Research Location: Terry Fox Laboratory

Natural Killer (NK) cells are immune cells with an important role in the first line of defense against cancer formation, metastases (spread) of tumour cells, and infections by viruses and other pathogens. Once known solely for their role in the innate immune system, responding to pathogens in an immediate and non-specific way, research now suggests that certain NK cells might also be involved in regulating the more targeted adaptive immune response. It is believed that a subset of NK cells in the lymph node is largely responsible for this function. With new knowledge about subsets of NK cells that have specialized functions, researchers are now looking at how these NK cells arise. It is possible that in addition to the NK cells that develop in bone marrow, other immature NK cells travel to different parts of the body where they mature in specific microenvironments that affect their function. In the lung this could mean a better NK cell response to cancer metastases or virus infection, whereas lymph node NK cells might be better at interacting with other immune system components. Timotheus Halim’s research seeks to find immature NK cells (NK cell progenitors) in sites other than the bone marrow. NK cell progenitors have already been found in the lymph node and lung. Now, Halim is using different mouse models to evaluate how important these progenitors are in forming mature NK cells. He is also determining if the NK cells that arise from these novel NK cell progenitors have specialized functions. A better understanding of NK cell development and function is critical in understanding the overall management of the immune system. Ultimately, this knowledge could help in the development of immunotherapy and other forms of treatment against cancer and infection.

Human embryonic stem cells (ES cells) — cells obtained from an embryo when they are only a few days old — are unique because they can become any type of cell. They can also multiply in the laboratory for very long periods of time without losing this special ability. ES cells offer huge medical potential, both in research and clinical applications. They could, for example, be turned into cells affected by cancers, such as blood cells or brain cells, then genetically altered to become cancer-like and studied to identify potential drug targets or other unique characteristics. Human ES cells could also be used as a cell source for many different kinds of transplantation. One of the biggest hurdles to overcome in working with human ES cells is increasing understanding of how these cells turn into specific kinds of cells. Because they can become anything, ES cells often become many different things at once, which makes them difficult to study and potentially inappropriate for transplantation. A better understanding of the mechanisms an ES cell uses to turn into different kinds of cells would help ES cell differentiation be better controlled and directed towards cell types of interest. Building on her previous MSFHR-funded research, Melanie Kardel is researching how ES cells turn into blood cells. Kardel’s focus is on determining how many blood cells can be produced from a single ES cell, and what genes can influence either the number of blood cells produced or how long it takes to produce them. The research could contribute to more standard, controlled procedures for high efficiency blood cell production from human ES cells.

Leukemia affects one to two per cent of the population in the industrialized world. The disease occurs when the genes that control the normal process of blood cell formation function abnormally, and bone marrow produces malignant white blood cells as a result. These cancerous cells accumulate, interfere with the body’s production of healthy blood cells, and make the body unable to protect itself against infections. A family of genes called Hox genes are present in elevated levels in patients with some forms of leukemia, and are known to play a crucial role in the disease. Dr. Koichi Hirose is investigating the molecular function of these genes to explain how they transform normal blood cell development into leukemia. His research could help in the development of new therapies for treating Hox-related leukemia.

Antigens are foreign substances that stimulate an immune response. While immune responses to protein antigens have been extensively studied, little is known about the way carbohydrate antigens stimulate the immune system. Carbohydrates in the outer layer of bacteria, called capsular polysaccharides (CPS), protect bacteria. Most bacteria that cause serious infections in humans have this characteristic. Dr. Motoi Maeda hopes to induce an immune response to CPS to prevent many diseases caused by bacterial infection. He has found that the CPS in two common strains of bacteria stimulates white blood cells called natural killer T cells (NKT). Motoi believes NKT cells are critical for initiating an immune response to disease-causing bacteria that have capsules for protection, and is researching how they are stimulated. This information could be used to create new vaccines against common infectious bacteria.