Terry Fox Laboratory - BC Cancer Agency
Terry Fox Laboratory - BC Cancer Agency Terry Fox Laboratory - BC Cancer Agency
British Columbia Cancer AgencyTERRY FOX LABORATORY8. Cell therapy for muscular diseasePI: F Rossi (UBC)Co‐PI: K HumphriesStem Cell NetworkTotal to KH ‐ $96,000 (2005‐2008)9. Characterization of anti‐tumour activity of STEP‐1PI: C LuerCo‐PI: C SmithNIHTotal to CS ‐ $11,700 (2005‐2007)10. CIHR team grant in cell expansionPI: G Sauvageau (UMontreal)Co‐I: K Humphries, C EavesCIHR team grant$198,233 (2006)$1,000,000 (2006‐2011)The goal is to promote generation of hematopoietic stem cellsfrom murine embryonic stem cells.This project will characterize the activity of an apoptosis inducingfactor found in a natural extract using high throughput flowcytometric screening.The major goals are: 1) To gain a better understanding of howHox‐related genes regulate hematopoietic stem cell self‐renewaland 2) to use this information to evaluate the potential ofmanipulating Hox levels in patients’ stem cells to expand theirnumbers and improve transplantation‐based therapies wherestem cell numbers are limiting.11. Dependence of human embryonic stem cell self‐renewal on culture variablesPI: C EavesStem Cell Network$34,958 (2005)$323,600 (2003‐2005)The goal is to study how varying the environment under whichcells are grown will change the expression of different genes tobetter control stem cell growth and differentiation.12. Development of technologies for the derivation, propagation and differentiation of humanembryonic stem cells (HESC)PI: J. Piret (UBC), C Eaves, MBhatia, A NagyCo‐I:, K Humphries, P Lansdorp, AKarsan, M Marra, et alStem Cell Network$157,557 (2005)$157,557 (2006)This project will lay the groundwork for developing humanembryonic stem cell‐based therapies and facilitate the broader useof these cells to identify new drugs that stimulate or repressparticular regenerative events in vivo.13. Diagnosis of graft versus host disease using high throughput flow cytometeryPI: C SmithBC Transplant Foundation$30,000 (2006)$90,000 (2006‐2008)The goal is to analyze a previously collected data set comprised ofhigh throughput flow data obtained from peripheral bloodsamples at progressive time points following allogeneictransplantation to identify flow cytometric signatures of GvHD.14. Disease mechanisms in chronic myeloid lymphoma (CML)PI: A EavesCo‐PIs: C Eaves, X JiangNCIC$150,000 (2005)$150,000 (2006)$705,000 (2003‐2011)The goal is to study CML stem cells, since controlling or destroyingthese cells is necessary if CML is to be cured. We will look at howthe speed of CML cell multiplication is controlled; what are theproperties of these cells that cause leukemia to relapse; andwhether a mouse xenografting model can be used to predict theutility of new drugs for this disease.156
Biennial Research Report 2005 ‐200615. Dissecting gene expression networks in mammalian organogenesisCo‐PIs: P Hoodless, M MarraCo‐I: A Karsan, C Helgason, SJones, S Katz (UBC), E Levy(UBC)Genome Canada Comp. III /GenomeBC$224,543 (2006)$4,787,197 (2006‐2008)16. Downstream targets of Notch in lymphoid neoplasiaPI: A WengLLSC$52,500 (2006)$105,000 (2006‐2008)17. Downstream targets of Notch signaling in lymphoid neoplasiaPI: A WengLLSC$60,000 (2006)$180,000 (2006‐2008)18. Effects of retroelements on mammalian genesPI: D MagerCIHR$142,969 (2005)$142,969 (2006)$719,930 (2004‐2009)The goal is to focus on the development of three organs in themouse embryo, the heart, pancreas, and the liver. In particular, thefocus is on the tissues in the heart involved in valve formation andseparation of the chambers, in the pancreas on the formation ofislet cells, and in the liver on hepatocytes.The goals are to 1) characterize c‐Myc as a Notch target gene and to2) identify and characterize additional Notch target genes in apanel of established human tumour cell lines.The major goals are 1) to characterize c‐Myc as a Notch target geneand 2) to identify and characterize additional target genes in apanel of established human tumour cell lines.The goal is to understand how mobile genetic elements (“jumpingDNA”) in human and mouse genomes affect the expression andrearrangement