Heart function is regulated in large part in the upper right hand corner of the heart, where a cluster of pacemaker node cells generate the pulsatile electrical signals that spread throughout the heart muscle. These signals cause the heart to rhythmically contract and relax, leading to the smooth flowing of blood through the circulatory system. In order to send pulsatile signals and coordinate the heartâs activity, pacemaker node cells possess a unique collection of proteins. This includes ion channels, that selectively permit charged ions to cross the membrane barrier surrounding cells, generating an electric field that can be spread to surrounding cells. A distinguishing feature of the pacemaker is that it spontaneously generates these electrical impulses. Specific ion channel proteins, called HCN channels, are largely responsible for this spontaneous activity. But how and why HCN channels express as they do in these pacemaker cells is largely a mystery. Christian Peters is exploring how the functioning, or even the presence of these proteins, is affected by their interactions with accessory proteins on the interior of the cell. By developing an understanding of these interactions, his research will contribute to our knowledge of the workings of a healthy heart, and contribute to the prevention or cure of ailments associated with a malfunctioning of the myocardium, the muscular tissue of the heart.
Program: Trainee
Developing innovative nanopharmaceuticals for the treatment of relapsed breast cancer
Therapeutic antibodies are a popular and effective class of cancer drugs, particularly when combined with more traditional treatments. While natural antibodies are found in our blood all the time, they do not recognize cancer. Therapeutic antibodies are designed to recognize special molecules found only on the surface of cancer cells, allowing them to target and kill those cells without harming healthy ones. This results in a dramatic decrease in the side effects of chemotherapy such as nausea, fatigue and hair loss. Little is known about how therapeutic antibodies work, including the reasons why they are ineffective in some cancer patients. This lack of knowledge currently makes it hard to adapt or improve the drugs. Jesse Popov is studying trastuzumab, a therapeutic antibody used to treat aggressive breast cancers. Focusing on revolutionary new theories about the way that cellular membranes function, Jesse is working to determine how trastuzumab works in the body, as well as the basis for trastuzumab resistance. With new insights, he hopes to uncover ways to tailor therapeutic antibody-containing pharmaceuticals to make them more effective in treating different forms of cancer. This research is part of the ongoing Breast Cancer Research Program at the BC Cancer Research Centre, an initiative focused on identifying pharmaceutically viable methods for improving the effectiveness of breast cancer treatment.
Role of Amyloid in Failure of Transplanted Human Islets
In Type 1 diabetes, beta cells are destroyed by the immune system, leaving the body unable to produce insulin. Type 1 diabetic patients inject insulin several times a day to normalize their blood glucose levels. Estimating the correct dose of insulin to administer is difficult: too much insulin leads to hypoglycemic shock, while chronic hyperglycemia (a shortage of insulin) can lead to organ damage and related complications such as blindness, kidney failure, neuropathies, vascular damage and pain in the limbs. The transplantation into diabetics of insulin-producing islet cells shows promise for relief from daily insulin injections and the development of diabetic complications. However, islet transplantation is in the early stages, and long-term rates of transplanted islet graft survival and maintained function are low: only 10 per cent of islet transplanted recipients remained free from insulin injections five years post-transplantation. Kathryn Potter is working to better understand the mechanisms underlying graft failure. In particular, she is interested in how stressors unrelated to immunityâsuch as pre-transplant and post-transplant hyperglycemia and the use of immunosuppressantsâmay cause dysfunction in transplanted beta cells and lead to graft failure. Her research may lead to modifications to current transplantation protocols that improve long-term islet transplantation success rates.
Accelerated telomere shortening in women with breast cancer: The buffering effect of social support against physiological stress markers
Psychological stress has been frequently implicated in disease development and progression, but the determinants of this relationship remain unclear. A recent finding has demonstrated that chronic and perceived stress affects health by influencing the rate of cellular aging. The literature also shows that social support buffers against stress. Jillian Satin is exploring the relationship among stress, social support and cellular aging in women who have been diagnosed with breast cancer. While chronological age is usually used as a predictor of age-related disease, cellular aging may be a more accurate predictor of onset and a potential route of disease prevention. Jillianâs research is examining whether social support modulates the relationship between objective stressful life events and cellular aging. Since social support has been shown to decrease perceived stress, Jillianâs hypothesis is that social support decreases the accelerated rate of cellular aging. If this hypothesis is correct, it would suggest that social support interventions should be made available to those at risk and should be integrated into the health care that women with cancer receive. Although this study focuses on breast cancer, the findings could prompt further exploration into treatment of cancer and age-related diseases.
Who has Epilepsy in British Columbia?
According to national surveys, an estimated 30 per cent of Canadian children between six and 18 years of age suffer from chronic conditions and/or disabilities, including seizure disorders. However, these surveys do not allow for provincial analysis, due to small sample sizes, and there is limited comparability between surveys because of differences in target groups, methodologies and conceptual frameworks. Currently, there are no comprehensive prevalence data on children with special health care needs in BC, such as children with epileptic seizures, who account for half the visits to specialists because of neurological disease. Veronica Schiariti is researching the influences of neighbourhood income, population density, health care availability and community resources on the treatment prevalence of epilepsy in BC children under the age of 19. She is examining both diagnosis and treatment patterns of pediatric patients with epilepsy. Veronica hopes that her research will contribute to improved treatment for epileptic children by identifying disparities in health service delivery, informing health care policy decisions, and enabling long-term tracking and study of health and development outcomes at the individual level and in the broader population.
