The number of individuals suffering from chronic obstructive pulmonary disease, or COPD is on the rise in Canada and around the world. COPD, is an inflammatory disease primarily associated with lung inflammation. Inflammation also extends beyond the lungs, and the presence of inflammatory factors in the blood causes blood vessel and heart disease, increasing a COPD patient’s risk of heart attack and stroke. Exercise training is known to have anti-inflammatory effects that are beneficial in the treatment and prevention of a number of chronic conditions. However, the effects of exercise on inflammation in the airways and blood of COPD patients is not well understood. It is also unknown whether exercise training can reverse some of the detrimental effects of inflammation in the blood vessels and brains of patients with COPD and reduce their risk of having a heart attack or stroke. To answer these important questions, Dr. Neil Eves will be conducting two studies. His first study will investigate how exercise training affects the airway and blood inflammation of patients with COPD. His second study will investigate how exercise training improves blood vessel function in patients with COPD and whether these improvements are related to changes in inflammation. Reducing inflammation with exercise in patients with COPD could greatly improve the health of these patients and reduce secondary morbidities associated with the disease.
Year: 2011
Endothelial cell regulation of T cell responses
Organ transplantation is a life-saving procedure for many individuals. Unfortunately, the long-term success of this procedure is compromised by the rejection of the transplanted organ(s) by the recipient's immune system. T cells are specialized cells of the immune system that protect against infections but that recognize and damage transplanted organs. Understanding how T cell responses are controlled will help to develop new methods to increase the long-term and specific acceptance of transplanted organs.
Dr. Jonathan Choy's research is focused on understanding how T cell survival and persistence is regulated and how these processes contribute to organ transplant rejection. By understanding this, Dr. Choy intends to find new ways of controlling the immune response against transplanted organs. Preventing rejection will improve outcomes for the approximately 2,000 Canadians who receive solid organ transplants each year, as well as for the many Canadians who are already living with transplants.
The role of emotion regulation in borderline personality disorder and self-injury
Borderline personality disorder (BPD) is among the most complex, misunderstood, and stigmatized mental health problems. It is a serious psychiatric condition characterized by instability in relationships, emotions, identity, and behaviour that often induces intense emotional suffering and places affected individuals at high risk of suicide and self-injury. Approximately 10% of individuals affected by BPD die by suicide, 75% have attempted suicide, and 70-80% self-injure. BPD is also a significant concern for the public health-care system. Patients affected by BPD represent up to 20% of psychiatric inpatients and heavily utilize outpatient and hospital emergency services. In fact, the estimated costs to the health-care system per year for each BPD patient range from US$12,000–$30,000. Self-injury and other problems in BPD appear to be related to problems in the management of emotions, or emotion regulation problems.
Dr. Alexander Chapman’s research aims to better understand and treat BPD and related problems, such as self-injury and suicidal behaviour, by examining the role of emotions in BPD and self-injury. Research in his lab, the Personality and Emotion Research Laboratory, includes a variety of studies aimed at better understanding what causes and maintains BPD and self-injury, as well as studies designed to help us understand how to effectively treat BPD. He is also conducting studies on the risks and protective factors for self-injury.
Dr. Chapman’s short-term goal is to continue to develop his research on BPD in two key areas: (1) the role of emotion regulation in BPD and self-injury, and (2) effective treatments for BPD and NSSI. He has several grants for studies in these areas and hopes to expand this research over the next five years. In the long-term, Dr. Chapman would like to develop an interdisciplinary research, treatment, and education centre focused on BPD, self-injury, and related health problems. Such a centre would be unique in Canada and would have the potential to significantly improve our understanding and treatment of BPD as well as the education and training of junior researchers and professionals.
Optimal Timing of Medical Decisions
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.
Physical activity in individuals with chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a lung condition that affects more than 75,000 British Columbians. People with COPD have a shortness of breath, chronic cough, and can experience difficulties with the activities of daily life, such as showering, walking, and social activities. Many people with COPD have regular flare-ups, or exacerbations, of their lung condition. These exacerbations result in a severe shortness of breath and overall weakness and fatigue and sometimes lead to long hospital stays. These flare-ups and long hospital stays can cause severe problems with activity tolerance, which then further increases the risk of future flare-ups.
