Many types of rare inherited genetic disorders profoundly affect children and their families. While disorders like Anderson syndrome, Bartter's syndrome, and DEND (Diabetes with Epilepsy and Neuromuscular Defects) affect different organ systems and manifest with different symptoms, these diseases are all caused by genetic mutations in the KIR family of proteins. Mutations in KIR proteins can also be involved in less severe symptoms, including cardiac arrhythmias and vascular defects. The KIR proteins are a family of ion channels known as inwardly rectifying potassium channels. These ion channel proteins form pores in cell membranes, which can be switched on or off, by opening or closing “gates” in the ion-conducting pore. When the gates are open, charged ions can pass across the membrane, generating electrical currents and influencing the membrane voltage. These KIR proteins regulate a diverse set of processes, from beating of the heart to hormone release from the pancreas, and can be influenced by a number of cellular processes and molecules.
Dr. Harley Kurata’s work is focused on the KATP channel, which is a member of the KIR family and is regulated by the “fuel” (ATP) that drives all cells. The KATP channel can sense the metabolic state of cells and serves as a critical trigger for insulin release from pancreatic beta-cells. KATP channel mutations are now recognized as an important cause of genetically inherited insulin disorders, ranging from diabetes (too little insulin released) to hyperinsulinism (too much insulin). Dr. Kurata's team hopes that by identifying the specific mutations involved in KATP, therapeutic approaches to both diseases can be developed. KATP channels are also present in the heart, and although their role in cardiovascular function remains enigmatic and controversial, further investigation of this unique set of proteins has the potential to impact other diseases.
Pre-term babies, those born before week 37 weeks of gestation, are more susceptible to invasive infections than full-term babies. The smallest babies born “extremely” premature (those born before 32 weeks, or approximately 1,500 grams or less of birth weight) suffer the greatest burden of infection among all age patient age groups in BC and other developed countries in general. About one in four “extremely” pre-term babies suffers from an invasive infection, which adds up to more than 8,760 new invasive infections in North America each year. In addition to the immediate health risks, such as a major loss of cardiorespiratory function or death, these infections may lead to long-term physical and intellectual handicaps in these children.
The work of Dr. Pascal Lavoie aims to understand why pre-term babies are so vulnerable to infections caused by common micro-organisms. Dr. Lavoie and his team are examining the way that babies’ immune cells work early in life to determine if this differs from the function of mature immune systems. In order to do this in a way that is completely safe to babies, he takes advantage of scavenged blood samples (he uses, for example, placental blood normally discarded at birth) analyzed using sophisticated technologies to extract detailed information about the human immune system.
Dr. Lavoie also aims to understand why the immune system of pre-term babies appears underdeveloped and what impact therapeutic manipulation of the latter may have on diseases such as bronchopulmonary dysplasia: a chronic form of neonatal inflammatory lung disease which appears to be caused by excessive activation of the immune system during infection. Ultimately, Dr. Lavoie hopes that a better understanding of the immune systems of pre-term infants will help researchers and doctors develop better treatments to boost immune defenses and prevent the dreadful consequences of infections in vulnerable newborns.
Arthritis consists of more than 100 types of conditions and is the most common cause of severe chronic pain and disability in Canada, affecting 4.4 million Canadians. While effective treatments are available, they are not consistently prescribed by health professionals or used by patients. Currently, researchers and research funding agencies have focused on tailoring research findings to specific audiences via methods such as plain language summaries, education sessions, public symposia, and media events. However, the impact of this information can be limited if it is provided at a different time and place than when people need to use it. Digital media offer a range of applications – social networking tools, interactive games, animation, and video/audio recordings – that provide tremendous flexibility for delivering “just-in-time” information when and where it is needed by the user. The depth, richness, and accessibility of this information are infinitely greater when conveyed via digital media than the current methods of publishing research results.
The goal of Dr. Linda Li's research program is to optimize the health of Canadians with arthritis by studying how people make treatment decisions and by improving the use of effective treatments using innovative digital media tools. Her program focuses in three areas: 1) understanding how patients with arthritis make treatment decisions; 2) evaluating models for health professionals who provide arthritis care; and 3) developing digital media interventions and evaluating their effectiveness to improve clinical practice, treatment decisions, and patient health.
This research program focuses on improving the health outcomes of people with arthritis by harnessing the engaging power of digital media to deliver research knowledge when and where it is needed. This approach is unique because it targets both patients’ behaviors and health professional practices to help close the gaps between what we know about arthritis management and the actual use of effective treatments. This innovative combination of health and digital media will help us modernize the way we deliver evidence-based treatment information for the 21st Century.
