Our research laboratory focuses on two issues: 1)overcoming problems related to allogenicity in transplantation and 2) the role of endotoxin neutralization in mitigating the toxicity of radiotherapy.
In regard to the first, allogeneic transplantation is limited by immune attacks between donor and host. Global immunosuppression has been an incomplete and highly toxic approach to this problem. Current understanding of T cell activation suggests that blocking B7-CD28 interactions of the costimulatory pathway for human T helper cells provides an innovative way of producing antigen-specific T cell hyporesponsiveness and generation of regulatory T cells. We are applying these various strategies to the transplant setting.
In regard to the second area, we have found that a human endotoxin neutralizing molecule, bacteriacidal permeability increasing protein (BPI), has the capacity to dramatically decrease the side effects of radiation. We are pursing these observations both for emergency use (such as a nuclear accident) but also in terms of effects on chemoradiotherapy of cancer.