Research Group

  • Dr Christopher Carman, Principal Investigator
  • Dr David Briscoe, Collaborator
  • Prof. Ann Dvorak, Collaborator
  • Prof. Christiane Ferran, Collaborator
  • Mr Peter Sage, Graduate Student
  • Prof. Arlene Sharpe, Collaborator
  • Dr Laya Varghese, Research Assistant


  • Beth Israel Deaconess Medical Center, Boston, USA


  • Understanding the Cell Biological Mechanisms of Transplant Rejection

During organ transplantation, specific white blood cell types of the host immune system (T cells) sense differences in proteins (MHC molecules) on the surface of the donated organ, which trigger immune responses and transplant rejection. Our research is aimed at understanding how vascular endothelial cells (which make up the inner lining of the circulatory system and display MHC proteins) on transplanted organs interact and communicate with host T cells in order to influence immune responses. In normal immune responses, T cells are given highly specific instructions from information gathering ‘sentinel’ immune cell types, antigen presenting cells (APCs), that use both MHC and another set of proteins (costimulators) to communicate. Information exchange is achieved by a highly ordered intimate cell-cell contact termed an ‘immunological synapse’. Details of the architecture, dynamics, duration of this contact, as well as the number and exact type of MHC and costimulatory molecules involved, encode distinct instructions: they may direct T cells to seek out and destroy invading pathogens, to become quiescent (i.e. tolerant to an antigen) or to themselves become positive (e.g. Th1 or Th17) or negative (Treg) regulators of other immune/inflammatory reactions. It is well established that vascular endothelial cells share some of the functions of APCs (e.g. display of MHC and certain costimulators) and in this way may be important determinants of the immune system’s response to transplanted tissues. However, exactly what instructions endothelial cells provide to T cells and specifically how they communicate these instructions (i.e. what the immunological synapse looks like) remains unknown. Our work focuses on developing the first detailed understanding of both the specific information that endothelial cells provide to T cells (that is, in which ways they alter immune responses) and precisely how this cell-to-cell communication takes place.

To accomplish these goals we will use cutting-edge microscopic approaches not previously applied to the transplant rejection pathology. In this way, our studies will strive to define the cellular and molecular details of this process for the first time. Doing so will provide significant potential to identify specific processes and/or molecules that could serve as targets for the development of new therapeutic approaches for transplant rejection.

Progress Report

Final Report