Genetic Variation in Apoptotic Genes and Susceptibility to Non-Hodgkin Lymphoma
Non-Hodgkin’s Lymphoma (NHL) is a cancer of lymphocytes â a type of white blood cell that moves throughout the body as part of its role in immune defense. As a complex disease with both environmental and genetic factors contributing to its development, NHL is incurable and the fourth highest cause of cancer deaths in Canada. Johanna Schinas aims to identify the genetic factors contributing to NHL susceptibility. She is focusing on the role of apoptosis which is a natural process of cell death triggered by genes and carried out by the immune system. When an immune cell originally meant for destruction escapes apoptosis, it becomes an ideal environment for further changes that can cause progression to malignant cancer. By searching for DNA variants in apoptosis genes that are associated with the development of lymphoma, she hopes to identify markers of genetic susceptibility to lymphoma. This will lead to not only a better understanding of the molecular basis of this cancer, but also assist in the design of effective surveillance programs for at-risk individuals.
Optimizing the Role Nurses Play in Preventing Pediatric Deaths: An Application of Situational Awareness
Up to 23,000 preventable deaths are estimated to occur each year in Canadian hospitals. Nurses who provide care at the bedside are well positioned to promote patient safety, because a critical component of their role is to notice and gauge potential risks. Although research suggests that nursesâ workload, training and experience influence patient mortality, little is known about the actual processes that nurses use to prevent or reduce error. Kim Shearer is applying the model of âSituational Awarenessâ (SA) to study pediatric nurses performing resuscitation of children in hospital. SA â defined as knowing what is going on in your environment â has been proposed as the primary basis for decision-making and performance in complex, dynamic systems, helping researchers understand how threats within the environment are gauged and safety is facilitated. Kimâs study will identify factors that promote or impede nursesâ ability to gauge the work environment and make decisions, generating the basic knowledge needed to create computer simulations for teaching and testing SA in pediatric resuscitation. Findings of this research will help to prevent or minimize error and enable development of novel health education interventions to improve SA and hence the safety of children in dynamic and complex acute care environments.
Quantitative Single Cell Proteomics for Stem Cell Analysis in Microfluidic Devices
Stem cells are defined by their unique capabilities to either replicate (self-renew) or differentiate into more specialized cell types such as nerve cells (neurons), immune cells and skin cells. If health researchers could controllably direct stem cells to differentiate into particular cell types, stem cells could potentially be used as clinical therapeutics for a diverse range of diseases, including neurodegenerative diseases, autoimmune disorders, heart and liver disease, and cancer. Presently, the control of stem cell differentiation is hampered because researchers lack the necessary knowledge and tools for studying the molecular pathways that guide stem cell differentiation into specific cell types. Anupam Singhalâs research seeks to harness recent advances in micron-sized fluid-handling devices and nanotechnology in order to quantitatively study stem cells at the single cell level. In particular, he will propose a general platform for performing rapid and high-throughput quantification of multiple proteins in single stem cells. This strategy should help to identify proteins (e.g. transcription factors for gene expression, secreted proteins) that influence the stem cell fate decision. This information will then be used to construct model molecular pathways that guide stem cell differentiation, a critical milestone that must be reached before stem cells will find widespread clinical applications.
Phenotypic Rescue of Neuronal Structure and Function in a Rett Syndrome Mouse Model
Rett syndrome is a debilitating neurodevelopmental disorder that affects between one in 10,000 to one in 15,000 females. Symptoms that appear in early childhood include severe mental disabilities, impaired speech and movement, and seizures. Individuals with Rett syndrome show abnormalities in the size and structure of certain neurons in the brain. At present, there is very little treatment available for this disease. In most patients, Rett syndrome is caused by mutations in a single gene called MECP2. David Stussâ research is part of a collaborative effort that is investigating methods for introducing a functional form of this gene into the brain at the appropriate developmental stage. This is expected to allow neurons to follow their normal course of growth and maturation. The methods being developed use engineered lentivirus vectors that are capable of delivering genetic material into differentiated, non-dividing cells like neurons. These viral vectors can also introduce genes for fluorescent proteins into targeted cells at the same time, allowing detailed microscopic visualization of the effects of treatment on neuronal structure. If the rescue of neuronal structure and brain development following therapeutic gene transfer can be demonstrated, this research will be an important first step in creating a therapeutic strategy for treating the devastating effects of Rett syndrome in children.
Mechanisms of calcium waves and their contribution to vasomotion in the cerebral circulation
Calcium that is released from one part of a smooth muscle cell can sometimes travel along the length of the same cell in a wave-like manner. This phenomenon is known as a calcium wave. Under certain conditions, a calcium wave can synchronize with other calcium waves from neighbouring cells to cause rhythmic contractions of blood vessels, known as vasomotion. Why vasomotion occurs is not completely understood, but it may be important in controlling blood flow in small diameter blood vessels, such as the cerebral arteries in the brain. Cerebral arteries regulate the flow of blood to working areas of the brain, but this flow is compromised during conditions such as stroke, hypertension or diabetes. There is evidence that the frequency of vasomotion is affected in these conditions. Harley Syyong is studying vasomotion and its underlying mechanisms. Using both molecular and ultrastructural methods, he is exploring the contribution of calcium waves to vasomotion. This research will explore how calcium waves are generated, their role in vasomotion and how the physical structure of the cell supports their propagation. This project is laying the groundwork for future studies to examine how the underlying mechanisms of vasomotion are affected during pathological conditions such as stroke, hypertension and diabetes. Ultimately, this may lead to new drug therapies for treatment of these conditions.