SINCLAIR, GARY D. - University of Calgary - Department of Biochemistry & Molecular Biology

个人简介

Ph.D. (Doctor of Philosophy)

研究领域

My laboratory is interested in hemostasis and hematopoietic cell transplantation in humans THEME 1: Hemostasis in hemophilia A and B. Hemostasis is altered in individuals with hemophilia due to inherited deficiency of clotting factor VIII (Hem A) or FIX (Hem B). Severe hemophilia A patients (FVIII <1%) bleed spontaneously, and require infusions of recombinant FVIII protein on a regular basis. Interestingly, the amount and/or frequency of replacement therapy varies between individuals with severe hemophilia A. Our research is focused on the possible mechanisms of this known heterogeneity, in particular using sensitive thrombin generation assays to investigate; if differences in residual levels of clotting factors under 1% normal level, as well as the amount and pattern of thrombin generation in patient's own plasma (as a test of overall hemostasis), could contribute to this phenotypic heterogeneity. THEME 2: Molecular techniques for monitoring leukemias and hematopoietic cell chimerism after bone marrow transplantation Blood cell cancers are treated with various chemotherapeutic agents, and with bone marrow or peripheral blood stem cell transplantation with curative intent. Success of these various treatments can be impacted by the return of cancerous cells or failure of engraftment. We have developed (for monitoring) a number of molecular assays specific for determining extent of residual leukemia cell population (recipient hematopoietic cell chimerism) after transplantation so that relapses or graft failures can be detected early. In collaboration with the Molecular Hematology laboratory at CLS, we are interested in the development of new, real-time PCR assays for determination of chimerism status after transplantation including the application of insertion/deletion polymorphism based PCR analyses.

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Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, Patel KD, Chakrabarti S, McAvoy E, Sinclair GD, Keys EM, Allen-Vercoe E, Devinney R, Doig CJ, Green FH, Kubes P. (2007) Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 13(4): 463-9. OwenCJ, Toze CL, Koochin A, Forrest DL, Smith CA, Stevens JM, Jackson SC, Poon M-C, Sinclair GD, Leber B, Johnson PRE, Macheta A, Yin JAL, Barnett MJ, Lister AT, and Fitzgibbon J (2008). Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy (FPD/AML). Blood 112(12):4639-45. Jackson SC, Sinclair GD, Cloutier S, Duan Z, Rand ML, and Poon M-C (2009). The Montreal Platelet Syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation. Blood 113(14): 348-51.