Dr. Allan Murray is currently appointed as Associate Professor in the Division of Nephrology in the Faculty of Medicine and Dentistry.
We have a longstanding interest in the mechanisms of small-vessel injury affecting solid organ transplants. It is now recognized that the icrovessel 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 moleculeexpression 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.
cell movement, endothelial cell, endothelium, vascular, in vivo imaging, neovascularization, signal transduction, transplantation
Targeting PI3-kinase isoforms to inhibit tumor neovascularization
- Funding Source: Canadian Cancer Society
- Year Granted: 2017