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.
Program: Scholar
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.
Functional analysis of the CD34-related molecule, MEP21, in adhesion and stem cell differentiation
Once organisms are fully developed, stem cells are the basis for replenishing cells that wear out or are otherwise destroyed in the normal course of living. Researchers are now looking for ways of identifying and manipulating stem cells to regenerate organs or tissues such as heart muscle, liver, brain or the surface of the lung and digestive tract that have degenerated due to disease. The most well studied stem cells to date, are hematopoietic stem cells, which are produced in the bone marrow and are the precursors from which all blood cells develop. Dr. Kelly McNagny’s laboratory discovered MEP21, a molecule that appears to have a close connection to stem cells since its activation correlates closely with the appearance of stem cells in tissues. This suggests that the molecule may be involved in stem cell production and the processes by which stem cells grow differentially to become a specific type of tissue. Dr. McNagny’s research has shown that MEP21 is required for survival – i.e., mice lacking the molecule die shortly after birth. He is now studying its role in activating adult stem cells, with the goal of finding new ways of purifying and using stem cells to regenerate tissues.
Appropriate uses of genetic information in the diagnosis, treatment and prevention of autosomal dominant polycystic kidney disease and rheumatoid arthritis
Genetic testing confirms the presence or absence of genes associated with the development of various diseases. Early detection of these genes sometimes enables physicians to recommend interventions that can help to delay onset of disease or prevent the most serious symptoms. The downside, however, is that many of the diseases that are detectable through genetic testing have no treatments or cures. This creates serious ethical and other considerations about when and how such tests should be administered. Dr. Susan Cox is studying the potential benefits and harms of using genetic information to diagnose, treat and prevent two common and devastating chronic diseases: autosomal dominant polycystic kidney disease (ADPKD) and rheumatoid arthritis (RA). Increased availability of genetic screening for ADPKD may have implications for routine screening of people at risk for the disease and for assessing potential kidney donors. The discovery of a gene influencing the severity of some forms of RA may prove to be clinically useful in tailoring drug therapies to persons diagnosed with the condition. Dr. Cox is documenting and comparing perspectives on these developments from patients, families, health care professionals and non-profit agencies. She will use this information to develop criteria for the appropriate use of genetic information in the diagnosis, treatment and prevention of ADPKD and RA. Results from the study will also be relevant to other genetic and hereditary diseases.
Cell therapies for the treatment of hematopoietic malignancies
Though small in numbers, stem cells are responsible for the continued production of blood cells throughout a person’s life. They are also responsible for regenerating the blood-forming system following a bone marrow transplant in people with leukemia and other blood diseases. While blood stem cell transplantation is a promising therapy, its use is currently restricted because researchers have not yet found a way to reproduce these cells in large enough numbers for effective transplantation. Dr. Clayton Smith’s research is devoted to developing a better understanding of blood-forming stem cells so they can be effectively isolated and manipulated. Using leading-edge bioengineering and computer-based technologies, he is systematically exploring how the body’s environment affects stem cell growth, to see if these conditions can be replicated outside the body. He is also studying the function of certain genes that may be important to stem cell growth. Ultimately, he hopes to learn enough about stem cells to be able to grow them in large numbers outside the body for use in blood stem cell transplantation.
The demand for hereditary cancer services
The Hereditary Cancer Program at the BC Cancer Agency provides genetic testing and counseling services. The demand for these services in BC depends on many factors, each of which is subject to change. Factors include the growing knowledge in basic, applied and social sciences relating to hereditary cancer; the size of BC’s population and its characteristics in terms of age, ethnicity and family size; the evolving criteria by which people are deemed eligible for services; and people’s desire for these services. Through his research, Dr. Chris Bajdik is determining the demand for hereditary cancer services in BC and predicting how this demand may change in the future. He has created a computerized simulation model of the BC population, based on information about demography, cancer epidemiology and etiology, genetics, genetic technology, and human behaviour. The results from this model will help the BC Cancer Agency plan its services and assess the health benefits and costs of its Hereditary Cancer Program.
Structural analysis of the bacterial Sec-dependent protein secretion system
Cells have compartments separated by membranes. Many proteins are made in one compartment but actually function in another. The ability of proteins to travel across membranes within cells is essential to cell life. Malfunctions in this process can lead to a variety of inherited and autoimmune diseases in humans. Dr. Mark Paetzel’s research focuses on the mechanisms by which proteins travel across cell membranes, a process called protein targeting and translocation. Using the technique of X-ray crystallography, Dr. Paetzel is uncovering the three-dimensional structures of the protein complexes that make up the molecular machines involved in bacterial protein targeting and translocation. A better understanding of the functions and mechanisms of these protein complexes may yield insights about how the process works in human cells. In addition, learning how the process differs between bacteria and human cells could lead to a novel class of antibiotics that can shut down protein targeting and translocation activities in bacteria, but leaves human cells unaffected.