Terry Fox Laboratory - BC Cancer Agency

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