Alastair Stewart laboratory

Research Overview

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 numerous patents proceed to grant and has served on various peer review committees for the NHMRC and the scientific advisory boards of several Australian Medical Research Institutes.  Professor Stewart is Chair of  Pharmacology and Therapeutics at the The University of Melbourne; is Co-Director of the Lung Health Research Centre (LHRC); and is the Director of the national ARC Industry Transformation Training Centre for Personalised Therapeutics Technologies (ARC CPTT). He is CSO and Director of TianLi Biotech, 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 through his capacity as member of the Inaugural Board of the International Microphysiological Systems (MPS) Society, and a steering committee of a CSIRO-initiated review of Non-animal models for preclinical development.

The laboratory conducts, translational and contract research and consultancies.

Laboratory Overview

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 TianLi Biotech, 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.

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.

News from Mechanopharmacology Lab.

Staff

Personnel from Stewart Lab

Researchers

Dr Bryan Gao, Research Fellow
Dr Daniel Tan, Research Fellow
Dr Meina Li, Research Fellow
Dr Qianyu (Helen) Chen, Research Fellow
Dr Tianhong (Tina) Cheng, Research Fellow
Mr Avanka Gunatilaka, PhD Student
Ms Stephanie Zhang, PhD Student
Ms Xiaodan (Emma) Zhang, PhD Student
Ms Jana Zielinski, PhD Student
Ms Yiling (Iris) Yang, PhD Student
Ms Chiao Hwei Lee, PhD Student
Ms Dina Jacob, PhD Student
Mr Song Wang, PhD Student
Ms Shenna Langenbach, Senior Research Assistant

Staff

Dr Delphine Denoyer (ARC CPTT)

Collaborators

The University of Melbourne

  • “Immunoglobulin receptors on airway and lung mesenchymal cells”, Dr Graham McKay, Department of Biochemistry and Pharmacology.
  • “Synthesis and development of novel analogues of resolvin D2”, Prof Mark Rizacassa, School of Chemistry. Science.
  • “Synthesis and characteristic of NCE small molecule anti-fibrotic agents.”, Prof Spencer Williams, School of Chemistry. Science.
  • “Novel biomechanical analyses of airway smooth muscle cell function”, Prof Peter Lee, Mechanical engineering, A/Prof Andrea O’Connor, Dr Daniel Heath, Biomedical Engineering, FEIT.
  • “Control systems and multi-spectral imaging for microfluidics cell culture perfusion and analyses”, Assoc Prof Ranjith Unnithan, Electrical Electronic Engineering, FEIT.
  • “Substituted Graphene oxide nanoparticles as anti-cancer agents”, Prof Dave Dunstan, Chemical and Biomolecular Engineering.
  • “Novel traction force imaging using magnetic fields”, Prof Lloyd Hollenberg, Dr David Simpson, School of Physics.
  • “Flu infection and glucocorticoid sensitivity”, Dr Sarah Londrigan, Peter Doherty Institute, MDHS, UoM.
  • “Flu infection of airway epithelial cells”, Dr Julie McCauley, Prof Lorena Brown, Peter Doherty Institute, MDHS, UoM.
  • “Metabolism in tumour cells”, Prof Gordon Lynch and Dr James Ryall, Department of Physiology.
  • “Microfluidics mechanophenotyping”, Dr Dave Collins, Biomedical engineering, FEIT.
  • “Models for COVID19 infection”, Prof Kanta Subbarao, Peter Doherty Institute, MDHS, UoM.
  • “Lipidomics in steroid resistance and fibrosis”, Prof Gavin Reid, Department of Biochemistry and Pharmacology.
  • “Microfluidic sensors and controls systems”, A/Prof Ranjith Unnithan, Electrical Electronic Engineering, FEIT.

