Simon Robson

Research over the past years has illustrated protean biologic effects of ATP, ADP, and adenosine-mediated signaling. These mediators function through the activation of G-protein–coupled or ligand-gated ion-channel receptors. Adenosine is derived from ATP and ADP through the actions of enzymes such as CD39 and family members on cellular surfaces, which also express the receptors for these mediators. Since the receptors of ATP and ADP and the receptors of adenosine often transduce opposite effects, the resulting cellular response is attributable to both the ratio of ADP and ATP to adenosine concentrations and the relative levels of expression and signaling intensity of the respective receptors. 

The Robson laboratory has studied the functional roles of purinergic signaling in inflammatory diseases. The focus has been on the contribution of disordered inflammatory responses as modulated by ectoenzymes of the CD39 family to the fundamental mechanisms of acute and chronic disease. Specifically, CD39 has important functions in down regulating inflammatory processes and modulating innate immune responses within transplanted organs and at sites of inflammation in the liver and gastrointestinal tract. Research originally focused on the vascular biology of transplantation has extended to include innate immunology, adaptive cellular responses and tissue remodeling of the liver and gastrointestinal tract (as in hepatitis, cirrhosis and IBD). In the liver, CD39 is a crucial factor in vascular sinusoidal cell functionality and is important in the mediation of liver injury, and in further regulating liver regeneration and fibrosis. In the gut, CD39 is an important anti-inflammatory factor and low level expression ascribed to genetic polymorphisms in patients has been linked to IBD/Crohn’s disease.

His laboratory has also specifically addressed abnormalities associated with alteration in coagulation and hemostasis in transplanted organs, including xenografts. As an example, over expression of CD39 in transgenic grafts has demonstrated substantive benefits in graft functions and survival. These studies have opened up new therapeutic avenues with the development of transgenic animals that may result in ultimate clinical application of islet and organ xenotransplantation.