Terry Fox Laboratory

2003 Research Unit Award

The overall goal of this unit is to make breakthroughs in the prevention, early diagnosis and treatment of cancer by focusing on the role and therapeutic promise of stem cells. Studies will focus on defining molecular pathways that govern stem cell renewal, viability, their development into specific types of cells (such as bone and blood) and their ability to multiply in a variety of body tissue. Researchers are particularly interested in understanding how inherited and acquired gene mutations may influence these processes and contribute to the development of cancer.

Since its establishment in 1981, the Terry Fox Laboratory at the BC Cancer Agency has developed an international reputation for research exploring the molecular mechanisms and pathways involved in the regulation of cell renewal systems. The laboratory will apply MSFHR unit funding to a major new initiative centred on the functional genomics of stem cells, the precursor cells from which all cell types develop. The unit’s overall goal is to make breakthroughs in the prevention, early diagnosis and treatment of cancer through research:

• To define molecular pathways that govern normal stem cell self-renewal, viability, lineage choice and proliferation.
• To determine if and how these pathways are regulated by external cues.
• To discover and validate specific changes that contribute to the expression and progression of a transformed phenotype that leads to disease.

Recent advances in technologies for genomics (the study of genes and their function) and proteomics (the study of proteins and their function), in combination with new gene manipulation, cell analysis and cell sorting capacity, have provided powerful new tools for research into the molecular basis of normal and malignant stem cell regulation. New information from such research will make it possible to discern key events (patterns of gene and protein expression) that give rise to specific biological responses of stem cells in normal and disease states. These in turn will present useful targets for disease correction or therapeutic interventions. Within this overall framework of investigation, researchers in the Terry Fox Laboratory will target their efforts in four areas:

• Signaling Pathways Controlling Stem Cell Renewal, Differentiation and Development
  The intracellular pathways and signals that regulate stem cell self-renewal and differentiation into specific cell types are poorly understood. The Terry Fox Laboratory brings collective expertise in the biology, manipulation and signaling of hematopoietic (blood and immune) stem cells to the task, with the goal of developing new knowledge that will enhance the ability to use stem cells in the treatment of cancer and other diseases.
• Genome Instability, Telemere Biology and Sensescence
  Studies will focus in two areas: The first is the action and potential for retroelements, which make up at least 40 per cent of DNA, to cause genomic instability and abnormal patterns of gene expression, and the degree to which this may be affected by age or malignant transformations. A second focus is on clarifying certain molecular mechanisms that have evolved in long-lived mammals to control unlimited and life-threatening cancerous proliferation of tissue-specific stem cells and lymphocytes.
• Stem Cell Plasticity, Tissue Genesis and New Therapeutics
  Developing new knowledge about and new models for testing therapeutic applications of: (1) the molecular mechanisms that determine how the lineage potentialities of cells with stem cell properties are established (i.e. determine how a stem cell is activated to begin multiplying as a particular cell type); (2) the molecular regulators that maintain such cells in (or release them from) an undifferentiated state.
• Novel Approaches to Stem Cell Expansion
  Hematapoietic stem cells are used for a variety of transplantation therapies but the length of time required for such cells to differentiate sufficiently to restore normal blood and immune function causes serious, and in some cases, fatal side effects. Researchers will explore the genes and molecular pathways that regulate both the proliferation and maintenance of stem cells in their multi-potential but “uncommitted” state, with the goal of finding new approaches to stimulating large scale expansion of hematopoietic stem cells in the laboratory to improve transplantation outcomes.

Completed award term September 2009.

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