External collaborators

  • “Viral Infection and glucocorticoid sensitivity”, Prof Jo Douglass, Allergy and Clinical Immunology, RMH and Prof Phil Bardin (Monash lung and Sleep).
  • “Interstitial lung disease/Idoiopathic Pulmonary fibrosis: mechanisms and models”, A/Prof Glen Westall, Dr Jade Jaffar (Alfred Health, Monash University). Dr Mike Wilson, Dr Nick Wilson (CSL Ltd).
  • “Laminin and airway smooth muscle phenotype”, Assoc Prof Thai Tran, National University of Singapore.
  • “Novel biomechanical analyses of airway smooth muscle cell function”, Dr Yukiko Matsunaga, University of Tokyo. Prof Toshiro Ohashi, University of Hokkaido, Sapporo, Japan.
  • “LIM kinase, cofilin and steroid responsiveness”, Prof Martina Schmidt, University of Groningen. Groningen, Netherlands.
  • “IL-11 in fibrogenesis”, Prof Reinoud Gosens, University of Groningen. Groningen, Netherlands.
  • “Cellular mechanics and regulation of fibrotic/inflammatory pathways”, Dr Ramaswamy Krishnan, Beth Israel Deaconess medical Centre, Boston.
  • “Annexin A2 in pulmonary fibrosis”, Prof Kai-Feng Xu, Peking Union medical College Hospital, Beijing, China.
  • “Compression and glucocorticoid responses in the epithelium”, Dr Jin-Ah park, TH Chan Harvard School of Public health, Boston.
  • “Sputum analyses in asthma and COPD”, Dr Nick Wilson, CSL Parkville.
  • “Sputum analysis in bronchiectasis, immunodeficiency”, Dr Alex Schaub, CSL Berne.
  • “New models for fibrosis”, Dr Mike Wilson, CSL Parkville.
  • “The pharmacology of passive force in airway smooth muscle”, Prof Chun Seow, iCapture, UBC, Vancouver, Canada.
  • “Respiratory health of Mine workers”, Mr Pat Brady (Pump Investments Ltd), Dr Brian Plush (PM10).
  • “Casein kinase 1d splice variants: distribution, function and utility as pharmacological targets”, A/Prof Jean-Michel Fustin, Manchester University.
  • “Rotary planar multiplexed microfluidics (RPM2) pump”, Dr Andrew Gooley, Trajan Scientific and Medical.
  • “Models for COVID19 infection”, Dr Michelle Baker, Centre for disease preparedness, CSIRO, Geelong.
  • “Bioluminescent receptor signalling probes”, Prof Kevin Pfleger, Harry Perkins Institute, UWA.
  • “Apatamer biosensors”, Prof Kevin Plaxco, UCSD.

Funding

The Laboratory receives funding from the following bodies:

  • ARC
  • NHMRC
  • Asthma Australia
  • CSL

Research Publications

For a full list of publications go to Professor Stewart's ‘Find an Expert’ profile.

2023

  • AG Stewart, D Denoyer, X Gao, YC Toh (2023). The FDA modernisation act 2.0: bringing non-animal technologies to the regulatory table Drug Discovery Today, 103496.

2022

  • Meina Li and Alastair Stewart (2022). Translational Pharmacology in clinical trials. Comprehensive Compendium of Biomedical Science (Elsevier). https://doi.org/10.1016/B978-0-12-820472-6.00028-1.
  • KH Benam, JK Burgess, AG Stewart (2022). Accelerated Translation Using Microphysiological Organoid and Microfluidic Chip Models. Frontiers in Translational Pharmacology 12:827172. doi: 10.3389/fphar.2021.827172.
  • Qianyu Chen, Shenna Langenbach, Meina Li, Yuxiue Xia, Xumei Gao, Matthew J Gartner, Elizabeth A Pharo, Sinéad M Williams, Shawn Todd, Nadeene Clarke, Sarath Ranganathan, Michelle Baker, Kanta Subbarao Alastair George Stewart (2022). ACE2expression in organotypic human airway epithelial cultures and airway biopsies. Frontiers in Translational Pharmacology Volume 13.  https://doi.org/10.3389/fphar.2022.813087.
  • Gao, Xumei; Wu, Yanqi; Cheng, Tianhong; Stewart, Alastair (2022). Comprehensive Multiplexed Superfusion System Enables Physiological Emulation in Cell Culture: Exemplification by Persistent Circadian Entrainment. Lab on a Chip DOI: 10.1039/D1LC00841B.

