Research Group

  • Dr. Christiane Ferran, Principal Investigator
  • Dr. Mark Fisher, Surgical Resident/Research Fellow
  • Ms. Sowmya Sennani, Research Associate


  • Beth Israel Deaconess Medical Center, Boston, USA


  • Role of A20 upon Homing of EC and SMC Progenitors to Lesions of Transplant Arteriosclerosis

Effective immunosuppressive regimens used in transplantation have drastically reduced the failure of vascularized grafts due to acute rejection (<10%). Chronic rejection is the major obstacle to long-term transplant function. Chronic rejection is characterized by the development of an accelerated arteriosclerosis, termed transplant arteriosclerosis (TA). TA is particularly dramatic in cardiac transplant recipients and has become the principle cause of late death and graft dysfunction. Mechanisms of chronic rejection and TA are poorly understood and likely multifactorial (immunological and non-immunological causes). Recently, homing of progenitor endothelial and smooth-muscle cells (EC; SMC) have also been implicated in modulation of TA lesions.

Numerous approaches (including increased immunosupression, anti-hypertensive and lipid lowering agents) to treating TA have been largely unsuccessful and carry additional toxicity. We propose a novel anti-TA approach aimed at shielding the blood vessel from immune and non-immune effectors of TA. Our approach is based on our finding that the fate of the graft does not solely depend upon the host immune and non-immune effectors, but also on its ability to protect itself from injury. Our data suggest that this might be safely achieved by genetic engineering of the vessel wall with a single gene: A20. A20 is a physiologic protective response to injury in EC and SMC, preventing TA regardless of the precipitating offender. A20 is anti-inflammatory and anti-apoptotic in EC. A20 is anti-inflammatory and anti-proliferative in SMC and sensitizes abnormal SMC to death. In addition, A20 may promote homing of progenitor EC, which accelerates healing, while inhibiting recruitment, differentiation and survival of the deleterious progenitor SMC. We aim to provide direct in vivo proof of the protective effect of A20 against TA mainly regarding its role upon homing of EC and SMC progenitors. This could provide novel therapeutic leads to protect from TA and other vascular diseases.