Grants Funded

Abstract
Islet transplantation is considered to be a potentially definitive treatment for type 1 diabetes. Although there have been many successful transplants, there is a critical need to increase functional efficacy of small islet cell loads by optimizing engraftment and eliminating the need for chronic immunosuppression for graft survival.
We have developed a therapy utilizing proprietary cytokine fusion proteins for specifically targeting “modulation” of activated cytotoxic T cells and local recruiting regulatory T cells to promote long-term engraftment in stringent allotransplant models. However, islet allograft tolerance was not achieved in spontaneous autoimmune diabetic mice, possibly due to loss of sustained activity of the biologics. A biopatterning technology developed by our cooperative team at Carnegie Mellon University holds clear potential to improve therapeutic outcomes. This unique process enables spatial patterning of biologics, growth factors, or drugs immobilized within a biodegradable delivery matrces to control cell and tissue function. One matrix that we regularly use is DermaMatrix, which is a human allograft acellular dermal matrix maintaining the integrity of the matrix that can sequester or bind a broad range of growth factors, cytokines and their modifiers. Thus, we hypothesize that localized delivery of small doses of immobilized pro-regulatory agents and beta-cell growth factors to transplanted islets using biopatterning DermaMatrix will promote engraftment, function and long-term tolerance for islet transplant.
In this project we will demonstrate that localized delivery of combinations of solid-phase pro-regulatory fusion proteins and beta-cell growth factors, biopatterned in DermaMatrix, in adjunct with minimal islet allograft loads will achieve engraftment and tolerance with functional glucose homeostasis in autoimmune non-obese diabetic (NOD) recipients. Successful completion of the project will provide the promise for DermaMatrix as a carrier for delivery of immunoregulatory and islet promoting therapies and likely lead to a safe, effective and pro-tolerogenic approach for organ transplantation.

Biography
I obtained my M.D. and Ph.D. from Capital Medical University, China, where I worked as an attending doctor and was a PI on two research grants founded by Capital Medical Development Fund and Beijing Science Fund. I started my postdoctoral research at Harvard Medical School in 2007 and continued my work at University of Pittsburgh. Now I am a Research Instructor in the Department of Plastic Surgery. My researches focus on the basic mechanisms and novel strategies that generate and maintain tolerance in autoimmune diseases and organ transplantation. Over the last 8 years, I have been awarded the JDRF Postdoctoral Fellowship Grant and the PSEF Pilot Research Grant. I have also received Award of Distinguished Fellow and Young Investigator Award by American Society of Transplantation.