2021

  • Cameron N Johnstone, Yan Tu, Shenna Langenbach, David Baloyan, Andrew D Pattison, Peter Lock, Kara L Britt, Brian D Lehmann, Traude H Beilharz, Matthias Ernst, Robin L Anderson, Alastair G Stewart. (2021) Annexin a1 is required for efficient tumor initiation and cancer stem cell maintenance in a model of human breast cancer. Cancers 13 (5), 1154.
  • Suowen Xu, Iqra Ilyas, Peter J. Little, Hong Li, Danielle Kamato, Xueying Zheng, Sihui Luo, Zhuoming Li, Peiqing Liu, Jihong Han, Ian C. Harding, Eno E. Ebong, Scott J. Cameron, Alastair G. Stewart, Jianping Weng. (2021) Endothelial dysfunction in atherosclerotic cardiovascular diseases and beyond: from mechanism to pharmacotherapies. Pharmacological Reviews 73 (3), 924-967.
  • Wu, Yanqi; Stewart, Alastair; Lee, Peter (2021). High-throughput microfluidic compressibility cytometry using multi-tilted-angle surface acoustic wave. Lab on a chip 21 (14), 2812-2824.
  • J Chatelier, S Chan, JA Tan, AG Stewart, JA Douglass (2021). Managing Exacerbations in Thunderstorm Asthma: Current Insights. Journal of Inflammation Research 14, 4537.
  • Jo A Douglass, Caroline Lodge, Samantha Chan, Alice Doherty, Ju Ann Tan, Celina Jin, Alastair G. Stewart, Anne Marie Southcott, Andrew Gillman, Joy Lee, Danny Csutoros, Liam Hannan, Laurence Ruane, Sara Barnes, Lou Irving, Nur-Shirin Harun, Phillipe Lachapelle, Kymble Spriggs, Michael Sutherland, Katherine See, Christine F McDonald, Matthew Conron, Nagmeh Radhakrishna, Christopher Worsnop, Fay Johnston, Janet M Davies, ,Vanessa Bryant, Linda Iles, David Ranson, Paresa Spanos, Don Vicendese, Adrian Lowe, Edward J Newbigin, Philip Bardin, Shyamali Dharmage,. (2021). Thunderstorm Asthma in Seasonal Allergic Rhinitis: The TAISAR study. J. Allergy Clin Immunol. https://www.jacionline.org/article/S0091-6749(21)01689-4/fulltext DOI: https://doi.org/10.1016/j.jaci.2021.10.028.

2020

  • Wu, Y. Tianhong Cheng, Qianyu Chen, Bryan Gao, Stewart, AG & Lee, PV. (2020). On-chip surface acoustic wave and micropipette aspiration techniques to assess cell elastic properties. Biomicrofluidics. https://doi.org/10.1063/1.5138662.
  • Asres Berhan, Trudi Harris, Jade Jaffar, Fernando Jativa, Shenna Langenbach, Ingrid Lönnstedt, Monther Alhamdoosh, Milica Ng, Peter Lee, Glen Westall, Nick Wilson, Michael Wilson, Alastair G Stewart. (2020). Cellular microenvironment stiffness regulates eicosanoid production and signaling pathways. American Journal of Respiratory Cell and Molecular Biology 63 (6), 819-830.
  • C Peng, AG Stewart, OL Woodman, RH Ritchie, CX Qin Non-Alcoholic Steatohepatitis: A Review of Its Mechanism, Models and Medical Treatments. Frontiers in Pharmacology 11, 1864.
  • Y Jin, K Shi, X Gao, SY Langenbach, M Li, T Harris, AG Stewart (2020). An Automated Quantitative Method to Analyze Immunohistochemistry and Immunocytochemistry Images. Journal of Engineering and Science in Medical Diagnostics and Therapy 3 (4).