Injection-drug users are extremely susceptible to drug-related health risks, including HIV, hepatitis C and overdose. Although treatments for drug addiction are available, they are not always effective for those with the most severe cases of addiction. A key issue is many members of this vulnerable population remain outside the health care system, which exposes injection-drug users and those in their immediate communities to drug-related health risks. Previous research studies in Europe and Canada have shown that medically prescribed heroin can effectively attract and retain injection-drug users into the health care system and can ultimately improve the health of this vulnerable population. Unfortunately, the negative stigma attached to the medical use of heroin is a barrier to its implementation in many settings. However, an alternative strategy was suggested by a Canadian study, which demonstrated that a small group of participants receiving a licensed pain medication experienced similar health improvements as those receiving medically prescribed heroin.
Dr. Eugenia Oviedo-Joekes’ research is studying whether alternative drug addiction treatments can be used to reach vulnerable populations remaining outside the health care system. She is conducting an innovative clinical trial to test whether licensed pain medications can successfully treat the most severe cases of heroin dependency and is studying how this approach compares to medically prescribed heroin. After patients are effectively stabilized with injection treatment, she will determine if pain medication administered as an oral liquid can be used instead of injections.
Dr. Oviedo-Joekes is focusing her work on a subpopulation of women and Aboriginal people that have experienced high rates of victimization, including physical and sexual abuse, or violent or traumatic experiences, which dramatically impact their health. She hopes these treatments will directly benefit those with the most severe cases of heroin addiction and she will also measure the beneficial impacts in their communities.
Repetitive-use tendinopathy, formerly known as tendonitis, is a major cause of repetitive strain injury (RSI). The occupational costs of RSI are enormous: work-related injuries cost Canada $8.6 billion annually and an estimated one-third of workers' compensation costs in industry are due to RSI of soft tissues, particularly tendons. In 2001, 2.3 million Canadians reported an RSI, and the average time lost from work per case of tendon-related injuries was 79 days (Source: StatsCanada 2001). Despite the enormous clinical, societal, and economic significance of RSIs, there is only limited understanding of the mechanisms that cause them.
In order to establish new treatments for RSI, Dr. Alexander Scott has established an innovative tendinopathy research program. He is incorporating a multi-disciplinary approach from basic to clinical science, which integrates a number of different methods, including molecular and cell biology, biomechanics, and rehabilitation science. His work will focus on the role of new blood vessel formation as a feature of chronic tendon injury. This work promises basic insight into the biology of RSI as well as directly applicable knowledge to develop new therapeutic strategies. This will be the first research program in Canada to have a primary focus on the biology of work-related tendon overuse injuries using a multidisciplinary approach. The ultimate vision of this program is to find better treatments for work-related tendon injuries.
Youth and women working in Vancouver’s sex industry are among the most marginalized and vulnerable in Canadian society. The persistently high rates of health-related issues, violence, and mortality among sex workers, both in Canada and globally, highlights a desperate need for renewed public health interventions targeting the reduction of harms in this industry. Dr. Kate Shannon is working to investigate the different factors influencing the health and safety of youth and women working in the sex industry in Vancouver. Her team is studying the social (violence, work conditions) and structural (laws, regulations, urban renewal) contexts of sexually transmitted infection (STI) in this population. Specifically, her team is examining the different factors that influence the worker’s negotiating power during transactions and how this influences the risk of HIV/STI acquisition. Her research will involve the study and long-term follow-up of two groups of women: (1) 500 existing and new adult women working in both the street and indoor sex industry; and (2) 250 female youth aged 14 to 20 years who have exchanged sex for money, drugs, gifts, shelter, or other commodities in the previous 30 days. By evaluating and integrating different types of data, including individual mapping and neighborhood environment data (including violence and housing) from publicly available sources, she hopes to identify policies and harm-reducing interventions for this population. This study is among the first prospective studies of sex work in North America. Dr. Shannon’s team possesses a wealth of expertise in observational and intervention research, policy, and sex work. They are uniquely positioned to conduct this study, which aims to directly improve the health of some of the most marginalized youth and women in Canadian society.
Questions regarding the proper timing of various medical interventions arise frequently in health care. How often should people be screened for a type of cancer? How often should patients go for laboratory tests to measure the progress of an existing disease? What is the optimal time to initiate a therapy or to switch therapies when one appears to lose its effectiveness? These are difficult decisions because of the need to trade off costs and benefits under uncertainty. For example, screening too frequently results in high system costs as well as inconvenience (and possibly harm) to the patients being screened. On the other hand, treatment outcomes are almost always better when disease is treated earlier than later. Dr. Shechter’s research program aims to develop and apply advanced analytical techniques from the field of operations research (OR) to aid decision-making in questions of clinical timing. The methodological tools of OR were designed specifically to deal with complex decision-making under uncertainty and have been applied for more than 50 years in a variety of areas. With the growing complexity of medical decision-making and the increasing availability of patient medical data, these techniques have become extremely relevant for seeking cost-effective solutions to health-care problems. Clinical timing decisions alone provide a large class of difficult decisions that are well suited for study using these analytical techniques. Dr. Shechter’s research includes two specific projects that will analyze key timing decisions for patients with chronic kidney disease: 1) when is the optimal time to prepare an arteriovenous fistula for patients who eventually start dialysis?; and 2) how often should patients on the kidney transplant waitlist be screened for conditions that may put them at increased surgical risks should a donation become available? With a 500 per cent increase in chronic kidney disease among British Columbians over the past decade, improvements in treatment and screening policies can result in substantial health benefits to patients province-wide. Dr. Shechter will work closely with frontline decision-makers, including nephrologists and kidney transplant surgeons, to develop and validate useful data-driven decision models to address these questions.
