Jon D. Piganelli, Ph.D, Assistant Professor
Ph.D., Oregon State University
RANGO
Pittsburgh, PA 15213
Phone: (412) 692-7498
Email: jdp51@pitt.edu
My laboratory studies T cell mediated effector mechanisms of beta cell destruction in Type I Diabetes (TID). Type I diabetes is an autoimmune process whereby T cells recognize pancreatic ?cell antigens and initiate a leukocyte infiltrate that produces pro-inflammatory cytokines and reactive oxygen species (ROS), ultimately causing ?cell destruction. ?cells have a reduced capacity to scavenge ROS and are therefore very sensitive to their actions. More specifically my laboratory focuses on understanding how the generation of reactive oxygen species (ROS) in chronic inflammation leads to pathological states in inflammatory mediated autoimmune disease. We are also interested in how the immune system uses the generation of ROS during immune activation to synergize the innate and adaptive immune response. Understanding how ROS facilitate the activation of the immune response allows us to exploit these pathways through therapeutic intervention. Through the use of a class of novel small molecule metalloporphyrin superoxide dismutase mimic (SOD mimic), we have begun to elucidate the role of oxidative stress in the development of autoimmune diabetes. Metalloporphyrin superoxide dismutase mimics (SOD-mimics) scavenge a broad range of ROS and protect cells from oxidative stress and apoptosis. Our work has demonstrated that through the use of a novel approach of free radical scavenging of ROS, using the SOD mimic, we can block T cell mediated generation of ROS and pro-inflammatory cytokines in an adoptive transfer system using the diabetogenic T cell clone BDC-2.5 ultimately preserving pancreatic ?cell function. We have ascertained that this mimic not only has immunomodulatory function but also may directly protect the islet ?cells from both pro-inflammatory cytokines and ROS destruction. We would like to extrapolate these studies for the generation of antigen-specific hyporesponsiveness in situation such as transplantation.
Recent Publication
Bottino R, Balamurugan AN, Tse H, Thirunavukkarasu C, Ge X, Profozich J, Milton M, Ziegenfuss A, Trucco M, Piganelli JD. Response of human islets to isolation stress and the effect of antioxidant treatment. Diabetes. 2004 Oct;53(10):2559-68.
Milton MJ, Poulin M, Mathews C, Piganelli JD. Generation, maintenance, and adoptive transfer of diabetogenic T-cell lines/clones from the nonobese diabetic mouse. Methods Mol Med. 2004;102:213-25.
Tse HM, Milton MJ, Piganelli JD. Mechanistic analysis of the immunomodulatory effects of a catalytic antioxidant on antigen-presenting cells: implication for their use in targeting oxidation-reduction reactions in innate immunity. Free Radic Biol Med. 2004 Jan 15;36(2):233-47.
Schott WH, Haskell BD, Tse HM, Milton MJ, Piganelli JD, Choisy-Rossi CM, Reifsnyder PC, Chervonsky AV, Leiter EH. Caspase-1 is not required for type 1 diabetes in the NOD mouse. Diabetes. 2004 Jan;53(1):99-104.
