Each year, approximately 50,000 Canadians suffer a stroke—the number one cause of neurological disability leading to impaired balance and mobility. Almost 90 per cent of stroke survivors have difficulties with everyday tasks, a reduced tolerance for physical activity, a sedentary lifestyle and multiple secondary complications. Many of these complications can be reduced with rehabilitation.
As a MSFHR-funded scholar, Dr. Janice Eng researched the effectiveness of a specific exercise program in improving balance and mobility in people with stroke. Now, Dr. Eng is working to optimize the functional abilities of people with stroke through innovative and effective rehabilitation interventions. One of these treatments includes a novel, cost-effective therapy where the patient manages their own amount of therapy for the arm and hand using a self-guided program. Dr. Eng will conduct a series of clinical studies aimed at improving arm and leg function in people living with stroke. People with stroke will be invited to participate in these studies and measurements of their abilities will be evaluated before and after the treatment. Changes in their abilities will then be analyzed and compared to individuals with stroke who receive what is considered standard therapy.
The development of effective rehabilitation interventions will improve the functional abilities of people with stroke, enable participation in social roles and physical activities, reduce secondary complications, and enhance quality of life. Novel interventions can also serve as a model for rehabilitation interventions in populations with other chronic health conditions.
Attention-deficit/hyperactivity disorder (ADHD) is the most frequently encountered childhood onset disorder in primary care settings. ADHD is characterized by certain behaviours, most commonly: inattention, hyperactivity, and impulsiveness. Although preliminary research indicates that the biological roots of ADHD may involve certain areas of the brain, the link between the cognitive and behavioral manifestations of ADHD and its neural basis is poorly understood. Research shows that the midbrain’s dopamine system — a neural system associated with reward learning and reward-related behavior (reinforcement learning) — is abnormal in children with ADHD. To date, however, there has been little research regarding exactly how the disturbance of the dopamine system leads to this impaired reinforcement learning. Dr. Clay Holroyd is interested in the neurobiological mechanisms that underlie cognitive control — how people regulate their attention, thoughts, and actions in accord with high-level goals and intentions. Specifically, he is focusing on how people detect and correct their errors and, and how they learn from the consequences of their actions. Currently, ADHD research is an important component of his ongoing research program. Dr. Holroyd is investigating impaired cognitive control, error processing, and reinforcement learning in children with ADHD. Using behavioural experiments and computational modeling, he is researching whether the cognitive and behavioral impairments associated with ADHD are the result of the transmission of abnormal reinforcement learning (RL) signals from the midbrain dopamine (DA) system to the frontal areas of the brain involved in cognitive control. Developing a greater understanding of the link between the neural impairment in ADHD and learning and behavior is an important step towards creating a common and accepted model of ADHD; one that spans multiple levels of analysis, including biology, behavior and cognition. This research will provide a greater understanding of the neurobiological mechanisms that underlie cognitive and could lead to the development of new therapeutic treatments for children with ADHD.
Today’s cancer treatment is dictated by the anatomic location of the cancer, its histology, and how far it has spread. The Human Genome Project and the development of new drugs targeted against specific features of cancer cells have led to the possibility of individualized cancer care. This is a fundamental shift in cancer management and will involve integration of each patient’s inherited genetic characteristics and the molecular signature of their tumour. My laboratory uses genetic tools to predict inherited cancer susceptibility and genomic based tumour characteristics to determine therapeutic options. In British Columbia, the central referral system for cancer patients provides the opportunity to deliver equitable individualized cancer care across a whole population. I am fully committed to this challenge and dedicate my research, clinical practice, teaching, and administrative skills to this task. My clinical work occupies <25% of my time and involves the genetic based care of familial cancers. The remainder of my time is divided evenly between (1) research infrastructure development and furthering the translational research of my colleagues and collaborators and (2) the pursuit of my own research interests. My major research projects focus on the genetics and molecular pathology of hereditary cancers, with the goal of streamlining cancer susceptibility testing and identifying therapeutic opportunities for hereditary cancers and their sporadic counterparts. Current projects include the study of gastric, breast, and ovarian cancer susceptibility. My research in hereditary gastric cancer is already shaping the worldwide management of this cancer susceptibility syndrome. To develop useful laboratory tests based upon tumour characteristics, I developed and now co-direct the Genetic Pathology Evaluation Centre (GPEC) which is Canada's leading tissue based biomarker validation laboratory and a key element in the BC research landscape. My time spent directing GPEC and other such research entities is mutually beneficial as I am user of the research infrastructure I have helped to create. All of my projects are completely congruent with my stated vision of genetic based individualized cancer care for whole populations. Although this is an aggressive agenda, I believe my record in translational research during the first 4 years of my MSFHR scholarship indicates a great likelihood of future success.
