Adrian West, Assistant Professor
Research Interests

The regulation of cellular function by the mechanical environment, termed mechanobiology, is a rapidly-emerging field of scientific research. This field has been predominantly enabled and driven by the development of new technologies and experimental models that have allowed cellular function to be studied in a more realistic environment than the very stiff and flat plastic of traditional cell culture models. Seminal work involved the creation of a polyacrylamide hydrogel model in which substrates with a tuneable stiffness are bonded to glass coverslips through silanes, and are coated with extracellular matrix (ECM) proteins through a heterobifunctional crosslinker. With this model it has been shown that cells are capable of sensing and probing the mechanical environment, which strongly regulates numerous basal cell functions including migration, adhesion and proliferation. More importantly, substrate stiffness alone can drive the differentiation of mesenchymal stem cells into different lineages, and is capable of over-riding traditional signalling pathways.

There are numerous mechanisms by which mechanical cues may profoundly alter traditional cell signalling paradigms and alter cellular function. These mechanisms are largely mediated through sites of mechanical coupling to the ECM (i.e. integrins and focal adhesions) and act through the cytoskeleton to alter receptor membrane targeting and clustering (e.g. at caveolae), translocation of activated transcription factors, and modify the arrangement of DNA within the nucleus by rapidly altering nuclear mechanics. However, the broader physiological consequences of mechanobiology regulation in health and disease are largely unknown.

The lung represents a physiological system in which these mechanobiology principles may play an important role; it contains a variety of mechanical microenvironments that range from very stiff cartilaginous trachea to highly compliant terminal bronchioles, plus important mechanical interdependencies between multiple systems (airways and vasculature) and cell types (epithelium/endothelium and muscle/fibroblast cells). Critically, a diverse spectrum of chronic lung diseases are characterised by alterations in structural and mechanical properties of the organ, including but not limited to asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and persistent pulmonary hypertension of the newborn (PPHN).

The overreaching aim of the West laboratory is to improve our understanding of how mechanobiology principles and structural/mechanical changes contribute the pathogenesis of lung disease. This aim presently incorporates three specific research direction:

  1. Ongoing development of cutting-edge tools to manipulate the cellular mechanical environment and measure innovative endpoints. This includes polyacrylamide hydrogels, 3D tissue-engineered smooth muscle, epithelial Transwell culture systems, and ex vivo lung tissue.
  2. Understanding the basal regulation of lung cellular function by mechanobiology, particularly relating to the contractile function of airway and pulmonary vascular smooth muscles and the barrier function of airway epithelium.
  3. Examining synergistic interactions between mechanobiology and traditional signalling pathways. This includes but is not limited to TGF-beta and RhoA signalling pathways, and how/where these pathways interact at focal adhesions, caveolae and the cytoskeleton.


Academic Achievements

  • BSc (Hons, Physiology), University of Western Australia, 2001
  • PhD (Physiology), University of Western Australia, 2007
  • Postdoctoral Research Associate, University of Western Australia, 2007 – 2009
  • Postdoctoral Fellow, Dalhousie University, 2009 – 2013
  • Assistant Professor, University of Manitoba, 2013 – present


Relevant Publications

Noble PB, Pascoe CD, Lan B, Ito S, Kistemaker LEM, Tatler AL, Pera T, Brook BS, Gosens R, West AR. Airway smooth muscle in asthma: linking contraction and mechanotransduction to disease pathogenesis and remodelling. Pulm Pharmacol Ther (2014); http://dx.doi.org/10.1016/j.pupt.2014.07.005

  • West AR, Zaman N, Cole DJ, Walker MJ, Legant WR, Boudou T, Chen CS, Favreau JT, Gaudette GR, Cowley EA, Maksym GN. Development and Characterisation of a 3D Microtissue Culture Model of Airway Smooth Muscle. Am J Physiol Lung Cell Molecular Physiol. (2013); 304(1): L4-16.
  • Awarded “Outstanding Junior Investigator Award” by the American Physiological Society. Feature Article on journal website Dec 2012 – March 2013
    Top “Editor’s Pick” 1st quarter 2013
    Journal cover article
  • Wright D, Sharma P, Ryu M, Rissé PA, Ngo M, Maarsingh H, Koziol-White C, Jha A, Halayko A, West AR. Models to study airway smooth muscle contraction in vivo, ex vivo and in vitro: implications in understanding asthma. Pulm Pharmacol Ther (2013); 26(1): 24-36.


Lab Members

  • Emily Turner-Brannen, Technician
  • Neilloy Roy, Master’s Student

Related Sites

Manitoba Institute of Child Health
Adrian West
Physiology & Pathophysiology

Tel: 204 789 3603

560 John Buhler Research Ctr

Adrian.West@umanitoba.ca

 


I am currently considering applications from students for MSc and PhD programs. Please send your CV and description of your research and academic interests to the email address noted above.

Adrian West