Academic Faculty

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Allan Murray, MD, FRCP(C)

Associate Professor

Medicine & Dentistry

Medicine

About Me


Research

Research Interests: We have a longstanding interest in the mechanisms of small-vessel injury affecting solid organ
transplants. It is now recognized that the microvessel endothelium of a transplanted heart or kidney is
subject to direct attack from the host immune system. Indeed, this appears to be the principal immune injury that
limits solid-organ allograft survival, hence represents a major cause of morbidity and mortality among Canadians
with end-stage organ dysfunction managed by transplantation. The mechanism(s) of endothelial injury are shared
among diseases collectively grouped as thrombotic microangiopathies, that by damaging the microvascular
endothelium cause acute or chronic organ failure. The diverse causes of the injury include hereditary genetic
mutations (e.g. complement regulatory proteins), infectious diseases (e.g. Shiga-like toxigenic infections), and
autoimmune disease (e.g. systemic lupus erythematosis, anti-phospholipid antibody syndromes).
Research Experience Summary: We have focused on 2 principal areas: i) recruitment of leukocytes by the
endothelium, ii) endothelial repair/ angiogenesis. We have studied regulation of endothelial adhesion molecule
expression and function, cytoskeletal remodeling of the inter-endothelial and basal adhesive contacts of the
endothelium, and defined intracellular signaling events that govern these. We have focused specifically on the
PI3 kinase/ mTOR/ and Rho GTP-binding protein signal transduction pathways to identify critical control nodes in
the endothelial cell that may be amenable to therapeutic intervention. This work has been supported by the use
of in vivo models of the diseases in mutant mice, and sophisticated in vitro models that robustly recapitulate key
features of the disease process in the human. Where feasible, we have exploited primary human endothelial cells
both in in vivo models and in vitro assays of microvascular repair in 2 and 3 dimensions.


Teaching