmatic airways remodelling$25,000
Funding body: Asthma Foundation of Victoria
Funding body | Asthma Foundation of Victoria |
---|---|
Project Team | Dr Michael Schuliga |
Scheme | Helen Macpherson Smith Trust Award |
Role | Lead |
Funding Start | 2009 |
Funding Finish | 2009 |
GNo | |
Type Of Funding | Aust Competitive - Non Commonwealth |
Category | 1NS |
UON | N |
Research Supervision
Number of supervisions
Current Supervision
Commenced | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2022 | PhD | The Role Of Epithelial Senescence In Lung Injury And Fibrosis | PhD (Medical Biochemistry), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2021 | PhD | Targeting Mitochondrial ROS in Airway Epithelial Cells to Prevent Virus Induced Disease in Asthma and COPD | PhD (Pharmacy), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2017 | PhD | An Investigation of Regional Heterogeneity of the Pulmonary Microenvironment in Idiopathic Pulmonary Fibrosis | PhD (Medicine), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2014 | Honours | The role of coagulant proteases in chronic lung disease | Pharmacology, The University of Melbourne | Co-Supervisor |
Past Supervision
Year | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2023 | PhD | The Fibrogenic Actions of IL-25 in Idiopathic Pulmonary Fibrosis (IPF) | PhD (Immunology & Microbiol), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2021 | PhD | The ECM as a Driver of Fibroblast Senescence and Disrupted Epithelial Repair in IPF | PhD (Immunology & Microbiol), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2019 | PhD | Fibroblast Senescence as a Driver of Idiopathic Pulmonary Fibrosis | PhD (Immunology & Microbiol), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2019 | PhD | Stiffness: a master regulator of fibrogenesis? | Medical Science, The University of Melbourne | Co-Supervisor |
2013 | PhD | Transforming growth factor-β impairs glucocorticoid activity in airway epithelial cells | Pharmacology, The University of Melbourne | Co-Supervisor |
Dr Michael Schuliga
Position
Postdoctoral Research Associate
Knight Group
School of Biomedical Sciences and Pharmacy
College of Health, Medicine and Wellbeing