Faculty: John Semple, PhD
Professor, Pharmacology, Medicine and Laboratory Medicine and Pathobiology
Head, Transfusion Medicine Research, Toronto Platelet Immunobiology Group, St. Michael's Hospital
Adjunct Scientist, Canadian Blood Services
General Research Area: Immunopharmacology.
T Cell Regulation of the Anti-platelet Antibody Response.
My research is aimed at understanding the cellular immune mechanisms responsible for the generation of IgG antibodies that recognize platelet antigens. These antibodies can lead to clinically significant adverse effects such as autoimmunity causing immune thrombocytopenia (ITP) and alloimmunity causing platelet transfusion refractoriness. In ITP, we are interested in how platelet antigens are processed and presented by antigen-presenting cells to activate T lymphocytes. In platelet refractoriness, we study the pro-inflammatory nature of platelets responsible for adverse reactions during platelet transfusions, particularly how platelet Toll-like receptor expression modulates innate immune mechanisms. We also study the recipient immune mechanisms that cause Transfusion Related Acute Lung Injury (TRALI), a serious complication of transfusion. We are also interested in understanding how therapies such as intravenous gammaglobulin (IVIg) and anti-D increase platelet counts in immune thrombocytopenic disorders.
Semple JW, Aslam R, Kim M, Speck ER, Freedman J. Platelet-bound lipopolysaccharide enhances Fc receptor-mediated phagocytosis of IgG opsonized platelets. Blood. 109(11):4803-4805, 2007.
Kjaersgaard M, Aslam R, Kim M, Speck ER, Freedman J, Stewart DIH, Wiersma EJ, Semple JW. Epitope specificity and isotype of monoclonal anti-D antibodies dictate their ability to inhibit phagocytosis of opsonized platelets. 2007. Blood. 110(4): 1359-1361, 2007.
Aslam R, Kim M, Speck ER, Contram Seetanah A, Molinski S, Freedman J, Semple JW. Platelet and erythrocyte phagocytosis kinetics are differentially controlled by phosphatase activity within mononuclear cells. Transfusion 47(11): 2161-2168, 2007.
Aslam R, Speck ER, Kim M, Freedman J, Semple JW. Transfusion-related immunomodulation (TRIM) by platelets is dependent on their expression of MHC class I molecules and is independent of leukocytes. Transfusion 48(9):1778-1786, 2008.
Semple JW Speck ER, Fabron Jr A, Aslam R, Kim M, Freedman J. A novel immunosuppressive pathway involving peroxynitrite-mediated nitration of platelet antigens within antigen presenting cells. Transfusion 48(9):1917-1924, 2008.
Chow L, Speck ER, Kim M, Aslam R, Webster M, Chen O, Ni H, Sahib K, Garvey MB, Sheridan BL, Freedman J, Semple JW. A novel mouse model demonstrating both antibody- and T cell-mediated thrombocytopenia: Differential response to IVIG. Blood, Blood First Edition Paper, prepublished online December 10, 2009; DOI 10.1182/blood-2009-09-244772.
St. Michael's Hospital
Li Ki Shing Knoweldge Institute
30 Bond Street