The Robson laboratory addresses the importance of ectoenzymes of the CD39 family of ectonucleotidases expressed by endothelium, by regulatory immune and dendritic cells in transplantation biology and Hepatology. Research has largely focussed on the vascular pathobiology of transplant injury and is currently extending to include studies of vascular inflammation, angiogenesis and remodeling. These proteins hydrolyze extracellular nucleotides and have been shown to be crucial for the vascular integrity of transplanted grafts. CD39 functions by down regulating inflammatory processes and modulating innate immune responses within transplanted organs. High-level expression of CD39 using gene therapeutic modalities, following transgenesis or by infusion of soluble, pharmacologically active derivatives has salutary effects on both vascular injury and graft survival. Further work has been directed at determining the importance of CD39 in adaptive immunity, angiogenesis and regenerative medicine.
Recent collaborations between the Robson and Strom laboratories have resulted in the key observation that the phenotype of T regulatory cells can be characterized by dual surface expression of CD39 and CD73, another ectonucleotidase that operates in tandem to generate adenosine. Adenosine can be shown to be immune suppressive in both in vitro and in vivo systems. Hence CD39 and purinergic mechanisms are closely implicated in regulatory T cell suppressive functions.
Recent work has also shown that CD39 is also a crucial factor in angiogenesis and vascular sinusoidal cell expression is important in regulating liver regeneration.
The Robson laboratory also specifically addresses abnormalities associated with alterations in coagulation and resulting thrombosis in transplanted organs, including xenografts. The long-term strategy in collaboration with David Sachs and Tony d'Apice has been to generate transgenic animals/pigs that over-express CD39 and other human thromboregulatory factors e.g. thrombomodulin, within the vasculature. This novel approach will test resistance of transgenic organs and islets to the thrombotic microangiopathic form of xenograft rejection in non-human primates. This work if successful may lead to possible, future clinical evaluations, particularly in islet xenotransplantation.