Terry Fox Laboratory - BC Cancer Agency

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British Columbia Cancer AgencyTERRY FOX LABORATORY22. Integrated linked kinase as a therapeutic target in acute myeloid leukemiaPIs: D HoggeLLSC$50,000 (2005)$50,000 (2006)$150,000 (2006‐2008)We will test the possibility that abnormal activation of anintracellular signaling molecule, integrin linked kinase or ILK, iscritical to the survival of AML cells including those malignant‘stem cells’ that allow long‐term growth leukemia in mice and thatinhibition of ILK will result in the death of AML cells whilesparing most normal cells.23. Investigation of the roles of new genes selectively expressed in primitive human mammaryepithelial cellsPI: C EavesCBCF BC/Yukon Chapter$50,000 (2006)$150,000 (2006‐2008)The goals are to compare the expression of certain genes inprimitive normal human mammary cells their mature progeny, tofollow these changes during the differentiation of the primitivecells in cultures and to test how they may regulate this process.24. Manipulation of proliferative abnormalities in acute myeloid leukemia (AML) stem cellsPI: D HoggeCancer Research Society$57,000 (2005)$114,000 (2003‐2005)The goal is to characterize the molecular basis of proliferativeabnormalities in AML cells in order to facilitate the identificationof targets for novel therapeutic agents.25. Modeling transcriptional networks during cardiac cushion developmentPI: A KarsanCo‐PI: P HoodlessCIHR$10,000 (2005) to PH.$2,391,13 (2005‐2010)The overarching objective of this program is to elucidate thetranscriptional program of this critical region of the heart (theendocardial cushions) in human tissues, and generate andvalidate a detailed model of this developmental process.26. Molecular characterization of AHI‐1, a novel signaling molecule with a SH3 and multiple WD40‐repeat domains, in normal and leukemic hematopoiesisPI: X JiangMSFHR Estab. Grant$75,000 (2005)$75,000 (2006)$225,000 (2005‐2007)The goal is to characterize the functions of Ahi‐1 in regulatingnormal hematopoietic stem cell proliferation and differentiationusing a conditional knockout model system, and to identify andcharacterize molecular partners involved in normal and alteredsignaling pathways regulated by Ahi‐1 using a new proteomicsapproach (IP+MS).27. Molecular biology of the initiation of T‐cell transformation by RasGRP1 and Ras GTPasesPI: R KayCancer Research Society$60,000 (2005)$60,000 (2006)$240,000 (2004‐2008)This project will use a murine model to investigate mechanisticlinks between normal and malignant development of T‐cells and toidentify activating mutations in Ras GTPases that frequently occurin T‐cell acute lymphoblastic leukemia28. NK and NKT in Herpes simplex virus Type 1 (HSV 1) infection in micePI: L Kastrukoff (UBC)Co‐PI: F TakeiCIHR$78,720 (2005)$78,720 (2006)$393,600 (2005‐2008)Resistance to Herpes simplex virus (HSV) infection, which causesmultiple sclerosis‐like syndrome in mice, is regulated by a genecluster encoding multiple receptors on natural killer (NK) cells.The goal of this project is to determine the role of NK cells inimmune response to Herpes simplex virus and to identify thegenes and the receptors responsible for the resistance to HSVinfection.158
Biennial Research Report 2005 ‐200629. NK cell differentiationPI: F TakeiCIHR$128,027 (2005)$128,027 (2006) $320,068(2003‐2007)30. Normal and leukemic hematopoiesisPI: K HumphriesCo‐Is: C Eaves, P Hoodless,Krystal, P LansdorpNCIC Group Grant$5,238,379 (2002‐2007)GThe goal of this study is to compare the generation of NK cellsfrom primitive blood‐forming cells in newborn and adult mice todetermine why this process takes a long time.The overall goal of this program is to determine how normal bloodcells become leukemia cells and to apply that information todevelop new leukemia treatments.This program is comprised of the following sub‐projects:TERRY FOX LABORATORY31. Notch signaling in lymphoid neoplasiaPI: A WengMSFHR Estab. Grant & CareerDev. Award$62,500 (2006)$377,500 (2006‐2011)32. Notch signaling in lymphoid neoplasiaPI: A WengNCI Career Development AwardCharacterization and self‐renewal control of normalhematopoietic stem cellsPI: C Eaves $191,400 (2005) $191,400 (2006)The long‐term goal of this project is to develop methods forcontrolling and manipulating normal hematopoietic stem cell(HSC) expansion.Genetic determinants of hematopoietic stem cell functionPI: K Humphries $171,535 (2005) $171,535 (2006)The major goals of this project are to discover and elucidate theroles/mechanisms of novel Hox and related molecules in normaland leukemic hemopoiesis.Regulation of proliferation vs differentiation during normal andleukemic hemopoiesis.PI: G Krystal $127,045 (2005) $126,166 (2006)The major goals of this project are to understand the effects of theTFGβ and PI3K pathways on normal and abnormal hemopoieticcells.Telomere length regulation in murine cellsPI: P Lansdorp $173,585 (2005) $175,610 (2006)The goal of this project is to understand telomere lengthregulation in the mouse and clarify the relation between telomerelength and telomere function.TGFβ signal transduction pathways in developmental programsPI: P Hoodless $149,250 (2005) $149,250 (2006)This project examined the role of the transcriptional repressor,TGIF, in embryogenesis, cell cycle and signaling in the mouse.The major goals are to characterize Notch target genes inestablished human tumour cell lines, and to score these targetgenes for leukemogenic potential in animal models; also, tocharacterize promoter elements upstream of candidate Notchtarget genes.For project description see Pathology and Laboratory Medicine.159
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Terry Fox Laboratory - BC Cancer Agency

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