Stewart Laboratory: Mechanopharmacology
|Professor Alastair Stewartfirstname.lastname@example.org||+61 3 8344 5675||View page|
About Professor Alastair Stewart
Professor Alastair Stewart has extensive experience in the field of respiratory and inflammation research. He has published over 200 papers, has had three patents proceed to grant and has served on numerous peer review committees for NHMRC and the scientific advisory boards of several Australian Medical Research Institutes. Prof Stewart currently Chairs the Therapeutic Technologies Research Initiative (TTRI), The University of Melbourne; Co-Director, Lung Health Research Centre (LHRC), The University of Melbourne; Professor of Pharmacology, School of Biomedical Sciences, The University of Melbourne; and Director of the ARC-Industry Transformation Training Centre (ARC-ITTC) for Personalised Therapeutics Technologies. He is Vice President of the Asia Pacific Federation of Pharmacologists and a member of the Nominating and Programming Committees of the Respiratory Structure Function assembly of the American Thoracic Society. His editorial roles include Chief Editor of the Translational Pharmacology section of Frontiers in Pharmacology and Senior Associate Editor of the American Society for Mechanical Engineering Journal (ASME), Journal of Engineering and Science in Medical Diagnostics and Therapy. Prof Stewart is developing and applying the concept of mechanopharmacology in drug discovery and ultra-high content screening.
The laboratory conducts, translational and contract research and consultancies.
The Mechanopharmacology Lab is investigating inflammation and fibrosis mechanisms using novel bioassays for drug discovery and characterisation. A range of systems pharmacology-based analytical approaches are applied using transcriptomic and proteomic data from well-qualified clinical and experimental specimens. The lab has extensive links to Biomedical Engineering, Chemistry and Physics and strong connections to TTRI, LHRC and ARC-ITTC (Personalised Therapeutic Technologies).
Current projects include:
- Glucocorticoid sensitivity in structural cells of the airway using Air Liquid Interface Culture.
- Regulation of mesenchymal cell growth, differentiation and function.
- Anti-remodelling activity of currently used and potential anti-asthma agents.
- Impact of extracellular matrix components on the efficacy of anti-remodelling agents.
- Role of circadian mechanisms in inflammation and tissue remodelling.
Project details may be found on the individual research project pages.
The Mechanopharmacology Lab offers opportunities for placement for BScHons, Masters and PhD candidates and provides a supportive interdisciplinary environment, staffed with highly experienced scientists able to foster translational research goals. Inquiries are welcome.
Dr Connie Xia, NHMRC Peter Doherty Research Fellow
Dr Philippe LaChapelle, Visiting Respiratory Fellow
Ms Shenna Langenbach, Senior Research Assistant
Ms Trudi Harris, Senior Research Assistant
Ms Meina Li, PhD Student
Ms Danica Radojicic, PhD Student
Mr Asres Mitke, PhD Student
Mr Fernando Guzman, PhD Student
Ms Asmaa Radwan, PhD Student
Ms Qianyu Chen, PhD Student
Mr Yanqi Wu, PhD Student
Ms Yan Tu, PhD Student
Ms Aakriti Sharma, BSc Hons student
Staff and Students
Dr Maria Bellesis
Dr Susan Northfield
ARC-ITTC (Personalised Therapeutic Technologies)
Final PhD Orations were recently given by the following students:
Meina received a Bachelor of Pharmacy degree in 2010 from Shandong University (China) and a Master’s degree in Pharmaceutical analysis in 2013 from Peking University (China). After graduating from Peking University, Meina joined the Mechanopharmacology laboratory in 2013, with the support of a Chancellor’s scholarship that was established to strengthen the connection between Melbourne University and Peking University. Meina’s major research interest has been trying to understand the signalling of transforming growth factor beta-induced steroid resistance and identifying drug targets that will spare essential growth and immunoregulatory effects of transforming growth factor beta (thereby facilitating the development of safe modulators of its profoundly significant compromise to steroid activity). In addition to scientific work, Meina enjoys traveling, photography and writing and she would like to share with people how wonderful Australia and the world are using her images and words.
Danica received her Master’s degree in Pharmacy in 2013 from the University of Belgrade (Serbia). She was awarded with two Melbourne international scholarships to join the Mechanopharmacology laboratory, starting her PhD project under Alastair Stewart’s supervision in March 2014. Her research interests include the pharmacology of glucocorticoids and the mechanisms of their actions and insensitivity in the airway epithelium, particularly in asthma. As part of her PhD, she investigated the role of the specific transcriptional repressor PLZF in mediating glucocorticoid effects in the airway epithelium. She also explored the effect of the physiological glucocorticoid, cortisol on the actions of synthetic, therapeutically used glucocorticoids in the airway epithelium, using both human in vitro models, including the air-liquid interface cultures of primary human bronchial epithelial cells and in vivo animal models. Apart from her love for research and science, Danica is also a professional singer and songwriter. She competed in Eurovision, representing Serbia in 2011.
The University of Melbourne
Dr Jon Mangum, Department of Pharmacology & Therapeutics
Dr Graham Mackay, Department of Pharmacology & Therapeutics
Professor Peter Lee, Biomedical Engineering
Dr Sarah Londrigan, Microbiology and Immunology, Peter Doherty institute
Dr David Simpson, School of Physics
Professor Lloyd Hollenberg, School of Physics
Professor Spencer Williams, School of Chemistry, The University of Melbourne
Professor Jo Douglass, Clinical immunology and Allergy, The Royal Melbourne Hospital
Associate Professor Glen Westall, AIRMed, The Alfred Hospital
Dr Jin-Ah Park, Harvard TH Chan School of Public Health, USA
Professor Martina Schmidt, University of Groningen, The Netherlands
Dr Michael Schuliga, University Newcastle, NSW
The Laboratory receives funding from the following bodies:
- Asthma Australia
For a full list of publications go to Professor Stewart's ‘Find an Expert’ profile.