Approximately 1,050 new spinal cord injuries occur every year in Canada, primarily in young people. There are currently approximately 40,000 Canadians living with a spinal cord injury (SCI). As a physician and neuroscientist, Dr. Brian Kwon is actively involved in discovering new ways to improve the prognosis of those with SCI. Experimental treatments that have shown tremendous benefits in animal models of spinal cord injury have not translated in human clinical trials. This discrepancy suggests important differences in the biological responses to spinal cord injury between humans and animals. Within minutes of a spinal cord injury occurring, the spinal cord swells at the injury site. This swelling reduces blood flow and oxygen to the spinal cord tissue and can subsequently result in further secondary damage. Dr. Kwon is researching whether draining some of the cerebrospinal fluid (CSF) that surrounds the spinal cord will reduce the pressure on the cord, restoring blood flow and minimizing the risk for secondary damage. In a clinical trial of patients enrolled at Vancouver General Hospital within 48 hours of their SCI, CSF samples will be taken and measured for proteins that regulate inflammation. This biochemical evaluation will offer the first human description of how these inflammatory proteins are expressed following injury, leading to new biomarkers or indicators of injury severity to assist with further research. The expression proteins will be compared with the expression of proteins in animal models to determine differences in response between humans and animals. Ultimately, these insights will assist researchers in developing therapies to improve the lives of patients with spinal cord injuries.
Intellectual disability (ID) is a diagnosis given to persons who have life-long cognitive and adaptive impairments that commence in early life. ID affects about 1-3% of the population, thus nearly 1 million Canadians have an ID. The cause of ID is unknown in at least 40% of all cases. Recent reports have suggested that very tiny chromosome changes are the cause of many cases of ID. These tiny chromosome anomalies are usually not seen using routine microscopic analysis. However, recently developed microarray technology provides an opportunity to detect these very small changes.
Dr. Evica Rajcan-Separovic has used this technology to look for such abnormalities in 200 subjects with ID and have detected very small genetic changes in 16% cases. Some of the genetic abnormalities were seen in more than one individual. Her team plans to extend their array study to 400 more ID individuals in the next 6 years and to examine using molecular methods another 2000 subjects with ID to see if they can find additional individuals with the same abnormalities. By studying a larger number of individuals with the same chromosome change, they will be able to determine what physical features and medical issues are due to that genetic change.
Rajcan-Separovic's next step will be to develop Health Care Watches for each new condition identified. These will describe expected health issues, so that families and physicians can be better prepared to care for individuals with these new genetic syndromes. This approach will eliminate costly multiple testing and searching for answers, and should allow optimal care and health for persons with ID.
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, estimated to affect 100,000 Canadians and is characterized by deficiency of the neurotransmitter dopamine (DA) as a consequence of dopaminergic neuronal death. Existing treatments ameliorate the symptoms, but they do not seem to alter disease progression. Furthermore, treatment often induces undesired side-effects such as motor complications and high risk taking behavior such as compulsive gambling. Positron emission tomography (PET) is a non-invasive imaging modality that uses radioactive tracers to obtain information about biological function in-vivo; depending on their chemical form, radiotracers tag different biochemical processes. PET is thus ideally suited to investigate the complex neurochemical changes associated with neurodegeneration. Using PET we have already provided significant insights into the motor aspects of disease-induced complications; an alteration in the pattern of the neuronal release of DA has been identified as being involved in the occurrence of motor complication. The main goal of this research program is to further develop and use novel imaging techniques to gain insights into the impact of different treatment strategies on motor complications and into treatment-induced psychiatric complications. Studies on human volunteers will be performed on a new, state-of-the art human PET brain scanner. This scanner, existing only in 15 PET centers worldwide, while providing and unprecedented amount of information, requires development of accurate data manipulation and interpretation algorithms, which are another part of this research program. A very important aspect in medical research is the ability to develop and investigate animal models of disease to be able to investigate disease in further detail in a more controlled environment. A third important part of this research program will be the in-vivo investigation of rodent models of PD and their relation to other diseases such as, for example, Alzheimer’s, since there is evidence of some clinical and pathological overlap between neurodegenerative diseases. A unique strength of this program is its ability to bridge advancement of knowledge with the advancement of methodological approaches. This aspect will contribute towards the establishment of a more comprehensive imaging environment aimed at the investigation of neurodegenerative and related disease, which is the program long term goal.
