Uncovering the interplay between innate immunity and the blood brain barrier in disorders of the CNS

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  Project Leader
  Professor Christine Wells

  wellsc@unimelb.edu.au

  View researcher's webpage

  + 61 3 8344 3795

Project Details

Vascular health is a crucial determinate in the fate of our CNS as we age. Disability is a consequence of ischemic stroke in >35% of individuals, and despite the major social and economic consequences, there are few effective interventions. Disruption of the blood-brain barrier is also a key factor in the pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness throughout the world. We have discovered that the C-type lectin, Mincle, is expressed on an otherwise poorly characterised perivascular-macrophage (PVM). Activation of Mincle in rodent models of ischemia-reperfusion promotes inflammatory cell recruitment, exacerbates tissue damage and delays recovery from ischemic stroke. Current projects in the laboratory are aimed at characterising the cells contributing to the function of the blood brain barrier, as well as the Mincle receptor and its role in neuroinflammation of the brain and eye.

Researchers

Nadia Rajab, PhD Student

Collaborators

Professor Erica Fletcher, Department of Anatomy and Neuroscience, University of Melbourne
Associate Professor Ben Hogan, University of Queensland
Dr Marc Ruitenberg, University of Queensland
Associate Professor Thirumum (Garrie) Arumagam, National University of Singapore
Professor I Mhairi Macrae,  University of Glasgow
Prof Nadia Rosenthal, The Jackson Laboratory
Dr Riccardo Natoli, The Australian National University

Funding

NHMRC Project Grant (2016-17): "The C-type lectin Mincle exemplifies a new mode of sterile inflammation in cardiovascular disease"

ARC Future Fellowship (2015-19): "The Systems Biology of Stem Cells"

Research Publications

• Arumugam TV et al. An atypical role for the myeloid receptor Mincle in CNS injury. Journal of Cerebral Blood Flow and Metabolism. (2016) In press
• Lee EJ et al. Mincle activation and the Syk/Card9 signaling axis are central to development of autoimmune disease of the eye. Journal of Immunology 2016; 196(7): 3148-3158.
• Wells CA et al. The macrophage inducible c-type lectin, Mincle, is an essential component of the innate immune response to Candida albicans. Journal of Immunology 2008; 180(11):7404-13.