The objective of Dr. Pat Camp's research program is to investigate how physical activity can improve the health outcomes of people who are hospitalized with a COPD flare-up. This research program will include a systematic literature review to summarize the current state of knowledge, validating tools to measure activity in hospitalized COPD patients, and determining if exercise programs for hospitalized patients can improve their quality of life and health outcomes. In addition, Dr. Camp's research program will include projects that incorporate patient input about what activities are important to them, which will indicate the level and type of activity that is necessary in order for these patients to be discharged safely from the hospital.
By developing a thorough understanding of how exercise leads to increased health in COPD patients, this research program aims to improve the quality of life and overall health of patients hospitalized with acute COPD flare-ups. Future work will extend these innovations to other chronic lung disease populations, such as patients with lung transplants or interstitial lung disease.
Drug impaired driving: Evaluating the threat to traffic safety
Motor vehicle crashes cause 15,000 serious injuries and over 2,000 deaths in Canada annually. The contribution of drug-impaired driving to these tragedies is unknown, but suspected to be significant. This lack of knowledge hinders the development of effective traffic safety policies to prevent drug-impaired driving.
The research of Dr. Jeffrey Brubacher aims to prevent injuries and fatalities resulting from motor vehicle crashes. His research program consists of three inter-related themes:
- Cannabis and motor vehicle crashes. This five- year study will examine 3,000 injured drivers from five BC trauma centres to determine whether there was recent marijuana use before their crashes and whether or not the driver caused the crash. The study will provide important information about the role played by marijuana in causing car crashes.
- Prescription medications and motor vehicle crashes. This project will involve combining BC prescription data with BC driver records, including traffic accident reports, to determine whether or not drivers are more likely to be involved in a crash when they are taking prescription medications such as sleeping pills or pain medications.
- The Injured Driver Platform. This study will provide information on the motor vehicle crash risk associated with recreational drug use. Over an initial three-year period, medical data will be collected and interviews will be conducted with injured drivers at five BC trauma centres, and drivers will then be followed for two years after their original crash to determine how often they are responsible in other accidents or drive while impaired.
This project will help to identify risk factors for impaired driving which may be used to develop targeted interventions to prevent this risky behaviour. Dr. Brubacher's research will contribute to an international effort to understand the role played by prescription medications, marijuana, and other illegal drugs in causing motor vehicle accidents. He will present his findings to government officials so they are better able to develop effective road safety policy and public education campaigns targeting impaired drivers and, by doing so, to improve safety on our roads.
Understanding the mechanisms of experience and injury based cortical plasticity
Strokes are caused by the interruption of blood flow or the rupture of blood vessels to the brain. This sudden loss of brain function can damage the brain centers that sense or move parts our body, profoundly impacting both physical and mental functions. As a result, stroke is the number one cause of acquired disability in adults around the world. Some stroke survivors are able to recover more quickly and more completely than others. Although recovery is influenced by the location of damage in the brain and the extent of the damage, recovery is also influenced by the brain's innate ability to initiate repair and re-wire damaged blood vessels and neuronal circuits in surviving regions. At the present time, we do not yet know why this re-wiring takes place in some patients but not others, nor do we know how to manipulate this process. What we do know is that this repair process can vary between patients and that some patients, such as diabetics, have a poorer prognosis following stroke.
Dr. Craig Brown's lab will use advanced imaging technologies to assess brain structure and function to understand how the brain is able to repair itself following a stroke and to understand why this is such a variable process between different patients. His research program is focused on three distinct yet complimentary lines of research, including: 1) understanding the impact of diabetes on recovery from stroke; 2) using electrical nerve stimulation to improve stroke recovery; and 3) elucidating the cellular/molecular mechanisms of learning or experience-based brain "plasticity".
As a result of this innovative research, Dr. Brown hopes to better understand the brain's plasticity associated with normal (learning/memory) and pathological (diabetes/stroke) brain states. His intent is that this work will stimulate new therapies for improving brain function both in normal situations and after stroke, particularly in patients who have previously had a poor prognosis.
New synthetic methods and strategies: Enabling natural product drug discovery
Natural products are chemicals produced by living organisms that encompass a fascinating range of structural diversity and potentially useful pharmaceutical activities. Some of the better-known natural products include anti-bacterial compounds derived from fungi (e.g., penicillin), analgesics such as salicylic acid, derived from the bark of willow trees, and paclitaxel, an anti-cancer compound isolated from the Pacific Yew tree. In fact, over half of the drugs approved by the FDA in the past 25 years are derived from or inspired by natural products, and the near-doubling of the average Canadian’s life expectancy in the 20th century is largely attributed to medical advances based on these compounds.
