Biography – John Semple
Adjunct Scientist, Canadian Blood Services
Transfusion Medicine Research
Senior Staff Scientist
Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital
St. Michael's Hospital
30 Bond St.
Toronto, ON, M5B 1W8
- Animal models of platelet autoimmunity related to immune thrombocytopenia (ITP)
- The role of the innate immune system in initiating and regulating platelet autoimmunity and alloimmunity
- The antigen processing and presentation pathways of platelet allo- and auto-antigens within antigen presenting cells
- The immunopathophysiology of transfusion related acute lung injury (TRALI)
- The mechanism of action of Rh immune globulin (anti-D) in raising platelet counts in patients with ITP
- The role of platelet-TLR receptors in controlling innate immune responses
My research is aimed at understanding the cellular immune mechanisms responsible for generation of both auto- and allo-IgG antibodies that recognize platelet antigens. These mechanisms can be exploited to develop immune-specific therapies which suppress these clinically significant immune responses. We are interested in how platelet antigens are processed and presented by antigen-presenting cells to T lymphocytes and how these intracellular biochemical events control platelet immunity. The pro-inflammatory nature of platelets that may be responsible for adverse reactions from platelet transfusions is also of interest, particularly how platelet Toll-like receptor expression modulates innate immune mechanisms. We are also studying the mechanisms that intravenous gammaglobulin and anti-D preparations utilize to increase platelet counts in immune thombocytopenic 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.