of genes. This project will also examine the role thatmobile elements may play in determining the qualities thatdistinguish humans from our closest relative, the chimpanzee.TERRY FOX LABORATORY19. Gene therapy for sickle cell anemia and β‐thalassemia (Gene transfer and stem cell biology in sicklecell disease and supplement)Co‐PI: C Eaves, K HumphriesNHLBI/ NIHUS$437,272 (2005)US$62,290 (2006)$2,186,360 (2000‐2005)20. HOXB4 is an activator of HSC self‐renewalPI: K Humphries, G Sauvageau (UMontreal)NIH$122,962 (2005)$122,962 (2006)$416,000 (2005‐2009)21. HOXB4 target‐genes specifying hematopoietic stem cell renewalPI: K HumphriesStem Cell Network$74,899 (2005)$396,846 (2003‐2005)The goal is successful preclinical development of a gene therapyprotocol for treating patients with sickle cell disease (SCD).The goals are to 1) enhance the potential of HSCs to expand invitro, 2) develop and test clinically‐relevant strategies aimed atachieving a maximal expansion of HSCs in vitro, 3) identify aHOXB4‐containing “HSC‐renewal protein complex” and 4)determine the role of the newly identified proteins in HSC selfrenewal.This project will determine the target genes of specific transcriptionfactor is in rare cell types with the goal of identifying key transcriptsubsets that correlate with enhanced HSC self‐renewal capacity.157
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Biennial Research Report 2005 ‐200615. Dissecting gene expression networks in mammalian organogenesisCo‐PIs: P Hoodless, M MarraCo‐I: A Karsan, C Helgason, SJones, S Katz (U<strong>BC</strong>), E Levy(U<strong>BC</strong>)Genome Canada Comp. III /Genome<strong>BC</strong>$224,543 (2006)$4,787,197 (2006‐2008)16. Downstream targets of Notch in lymphoid neoplasiaPI: A WengLLSC$52,500 (2006)$105,000 (2006‐2008)17. Downstream targets of Notch signaling in lymphoid neoplasiaPI: A WengLLSC$60,000 (2006)$180,000 (2006‐2008)18. Effects of retroelements on mammalian genesPI: D MagerCIHR$142,969 (2005)$142,969 (2006)$719,930 (2004‐2009)The goal is to focus on the development of three organs in themouse embryo, the heart, pancreas, and the liver. In particular, thefocus is on the tissues in the heart involved in valve formation andseparation of the chambers, in the pancreas on the formation ofislet cells, and in the liver on hepatocytes.The goals are to 1) characterize c‐Myc as a Notch target gene and to2) identify and characterize additional Notch target genes in apanel of established human tumour cell lines.The major goals are 1) to characterize c‐Myc as a Notch target geneand 2) to identify and characterize additional target genes in apanel of established human tumour cell lines.The goal is to understand how mobile genetic elements (“jumpingDNA”) in human and mouse genomes affect the expression andrearrangement of genes. This project will also examine the role thatmobile elements may play in determining the qualities thatdistinguish humans from our closest relative, the chimpanzee.TERRY FOX LABORATORY19. Gene therapy for sickle cell anemia and β‐thalassemia (Gene transfer and stem cell biology in sicklecell disease and supplement)Co‐PI: C Eaves, K HumphriesNHLBI/ NIHUS$437,272 (2005)US$62,290 (2006)$2,186,360 (2000‐2005)20. HOXB4 is an activator of HSC self‐renewalPI: K Humphries, G Sauvageau (UMontreal)NIH$122,962 (2005)$122,962 (2006)$416,000 (2005‐2009)21. HOXB4 target‐genes specifying hematopoietic stem cell renewalPI: K HumphriesStem Cell Network$74,899 (2005)$396,846 (2003‐2005)The goal is successful preclinical development of a gene therapyprotocol for treating patients with sickle cell disease (SCD).The goals are to 1) enhance the potential of HSCs to expand invitro, 2) develop and test clinically‐relevant strategies aimed atachieving a maximal expansion of HSCs in vitro, 3) identify aHOXB4‐containing “HSC‐renewal protein complex” and 4)determine the role of the newly identified proteins in HSC selfrenewal.This project will determine the target genes of specific transcriptionfactor is in rare cell types with the goal of identifying key transcriptsubsets that correlate with enhanced HSC self‐renewal capacity.157
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