Multiple sclerosis (MS) is thought to be a chronic autoimmune disease of the central nervous system, which attacks myelin, a protective material that insulates nerve fibers in the brain and spinal cord. Over time, MS can cause loss of balance, impaired speech, extreme fatigue and problems with vision. Currently there is no cure, but treatment with beta-interferons (IFNBs) is available to reduce the frequency of MS attacks. Recent research suggests that the use of IFNBs may increase the risk of cancer. Given the estimated 75,000 Canadians with MS and the increasing popularity of the MS drugs, even a moderate increase in cancer risk could translate into a substantial number of new cancer cases.
Dr. Helen Tremlett is conducting the first study in North America to investigate the effect of IFNB on cancer risk in an MS population. Dr. Tremlett will examine more than two decades of BC data created by linking the BC Multiple Sclerosis Research Groups’ database with the BC Cancer Agency's Registry to determine the overall risk of cancer in the MS population, and the risk among MS patients treated with beta-interferon compared to the general population. Dr. Tremlett’s research will help to determine the background risk of cancer among MS patients, whether widely used treatments are associated with increased risk of cancer, and will also facilitate researchers in evaluating future drugs licensed for MS.
Brain injuries can have lasting detrimental effects on the way someone thinks and behaves. Prosopagnosia, a rare disorder that can result from brain injury, impairs the ability to recognize faces. Patients with this condition may have trouble recognizing family members, coworkers, and even their own face in the mirror. This disorder is debilitating because everyday interactions rely on being able to recognize people. For example, people usually act quite differently when speaking to their boss or their spouse. With her MSFHR award, Kirsten Dalrymple is studying how the healthy brain recognizes faces and how this function is impaired with prosopagnosia (sometimes known as face blindness). Certain brain activations occur when someone looks at a face. Dalrymple will record and compare how brain activations differ between people who have prosopagnosia and those who function normally. In addition, most people remember things better when there’s a connection to themselves, rather than a reference to something unfamiliar, like the face of a stranger. Dalrymple is investigating whether or not this “self-reference” ability is present in people with prosopagnosia, who may be unaware that they are looking at their own face in a picture, rather than the face of a stranger. Her findings could be used to help patients rehabilitate from, or compensate for, the effects of this disorder.
Sexual dysfunctions play a significant role in depression, anxiety, stress, and marital/relationship satisfaction. Female Sexual Arousal Disorder (FSAD) affects approximately 1/4 of women aged 18-59. However, there are no established treatments for this disorder, with drug therapy trials yielding inconclusive and contradictory results. Recently, researchers and clinicians have disputed the current classification of FSAD as it only involves impairments in physiological sexual arousal and ignores the subjective aspect that the majority of women report. As a result, experts in the field have proposed a new classification involving three specific FSAD subtypes. Building on her research as a MSFHR-funded Master’s student, Carolin Klein is conducting a series of three experiments using alternative modes of activating the sympathetic nervous system to extend and replicate previous findings on these subtypes of FSAD. Carolin aims to better understand sexual functioning and the relationship between physiological and subjective sexual arousal in women in order to improve treatments. If further research continues to support the delineation of FSAD into separate subtypes , it may explain why treatments that increase physiological arousal appear to have no, or only a minimal effect on subjective arousal, and vice versa. Accordingly, separate treatments will be needed depending on the FSAD subtype.
Fractures of the main bone in the lower leg, known as the tibia, cause local bleeding, and tissue swelling within the compartments of the leg. In some patients, pressure within the compartments rises sufficiently high to prevent blood flow and cuts of the oxygen supply to intracompartmental muscles, nerves and other tissues. This condition is known as acute compartment syndrome. It is a surgical emergency and requires immediate identification and surgical treatment to save the function and viability of the lower leg. Delay in diagnosing this condition exposes the patient to increased risk of local muscle loss and a wide range of severe complications which requires multiple surgical procedures, prolonged hospitalization and even amputation of the affected limb. At the present time, diagnosis of acute compartment syndrome is mainly based on the clinical observation which is not always reliable and early. Measurement of intra-compartmental pressure can help to confirm the diagnosis but requires an invasive procedure which has some drawbacks. It is believed that direct monitoring of muscle oxygenation may provide early and precise diagnosis of this condition. Near infrared spectroscopy (NIRS) is a noninvasive and continuous method for monitoring tissue oxygenation. Babak Shadgan, a sport medicine researcher, is studying whether careful monitoring of lower leg muscle oxygenation in fractured leg patients who are in a higher risk of acute compartment syndrome may allow for an early diagnosis of this critical condition. If effective, this new method would improve speed and accuracy of diagnosis, leading to improved care for patients and substantial health care cost-savings.
