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islets of Langerhans • type 1 diabetes • cell death • inflammation • ischemia-reperfusion injury • immunoregulation
My research focuses on the response of transplanted tissues to injury and the way injury activates an immune response in the context of two types of transplants. Transplantation of pancreatic islets of Langerhans has the potential to reverse type 1 diabetes (also called juvenile diabetes). Injury to islet cells during their purification from the donor pancreas results in production of mediators which stimulate inflammation in the recipient. These include chemokines and products of cell death. We are currently studying several strategies to diminish this effect, and whether this leads to better engraftment and function of transplanted cells. In the context of kidney transplantation, we conduct an ongoing translational study looking at the recruitment of regulatory T cells to the graft immediately following transplantation. These cells diminish the immune response promote graft specific tolerance. Our studies examine individual patient variations in Treg function and how these are reflected in graft outcomes.
S Negi, A Jetha, R Aikin,C Hasilo, R Sladek and S Paraskevas, Analysis of beta-cell gene expression reveals inflammatory signaling and evidence of dedifferentiation following human islet isolation and culture, PLoS One, 2012;7(1):e30415.
GJ Prud'homme, Y Glinka, C Hasilo, S Paraskevas, Q Wang, GABA protects human islet cells against the deleterious effects of immunosuppressive drugs and exerts immunoinhibitory effects alone, Transplantation, 2013 Oct 15;96(7):616-23
S Negi, SH Park, A Jetha, R Aikin, M Tremblay and S Paraskevas, Evidence of endoplasmic reticulum stress mediating cell death in transplanted human islets, Cell Transplant, 2012; 21(5): 889-900.
LG Grunnet, R Aikin, MF Tonnesen, S Paraskevas, L Blaabjerg, J Størling, L Rosenberg, N Billestrup, D Maysinger, T Mandrup-Poulsen. Pro-inflammatory cytokines activate the intrinsic apoptotic pathway in &beta cells, Diabetes, 2009; 58(8): 1807-15
SC Hanley, S Paraskevas and L Rosenberg, Donor and isolation variables predicting human islet isolation success, Transplantation, 2008; 85: 950-55