My research focuses on transplant tolerance strategies and mechanisms, particularly for islet cell transplantation as a curative therapy for autoimmune diabetes. Our primary approach is to use a donor-specific negative vaccination strategy to target the host machineries involved in the clearance of cellular apoptotic debris in an immune-tolerogenic fashion. We have shown that such a strategy is highly efficacious for induction of allogeneic as well as xenogeneic tolerance in murine models of allogeneic and xenogeneic islet cell transplantation. Our primary goal is now to translate this approach to clinical applications for human islet cell transplantation. Using non-human primate models, we are currently testing the efficacy of this strategy in monkey-to-monkey and pig-to-monkey islet cell transplantation, as well as developing appropriate standard operating procedures (SOPs) in preparation for future human applications. A further innovative way for delivery of negative vaccinations for tolerance induction is to engineer apoptotic and tolerogenic signals to biosynthetic nanoparticles that are attached with donor antigens, an endeavor we are currently making in collaboration with nanotechnology and material scientists. In addition, we are also testing bioengineered synthetic scaffolds as a more efficient platform for human islet cell transplantation than the intra-portal route, which is currently used in clinical practice. The ultimate goal of our research is to achieve clinical tolerance in human islet cell transplantation using simple but robust negative vaccinations exploiting host tolerogenic machineries.