Terry Fox Laboratory - BC Cancer Agency

Terry Fox Laboratory - BC Cancer Agency Terry Fox Laboratory - BC Cancer Agency

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British Columbia Cancer AgencyTERRY FOX LABORATORY33. Novel agents for hematopoietic stem cell expansionPI: K HumphriesCIHR POP$136,018 (2005)$136,018 (2005‐2005)The proposed work will investigate the effectiveness of novel stemcell expanding reagents and to develop them into reagents that canbe safely and efficiently used clinically.34. Optimization of the use of diphtheria toxin‐growth factor fusion proteins for the treatment of acuteleukemiaPI: D HoggeCIHR$22,918 (2005)$22,918 (2006)$68,754 (2004‐2006)The goal is to measure the level of expression of the targetreceptors on different leukemia samples and the proliferativeactivity the leukemia cells from these samples to determine if thesefeatures predict response to the DT‐GF molecules. We will alsodetermine if combining the DT‐GF molecule with another drugwhich targets leukemia cells will be more effective than either drugalone.35. Optimization of the use of diphtheria toxin‐growth factor fusion proteins for the treatment of acuteleukemiaPI: D HoggeNCIC$116,179 (2005)$116,179 (2006)$350,000 (2005‐2008)This project is investigating a different class of targeting moleculesin which the diphtheria toxin (DT) is fused to a growth factor (GF)molecule to target leukemic cells. The proposed studies willfacilitate the entry of new and improved molecules and patientselection strategies into clinical trials which may ultimatelyimprove anti‐leukemic therapy for patients with Acute MyeloidLeukemia.36. Receptors on NK and NKT cellsPI: F TakeiNCIC$145,368 (2005)$145,368 (2006)$735,438(2003‐2008)This goal is to study NKT cells in more detail. In particular, we willfind out what role NKT cells have in the immune system, whetherthey use the same receptors as NK cells to recognize healthy cells,and what factors stimulate their activity.37. Regulation of natural killer cell receptor genesPI: D MagerCIHR$127,700 (2005)$127,700 (2006)$638,500 (2004‐2009)38. Replicative shortening of telomeres in human cellsPI: P LansdorpCIHR$132,069 (2005)$132,069 (2006)$660,345 (2005‐2010)The goal is to elucidate the mechanisms that generate functionaldiversity of NK cells – the white blood cells considered to be thefirst line of immune defense against virus‐infected and cancer cells.The focus is on the receptors on NK cells that recognize MHCclass‐I molecules, and to employ the development of new ways toharness the body’s immune system to eliminate cancer cells.The goal is to investigate the role of the human RTEL (regulator oftelomere length) protein in the growth of normal and malignantcells. The objective of this study is to understand the role oftelomeres in aging and cancer by addressing specific questionsabout the molecular mechanisms of telomere loss.160