- Qin CX, May LT, Li R, Cao N, Rosli S, Deo M, Alexander AE, Horlock D, Bourke JE, Yang YH, Stewart AG, Kaye DM, DuX-J , Sexton PM, Christopoulos A, Gao X-M, Ritchie RH. Small-molecule-biased formyl peptide receptor agonist compound 17b protects against myocardial ischaemia-reperfusion injury in mice. Nature Communications 2017;8:14232 doi: 10.1038/ncomms14232.
- Schuliga M, Jaffar J, Berhan A, Langenbach S, Harris T, Waters D, Lee PVS, Grainge C, Westall G, Knight D, G. Stewart AG. Annexin A2 contributes to lung injury and fibrosis by augmenting factor Xa fibrogenic activity. American Journal of Physiology - Lung Cellular and Molecular Physiology 2017;312 doi: 10.1152/ajplung.00553.2016
- Tu Y, Johnstone CN, Stewart AG. Annexin Al influences in breast cancer: Controversies on contributions to tumour, host an immunoediting processes. Pharmacological Research 2017;119 doi:10.1016/j.phrs.2017.02.011
- Stewart AG. Translational Pharmacology. Frontiers in Pharmacology – Translational Pharmacology. 2017 doi: 10.3389/fphar.2017.00008
- Xia YC, Radwan A, Keenan CR, Langenbach SY, Li M, Radojicic D, Londrigan SL, Gualano RC, Stewart AG. Glucocorticoid insensitivity in virally infected airway epithelial cells is dependent on transforming growth factor- β activity. PLOS Pathogens 2017 doi: 10.1371/journal.ppat.1006138.
- Fietz ER, Keenan CR, Campos GL, Tu Y, Johnstone CN, Harris T, Stewart AG. Glucocorticoid resistance of migration and gene expression in a daughter MDA-MB-231 breast tumour cell line selected for high metastatic potential. Scientific Reports 2017;7:43774 doi:10.1038/srep43774
- Schuliga M, Jaffar J, Berhan A, Westall G, Knight D, Stewart AG.The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF. Scientific Reports 2017;7:41770. doi: 10.1038/srep41770.
- Qiao Y, Tam JKC, Tan SSL, Tai YK, Chin CY, Stewart AG, Ashman L, Sekiguchi K, Langenbach SY, Stelmack G, Halayko AJ, Tran T. Melbourne Epidemiological Study of Childhood Asthma group. CD151, a laminin receptor showing increased expression in asthma, contributes to airway hyperresponsiveness through calcium signaling. J Allergy Clinical Immunology 2017;139(1):82-92.e5 doi: 10.1016/j.jaci.2016.03.029.
- Perret JL, Plush B, Lachapelle P, Hinks TSC, Walter C, Clarke P, Irving L, Brady P, Dharmage SC, Stewart AG. Coal mine workers’ lung disease in the modern era. Respirology 2017;22:662-670.
- Keenan CR, Lew MJ, Stewart AG. Biased signalling from the glucocorticoid receptor: Renewed opportunity for tailoring glucocorticoid activity. Biochemical Pharmacology 2016;112. https://doi.org/10.1016/j.bcp.2016.02.008
- Bidram E, Sulistio A, Amini A, Fu Q, Qiao GG, Stewart AG, Dunstan DE. Fractionation of graphene oxide single nano-sheets in water-glycerol solutions using gradient centrifugation. Carbon 2016;103 doi:10.1016/j.carbon.2016.02.095
- FitzPatrick M, Royce SG, Langenbach S, McQualter J, Reading PC, Wijburg O, Anderson GP, Stewart AG, Bourke J, Bozinovski S. Neonatal pneumococcal colonisation caused by Influenza A infection alters lung function in adult mice. Scientific Reports 2016;6 doi: 10.1038/srep22751
- 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. 2016;54 Doi: 10.1165/rcmb.2014-0419OC.
- Stewart AG, Beart PM. Inflammation: maladies, models, mechanisms and molecules. British Journal of Pharmacology. 2016;173 doi: 10.1111/bph.13389
- Krishnan R, Park JA, Seow CY, Lee PVS, Stewart AG. (2016). Cellular biomechanics in drug screening and evaluation: Mechanopharmacology. Trends in Pharmacological Sciences 2016;37:87-100. doi: 10.1016%2Fj.tips.2015.10.005
- Qin C, Yang YH, May L, Gao X , Stewart AG, Tu Y, Woodman OL, Ritchie RH . Cardioprotective potential of annexin-A1 mimetics in myocardial infarction. Pharmacology and Therapeutics 2015;148 doi: 10.1016/j.pharmthera.2014.11.012.
- Keenan CR, Radojicic D, Li M, Radwan A , Stewart AG. Heterogeneity in mechanisms influencing glucocorticoid sensitivity: The need for a systems biology approach to treatment of glucocorticoid-resistant inflammation. Pharmacology and Therapeutics 2015;150 doi: 10.1016/j.pharmthera.2015.01.006.
- Keenan CR, Schuliga MJ, Stewart AG. Pro-inflammatory mediators increase levels of the noncoding RNA GAS5 in airway smooth muscle and epithelial cells. Canadian Journal of Physiology and Pharmacology 2015;93 doi:10.1139/cjpp-2014-0391
This Research Group doesn't currently have any projects
School Research Themes
For further information about this research, please contact Professor Alastair Stewart