Recent advances in biochemistry and molecular biology have guided the discovery of many new natural products. However, the limited quantities of natural source materials and environmental concerns associated with harvesting the producing organism highlight the importance of using alternate methods to synthesize these biologically active compounds in the laboratory. Thus, through a total synthesis approach, organic chemists are able to provide a renewable source of the natural product and generate sufficient quantities for extensive biological testing.
The focus of Dr. Robert Britton's Natural Product Research Program is the total synthesis of natural products that represent potential lead candidates for the treatment of human diseases. In particular, his group is focusing on developing novel synthetic pathways to manufacture sufficient quantities of eleutherobin and biselide A, two natural products that hold potential for the treatment of cancer, as well as a family of imminosugars that represent leads for the treatment of diabetes, viral diseases, and lyposomal storage disorders. The work of his team involves the development of innovative synthetic reactions that will allow them to construct complex natural products in a straightforward manner from simple chemical building blocks. The synthesis of these molecules will also enable the discovery of new substances that are similar in structure to these natural products but with potentially improved pharmaceutical properties.
Innate immunity and its influence on cardiovascular function
In Canada, severe infection, or sepsis, is the most common acute illness causing death. Patients with severe infections can go into shock as a result of progressive cardiac collapse and can die within 24 to 48 hours. The mortality rate of sepsis is 40%. The fact that this rate has not changed in the last 30 years illustrates that very little is known about how infection causes cardiovascular dysfunction and that very little is known about the best ways to prevent this from occurring.
Dr. John Boyd's research program is using a two-pronged approach to understand how sepsis causes progressive cardiac collapse. The objective of his clinical research program is to identify prognostic factors and to characterize the cardiac response to infection in patients with sepsis. Specifically, he is focusing on very early enrollment of acutely ill patients with infection presenting to the St. Paul's Hospital emergency department in order to identify prognostic factors such as new biomarkers and the presence of emerging infections. He will characterize their cardiovascular response to infection using a bedside cardiac ultrasound. Although previous work in this area has been done, patients were recruited from critical care units 24 to 36 hours following admission, too late to identify prognostic markers and intervene to improve outcome.
As a complementary approach, Dr. Boyd's pre-clinical (basic) research program is taking a molecular approach and using the immune system as a tool in the fight against cardiovascular collapse. He has identified a "counter-regulatory" receptor which appears able to reverse the heart damage induced by other receptors in the same family. The identification of this receptor will hopefully lead to the development of a targeted intervention for sepsis-related cardiovascular dysfunction. Dr. Boyd's clinical research program aims to answer simple but as-yet unstudied questions such as the optimal volume of IV fluid and how one can reliably diagnose infection. Although the results of his laboratory work are not yet close to reaching the bedside, they may potentially lead to therapies in the future.
A program of research to optimize public health immunization programs
Vaccines and immunization programs are the best way to prevent infectious diseases, improve child health, and save lives. According to the Public Health Agency of Canada, vaccines have saved the lives of more babies and children than any other medical intervention in the past 50 years. Through immunization, we have eliminated smallpox and have nearly eliminated eight other deadly diseases of childhood, including chickenpox and some kinds of pneumonia and meningitis. We need to continue to immunize all children so that we maintain high levels of protection throughout communities, which will prevent these diseases from re-emerging. Despite having province-wide immunization programs in place, not everyone gets vaccinated, as shown by several disease outbreaks in the past few years.
Dr. Julie Bettinger is working to address key questions about vaccines and immunization programs to ensure optimal disease protection in the population. Her research assesses the effectiveness of existing vaccination programs, evaluates the effectiveness of new vaccines, and also studies the best way to deliver them to children, adults and communities. Her approach uses quantitative and qualitative methods and includes collecting and analyzing surveillance data on select vaccine-preventable diseases and vaccine-adverse events from the Canadian Immunization Monitoring Program Active, an active surveillance network in 12 pediatric centers across Canada.
Dr. Bettinger’s research also focuses on evaluating the safety and effectiveness of vaccines through grant-funded clinical trials and observational studies and promoting improved immunization uptake through qualitative studies that assess the factors affecting vaccine use. Her work is used by local, provincial, and national public health decision makers, other research scientists, health care providers, and the public. This work, which is conducted at the Vaccine Evaluation Center at the Child and Family Research Institute and BC Children's Hospital, will create a centre for applied, population-based immunization research unique to BC and Canada.