Transplantation is widely recognized as the treatment of choice for end stage organ disease in children. Nevertheless, despite significant advances in immunosuppressive therapeutics to prevent acute rejection, long-term graft survival remains suboptimal. For most transplanted organs, the rate of decline in function has not changed in over 20 years, and currently all grafts will eventually fail due to chronic rejection. The overall median survival of allografts remains suboptimal at ~6 years for lung, ~11 years for heart and ~15 years following kidney transplantation. Immunosuppressive agents have failed to reverse chronic allograft rejection, and, once established, supportive therapy is the best that can be currently offered to patients. It has therefore become most apparent that long term success following transplantation will require greater understanding of responses that both promote and inhibit chronic allograft rejection. There is also a huge need to develop mechanistic biomarkers to define the status of the alloimmune response and indices of graft injury so that new therapeutics can be developed.
Research in the Briscoe Laboratory relates to all these issues with a focus on the intragraft microenvironment, and how it functions to both promote and inhibit chronic rejection. Our studies focus on three broad areas, including: 1) immune-mediated angiogenesis and how angiogenesis factors function in the rejection process; 2) how leukocyte-endothelial cell interactions and products of these interactions promote, sustain or inhibit T cell activation and allorecognition; and 3) whether persistent events within the microvasculature are associated with, or mediate chronic allograft rejection. We are currently expanding our research effort into the area of inflammation resolution, and we are specifically interested in endogenous mechanisms and regulatory signaling networks of pro-resolution. Understanding these processes will allow us to develop new paradigms for anti-rejection therapeutics following transplantation.
Please visit the Briscoe Laboratory website to learn more.
Briscoe Laboratory, 2016