Biennial Research Report 2005 ‐200639. Role of DNA methylation in controlling syncytin: a novel gene implicated in multiple sclerosisPI: D MagerMultiple Sclerosis Society$35,000 (2005)$35,000 (2006)$70,000 (2005‐2006)40. Role of LFA‐1 in cell mediated cytotoxicityPI: F TakeiCIHR$58,632 (2005)$58,632 (2006)$586,315 (2005‐2010)41. Role of RasGRP1 in BCR‐induced deletion of immature B cellsPI: R KayCIHR$117,336 (2005)$117,336 (2006)$821,347 (2004‐2008)This project will investigate if the ERV transcriptional promoter ofthe syncytin gene is a sensitive target for epigenetic regulation andthat perturbations in this regulation may be involved in multiplesclerosis.The goal of this study is to understand how a protein called LFA‐1involved in cell‐cell binding acts to initiate the cascade of events toguide ‘killer lymphoctye’ cells of the immune system to attackdiseased cells.The goal is to understand the molecular mechanism by which RasGRP1 increases the sensitivity of immature B cells to survivalsignal suppression and induction of cell death. Insight intoregulation of B cell activation vs. deletion is critical to ensureeffective immune response to foreign antigens while avoidingauto‐immunity.TERRY FOX LABORATORY42. Role of retroelements in age related gene expressionPI: D MagerCIHR (Pilot Project)$49,942 (2005)$49,942 (2006)$100,000 (2006‐2007)43. Stem cell and gene regulationPI: A EavesCo‐PIs: C Eaves, D Hogge, PHoodless, K Humphries, RKay, G Krystal, P Lansdorp, DMager, C Smith, HSutherland, F TakeiMSFHR Research Unit$250,000 (2005)$250,000 (2006)$1,000,000 (2003‐2008)44. Stem cell centrePI: P LansdorpCFI$1,008,384 (2005)$1,008,384 (2006)$3,775,195 (2002‐2005)45. Stem cell centre ‐ infrastructure operating fundsPI: P LansdorpCFI$110,079 / yr (2005, 2006)$231,346 (2003‐2006)This project will investigate whether the gradual, age‐relateddemethylation of retroelements, located within or near genes canlead to altered expression of genes.This goal is to enhance studies to understand the molecularpathways that govern stem cell renewal, viability, theirdevelopment into specific types of cells, their ability to multiplyand their genome stability.This project will address new questions in stem cell biology andexplore emerging possibilities for the use of stem cells inregenerative medicine. The centre will comprise of threelaboratories: a stem cell sorting and analysis laboratory, a genevector laboratory and a Good Manufacturing Practice (GMP) StemCell Processing Laboratory.Partial infrastructure operating funds for the stem cell centreproject.161

British Columbia <strong>Cancer</strong> <strong>Agency</strong>TERRY FOX LABORATORY33. Novel agents for hematopoietic stem cell expansionPI: K HumphriesCIHR POP$136,018 (2005)$136,018 (2005‐2005)The proposed work will investigate the effectiveness of novel stemcell expanding reagents and to develop them into reagents that canbe safely and efficiently used clinically.34. Optimization of the use of diphtheria toxin‐growth factor fusion proteins for the treatment of acuteleukemiaPI: D HoggeCIHR$22,918 (2005)$22,918 (2006)$68,754 (2004‐2006)The goal is to measure the level of expression of the targetreceptors on different leukemia samples and the proliferativeactivity the leukemia cells from these samples to determine if thesefeatures predict response to the DT‐GF molecules. We will alsodetermine if combining the DT‐GF molecule with another drugwhich targets leukemia cells will be more effective than either drugalone.35. Optimization of the use of diphtheria toxin‐growth factor fusion proteins for the treatment of acuteleukemiaPI: D HoggeNCIC$116,179 (2005)$116,179 (2006)$350,000 (2005‐2008)This project is investigating a different class of targeting moleculesin which the diphtheria toxin (DT) is fused to a growth factor (GF)molecule to target leukemic cells. The proposed studies willfacilitate the entry of new and improved molecules and patientselection strategies into clinical trials which may ultimatelyimprove anti‐leukemic therapy for patients with Acute MyeloidLeukemia.36. Receptors on NK and NKT cellsPI: F TakeiNCIC$145,368 (2005)$145,368 (2006)$735,438(2003‐2008)This goal is to study NKT cells in more detail. In particular, we willfind out what role NKT cells have in the immune system, whetherthey use the same receptors as NK cells to recognize healthy cells,and what factors stimulate their activity.37. Regulation of natural killer cell receptor genesPI: D MagerCIHR$127,700 (2005)$127,700 (2006)$638,500 (2004‐2009)38. Replicative shortening of telomeres in human cellsPI: P LansdorpCIHR$132,069 (2005)$132,069 (2006)$660,345 (2005‐2010)The goal is to elucidate the mechanisms that generate functionaldiversity of NK cells – the white blood cells considered to be thefirst line of immune defense against virus‐infected and cancer cells.The focus is on the receptors on NK cells that recognize MHCclass‐I molecules, and to employ the development of new ways toharness the body’s immune system to eliminate cancer cells.The goal is to investigate the role of the human RTEL (regulator oftelomere length) protein in the growth of normal and malignantcells. The objective of this study is to understand the role oftelomeres in aging and cancer by addressing specific questionsabout the molecular mechanisms of telomere loss.160

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