The major research thrust of Dr. Robson's laboratory has been to elucidate the importance of the vascular ecto-nucleotidases of the CD39 family. These ecto-enzymes catalyze the hydrolysis of extracellular nucleotides, inhibit platelet and endothelial cell activation and are crucial for the vascular integrity of transplanted grafts. Dr. Robson and his colleagues were the first to identify ecto-nucleotidase activity in the vasculature of transplanted organs and shortly thereafter confirmed that CD39 (a hitherto B lymphocyte marker) had identity with the ATP or nucleoside triphosphate diphosphohydrolase (EC 22.214.171.124; NTPDase1 or ENTPD1). The observation that the ecto-nucleotidase activity of vascular CD39 is rapidly lost when grafts or native organs were subjected to reperfusion injury or oxidative reactions provided an explanation for the accumulation of platelets at sites of vascular injury.
His laboratory has defined the general topology of CD39 and portions of the molecule that are responsible for NTPDase function. Post-translational modifications of CD39 have been characterized. These modulate activity and expression of active enzyme on the cell membrane; for example, palmitoylation has been observed to occur at a single defined Cys on the N-terminal portion of CD39 that stabilizes membrane association. Acylation also facilitates caveolar targeting that may be important in cellular signaling by nucleotides and interactions with P2 receptors and scaffolding molecules e.g. RanBPM.
Dr. Robson, Dr Enjyoji and colleagues generated and characterized cd39-deficient and CD39 transgenic mice. These model systems indicate roles for CD39 in modulating P2 receptor function in the context of hemostatic, inflammatory and thrombotic reactions and also angiogenesis. Reconstitution of NTPDase activity by infusion of soluble enzyme, gene therapy with adenoviral vectors or the development of transgenic animals (mice and swine) with high level expression of CD39 have demonstrated the potential of vascular NTPDase to both prolong graft survival and inhibit platelet sequestration at sites of vascular injury.
These data have validated the role of extracellular nucleotides in mediating vascular inflammation, and have successfully addressed a hitherto controversial and important area in vascular biology. His discoveries are of importance in understanding the role of extracellular nucleotides in mediating thrombosis, inflammation and vascular growth and remodeling.
Recent work has detailed the functional consequences of CD39 expression by dendritic cells and regulatory T cells.
His laboratory has been also specifically addressing abnormalities associated with alterations in coagulation and hemostasis in transplanted organs, including xenografts. Importantly, Dr. Robson has also observed several cross-species' molecular incompatibilities that are highly relevant for the control of coagulation and hemostasis within a xenograft. This discovery and the realization that xenograft rejection is, at least in part, mediated by molecular incompatibilities with respect to the regulation of coagulation has opened up new therapeutic avenues with the development of transgenic animals that may result in ultimate clinical application of islet xenotransplantation.
From 1995 to 2000, Dr. Robson held a visiting Associate Professorship in Medicine at Harvard University. In 1997, Dr. Robson took up a position as Staff Gastroenterologist at Beth Israel Deaconess Medical Center. He was appointed as Associate Professor in Medicine at the Harvard Medical School in 2000 and as Full Professor in 2006
He is currently involved in undergraduate and postgraduate teaching and the running of Liver Transplantation and clinical Hepatology services at the Beth Israel Deaconess Medical Center.
His primary clinical focus has remained Hepatology with clinical interests in hepatic vascular diseases and viral hepatitis.