Use of T regulatory cells to induce tolerance to organ and tissue transplantation

Transplantation is the treatment of choice for many forms of end-stage organ failure and cancers of the immune system. Due to the difficulty in finding fully compatible donors, the patient’s immune system must be suppressed with drugs to prevent it from rejecting the transplanted tissue. While necessary, these drugs suppress all immune response, causing serious side effects including increased risk for infections, cancers, damage to kidneys, hypertension, diabetes and seizures. Dr. Megan Levings is looking for a way to protect the transplanted tissue without compromising other aspects of the normal immune response. She is studying a novel class of white blood cells, known as T regulatory (Tr) cells, which are thought to have the ability to selectively suppress immune responses. Dr. Levings is exploring the molecular and cellular biology of Tr cells to better understand how they develop and act to induce an immune response. Potentially, these cells might be the basis for a more directed approach to controlling rejection.

Investigation of pathways underlying retinal degeneration

Retinitis pigmentosa (RP) is a form of inherited blindness that results from the death of light-detecting neurons called rod cells. It is usually diagnosed in children, adolescents and young adults and typically begins with night blindness followed by progressive deterioration of peripheral vision (tunnel vision). Dr. Orson Moritz is studying transgenic frogs with the same genetic mutations that cause the condition in humans. His goal is to identify the biochemical pathways that are activated by these mutations and lead to the death of rod cells. To confirm the involvement of these pathways, he is studying transgenic frogs in which these pathways are disrupted to determine whether this prevents development of RP. The research could enable design of therapies to prevent the progression of RP in humans.

Improving psychosocial treatment adherence in young individuals presenting with a first psychotic episode

Research has shown that psychosocial treatments, such as cognitive-behavioural therapy, can reduce symptoms and improve overall well-being of people who are experiencing a first psychotic episode. Yet, studies also show that only about one-third of potential candidates for treatment agree to participate in and complete the therapy. Dr. Tania Lecomte is exploring why some individuals experiencing a first psychotic episode refuse or fail to adhere to treatment. Besides assessing whether or not motivation enhancement therapy improves adherence to treatment, she is also evaluating the impact on symptoms and patient well-being when they receive both motivation therapy and cognitive-behavioural therapy, or just the latter. If motivation therapy is shown to be effective, results from the study could help young people cope better with psychotic symptoms. Her research may also reveal new information about factors that motivate individuals with psychotic symptoms to seek help.

Retinoids in synovial sarcoma

Synovial sarcoma is a form of cancer occurring most commonly in the limbs of young adults. Patients are treated with aggressive surgery and radiation, but the disease often spreads and proves fatal. Current chemotherapy provides limited benefit, with serious side effects. Using gene microarrays, a new technology that allows scientists to monitor tens of thousands of genes simultaneously in tumour specimens, Dr. Nielsen helped discover a group of genes playing a central role in synovial sarcoma. These include several potential therapeutic targets, including the signalling pathway involving retinoic acid, a vitamin A derivative. Several existing and experimental drugs interfere with this pathway and have been successfully used to treat other cancers such as leukemia, but have not been tested in synovial sarcoma. Dr. Torsten Nielsen is using the gene expression profile of this cancer type to develop targeted therapies needed for its treatment.

Physical activity as primary prevention: evaluating novel interventions for child health

Physical activity can help prevent a host of chronic diseases, including osteoporosis and obesity, two major medical conditions that likely begin with childhood inactivity. But it’s estimated that three out of five Canadian youths between five and 17 years of age are not physically active enough to ensure optimal growth and development. Weight reduction programs targeting children who are already obese have largely been unsuccessful, which indicates the need for a stronger focus on developing more effective prevention strategies. Several studies have shown that school-based programs can effectively improve bone health. Dr. Heather McKay is evaluating the impact of innovative physical activity programs on bone health and weight of elementary school children, research that could lead to the development and implementation of public health programs to encourage physical activity and improve the health of Canadian children.

Regulation of thyroid hormone-dependent apoptosis and proliferation by the ING tumour suppressor

Thyroid hormones are critical for proper growth and development and are equally important in maintaining good health. Research has shown that these hormones play a key role in regulatory pathways that ensure cells act appropriately when signaled to grow, divide or undergo apoptosis (programmed cell death). Many molecules are involved in these pathways including proteins that are known to contribute to cancer progression. Dr. Caren Helbing is investigating the relationship between ING protein (a growth inhibitor) and thyroid hormones. ING’s tumour-suppressing action is reduced in many cancers, including a subset of breast cancers. Dr. Helbing is exploring how ING may be involved in regulating the way a cell responds to thyroid hormones. Clarifying the relationship between ING and thyroid hormones, may provide new insight into the ways cancer cells bypass normal cellular controls that normally would cause their destruction.

Intrinsic capacity of spinal circuits for restoration of motor coordination after neurotrauma

While the brain is the body’s command centre, connections within the spinal cord control rhythmic activities like walking. The brain contributes to such movements, but spinal cord circuits can coordinate muscle activity on their own, relying on feedback from moving limbs to regulate the pattern. When these connections are lost or altered due to injury to the brain or spinal cord, movement in the arms and legs may be greatly reduced depending on the location and severity of the injury. Dr. Paul Zehr’s research focuses on improving understanding of how coordinated muscle activity in arms and legs can be improved after neurotrauma. He is working with individuals who have had strokes or spinal cord injuries to determine the extent to which enhanced sensory feedback techniques can retrain spinal cord circuits and improve limb coordination. New knowledge gained from this research may lead to more effective methods of improving motor coordination following brain or spinal cord injury.

Development of a leisure time walking program based on the theory of planned behaviour stage 1: belief elicitation and evaluation

Substantial evidence associates physical inactivity with the development of several chronic diseases and premature mortality. Conversely, extensive research indicates physical activity helps prevent cardiovascular disease, obesity, stroke, diabetes, cancer, osteoporosis and other conditions. Despite this information, about 57% of adult Canadians do not meet the minimal requirements for physical activity, and half of those who begin a regular physical regimen drop the activity within six months. The overwhelming majority of Canadians — more than 70% — choose walking as their preferred physical activity during leisure time. Dr. Ryan Rhodes is studying beliefs about leisure time walking. The research includes an initial study assessing physical activity beliefs and a second survey assessing actual time spent walking. Results from the research will be used to develop a provincial leisure time walking campaign for adults. Dr. Rhodes’ ultimate goal: developing effective campaigns for promoting physical activity in specific populations, such as middle-aged adults and older adults.

Animal Determinants of Emerging Infectious Disease

This unit’s goal is to improve understanding and ability to address the emergence of infectious diseases such as West Nile virus that are passed to humans by interaction with an animal host (such as mosquitos in the case of West Nile). The unit will focus on gathering sound evidence of the origins of such diseases in animal/environmental systems as a basis for developing effective, evidence-based disease prevention and control plans.

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Cancer Control Research Unit

This unit combines the skills and talents of researchers in the BC Cancer Agency’s Cancer Control Research Program and Canada’s Michael Smith Genome Sciences Centre to create a critical mass of expertise in cancer epidemiology, environmental exposure assessment, genetics and biostatistics. The unit will explore the interaction between environmental toxins and genetic susceptibility in determining cancer risk, focusing on environmental, genetic and gene-environment studies in non-Hodgkin’s lymphoma, skin cancer, ovarian cancer and cancers of the mouth.

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