According to the World Health Organization, obsessive-compulsive disorder (OCD) is one of the top 10 causes of disability. The disorder often begins in childhood and interferes with normal development. This disabling mental illness affects approximately 2 – 3 percent of British Columbians and, although treatable, is often under diagnosed.
The aim of Dr. S. Evelyn Stewart's research program is to improve the lives of BC children and families living with OCD. Her goal is to improve the evaluation and awareness of pediatric OCD in BC by conducting research to guide scientific and clinical understanding of OCD and its management by health professionals, and by establishing national and international linkages, which will lead to future research collaborations. Dr. Stewart's specific objectives for the first five years are to 1) create a unique research program within the new pediatric OCD clinic at BC Children's Hospital that is closely tied with the community, 2) establish a pediatric OCD DNA and research data site for BC, 3) launch a comprehensive patient-assessment method, and 4) investigate the outcomes and effectiveness of the program itself.
This program is unique, as it pulls together expertise from the clinic, the community and the laboratory. One important feature of Dr. Stewart's program is the effective transfer of new information between the clinic and the research lab in order to help the outcomes of practice inform research. Dr. Stewart anticipates this program will help limit the suffering and health-care costs related to OCD. The program is anticipated to develop into the first North American OCD Centre of Excellence.
Lungs are for life. Unfortunately, the most frequent long-term illnesses in children and babies are respiratory system conditions. Children's lungs can be damaged in many ways: bacterial and viral infections, asthma, or faulty genes causing thick mucus to accumulate in the lungs of children with cystic fibrosis. Even the oxygen and artificial ventilation needed to sustain the lives of premature babies can cause lasting lung damage. A feature shared by all these serious childhood lung diseases is that some of the damage is caused by activation of the innate immune system, which is an important part of our immune defense network. The innate immune system is like a “double-edged” sword. While innate immunity is essential for keeping us healthy, it can cause excessive lung-damaging inflammation if the activity is not carefully controlled.
To prevent lung damage, Dr. Stuart Turvey is examining the systems that control the activity of the innate immune system. These control elements are known as negative regulators. His team will study these negative regulators in a variety of childhood lung diseases spanning premature babies and lung infections through to asthma and cystic fibrosis. The unique aspect of this project, and of Dr. Turvey's group in general, is a commitment to translational research focused on people with lung disease. This means research results from the lab bench are applied directly to patient care.
Rather than relying exclusively on laboratory (animal or cell) models of disease, Dr. Turvey’s team plans to examine genetic material donated by people affected by infectious and inflammatory lung diseases. The results of this work will be an exciting starting point for gaining a better understanding of the causes of childhood lung diseases and developing new medicines to safely control the damaging inflammation that occurs in the lungs of so many babies and children.
Melanoma is the most dangerous type of skin cancer. The incidence and rate of death from melanoma is rising in Canada. Since 1988, the death rate from melanoma increased 41% in men and 23% in women, which is the highest rate of increase for any type of cancer. Melanoma is primarily caused by repeated sun damage, which leads to the accumulation of mutations in the genes that regulate the survival and growth of pigment cells in the skin. The disease has a molecular basis, so it only makes sense that a molecular approach is being taken to find new therapies to treat this deadly disease. Dr. Catherine Van Raamsdonk is taking a unique molecular approach to identify genes that may be involved in melanoma. By studying three mouse strains that have a darker dermis (the lower-most layer of the skin), Dr. Van Raamsdonk and her colleagues have discovered three genes named GNAQ, GNA11 and NF1 that are important for pigment cell growth and survival. By studying how these genes interact with each other and how they are regulated at different stages of development, she hopes to understand how they may contribute to melanoma. This work will help to reveal the molecular basis of melanoma as well as other cancers. For example, the NF1 gene is also mutated in human neurofibromatosis, a genetic disease in which patients develop disfiguring tumors and hyper-pigmentation of the skin. Dr. Van Raamsdonk and her colleagues have also discovered that GNAQ and GNA11 are mutated in 78% of human uveal melanomas, the most common type of eye cancer. This breakthrough is significant because the mutations associated with uveal melanoma were previously unknown. Dr. Van Raamsdonk is the only professor in the world examining the role of GNAQ and GNA11 in mouse pigment cells, making this work unique and essential. The information she gains may be used to prevent, diagnose, and treat different types of cancers, including melanomas.