2019

  • Yan Tu, Cameron N. Johnstone, James Ryall, Guillermo L. Campos, Ebony Fietz, Christine R Keenan, Alastair G Stewart. (2019). An MDA-MB-231 cell subline selected for highly metastatic phenotype shows increased oxidative phosphorylation. Journal of Cancer Metastasis and Treatment. DOI:10.20517/2394-4722.2018.67.
  • Meina Li, Christine R. Keenan, Guillermo Lopez-Campos, Jonathan E. Mangum, Qianyu Chen, Danica Prodanovic, Yuxiu C. Xia, Shenna Y. Langenbach, Trudi Harris, Vinzenz Hofferek, Gavin E. Reid, Alastair G. Stewart. (2019). Cofilin1 phosphorylation: a novel noncanonical pathway with potential for safer modulation of TGF-b1 in airways disease. iScience https://doi.org/10.1016/j.isci.2019.01.023.
  • Wu, Y. Stewart, AG & Lee, PV. (2019). On-chip cell mechanophenotyping of different cell types using surface acoustic wave. Biomicrofluidics. https://doi.org/10.1063/1.5084297.
  • Stewart, A.G. (2019). Engineering drug discovery technologies: clinical trial on-a-chip. Current Opinion in Pharmacology, 48:1-3. https://doi.org/10.1016/j.coph.2019.09.013.
  • Elham Bidram, Yasaman Esmaeili, Hadi Ranji-Burachaloo, Nuha Al-Zaubai, Ali Zarrabi, Alastair Stewart, Dave E. Dunstan. (2019). A concise review on cancer treatment methods and delivery systems. Journal of Drug Delivery Science and Technology 54, 101350.
  • Jean-Michel Fustin, Meina Li, Bryan Gao, Qianyu Chen, Tianhong Cheng, Alastair G. Stewart. (2019). Rhythm on a chip: circadian entrainment in vitro is the next frontier in body on-a chip technology. Current Opinion in Pharmacology. 48:127-136. https://doi.org/10.1016/j.coph.2019.09.005.

2018

  • Cameron N. Johnstone. Andrew D. Pattison, Kylie L. Gorringe, Paul F. Harrison, David R. Powell, Peter Lock, David Baloyan, Matthias Ernst, Alastair G. Stewart, Traude H. Beilharz and Robin L. Anderson. (2018). Functional and genomic characterisation of a xenograft model system for the study of metastasis in triple-negative breast cancer. Disease Models and Mechanisms. (11) doi:10.1242/dmm.032250.
  • Prodanovic D, Keenan CR, Langenbach S, Li M, Chen Q, Lew MJ, Stewart AG. (2018). Cortisol limits selected actions of synthetic glucocorticoids in the airway epithelium. FASEB J. 2018 Jan 3: doi:10.1096/fj.201700730R.
  • Philippe LaChapelle, Meina Li, Jo Douglass, Alastair Stewart. (2018). Safer approaches to therapeutic modulation of TGF-beta signaling for respiratory disease. Pharmacology and Therapeutics. doi.org/10.1016/j.pharmthera.2018.02.010.
  • Christine R. Keenan, Shenna Y. Langenbach, Fernando RJ Guzman, Jade Jaffar, Danica Radojicic, Trudi Harris, Michael J. Schuliga, Glen Westall, Alastair G. Stewart. (2018). Novel anti-fibrotic effects of casein kinase 1δ/ε inhibitor PF670462. Frontiers in Translational Pharmacology, doi:10.3389/fphar.2018.00738.
  • Elham Bidram, Adrian Sulistio, Ellie Cho, Trudi Harris, Greg Qiao, Alastair Stewart, Dave E. Dunstan. (2018). Targeted graphene oxide-based networks: cytotoxicity and synergy with anticancer agents. ACS Applied materials and interfaces, DOI: 10.1021/acsami.8b17531.
  • Alastair G Stewart, Belinda Thomas, Jon Koff (2018). TGF‐β: Master regulator of Inflammation and fibrosis. Respirology. DOI: 10.1111/resp.13415.

2017

  • 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.

2016

2015

Research Projects

For project inquiries, contact our research group head.


Faculty Research Themes

Infection and Immunology

School Research Themes

Therapeutics & Translation


Key Contact

For further information about this research, please contact Head of Laboratory Professor Alastair Stewart

Department / Centre

Biochemistry and Pharmacology

Unit / Centre

Alastair Stewart laboratory

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