Research Group

  • Dr. Simon C. Robson, Principal Investigator
  • Dr. Imrana Qawi, Research Associate


  • Beth Israel Deaconess Medical Center, Boston, USA


  • Disordered Thromboregulation in Xenotransplantation

Clinical transplantation is limited by the availability of suitable human organ donors. The proposed use of an unlimited supply of animal organs in clinical practice (xenotransplantation) could provide a bridge to a later successful human graft in a critically ill patient, or more optimistically may even substitute for such a graft. Unfortunately, the clinical application of xenotransplantation has resulted in almost total failure to date.

Recent developments in the fields of xenotransplantation and vascular biology have greatly expanded our understanding of the mechanisms by which xenografts are rejected and have given new hope to the field. However, one additional novel barrier observed is the molecular incompatibility between natural anticoagulants expressed by blood vessels of pig organs and primate/human blood coagulation factors and platelets. This results in clotting within transplanted porcine xenografts in baboons, with rapid loss. To mitigate against these effects, we propose to derive triple transgenic animals overexpressing two human natural anticoagulants (tissue factor pathway inhibitor and thrombomodulin) and the thromboregulatory factor CD39 that profoundly inhibits the activation of platelets irrespective of the species of origin.

This project is a preliminary component of a long-term clinical xenotransplantation strategy ultimately involving the genetic modification of donor pigs to render them biologically more compatible. We will first investigate whether the respective human cDNAs can be functionally expressed in porcine vascular endothelium, either individually or in tandem. We then propose derivation of multi-transgenic mice, again checking that there are no deleterious effects of these combinations and testing the function of the overexpressed factors in relevant models of xenograft rejection.

This work will be judged successful if the data are of potential relevance for clinical transplantation and result in the testing of novel treatments to prolong xenograft survival.