A major goal of neuroscience research is to understand the neural changes that underlie adaptations of the motor system and to use this understanding to promote healing after injury. David McVea is studying the role of sensory input in this process from two different perspectives. First, he is testing the idea that muscle spindles, which respond to changes in muscle length, help determine when changes in the motor system are needed and subsequently spur changes in neural circuits. Second, he is studying how spontaneous muscle twitches in very young animals provide sensory feedback that helps to calibrate and organize the brain’s motor circuits. Mr. McVea is using unique optical recording and stimulating techniques to address these topics. Voltage- and calcium-sensitive dyes allow for simultaneous recording of neurons that are active across large regions of the brain. At the same time, lasers can be used to activate any part of the surface of the brain in mice that express the light-sensitive ion channel Channelrhodopsin-2. Because dyes and laser light are applied to the intact surface of the brain, all neural networks and connections are intact, meaning findings are representative of natural functions. This research will provide valuable information about the fundamental ways in which the human brain develops and recovers after injury. Furthermore, the results could inform the development of new treatments that increase or even artificially enhance sensory feedback to maximize the recovery of people who have suffered brain injury.
Research Location: University of British Columbia - Vancouver Campus
Light-based mapping of cortical reorganization after stroke in channelrhodopsin-2 mice
Stroke is the leading cause of adult disability. Although the physical damage is irreversible, many deficits seen immediately after a stroke disappear in the following weeks. This spontaneous recovery is partly due a to reorganization of the brain’s circuitry. The adult brain was long thought to be hardwired, but new evidence has demonstrated that the firing patterns of neurons and the connections between them are constantly changing, giving the brain the flexibility to learn, form new memories and adapt to injuries. This plasticity is especially evident after a stroke. Surviving brain areas are not only able to compensate for the absence of neurons lost to stroke, but can even take on functions formerly carried out by the destroyed area. However, whether rewired neurons in reorganized brain regions maintain the ability to perform their original duties has yet to be determined. Enhancement or modification of the brain’s natural repair processes represents a logical target for new stroke treatments, of which there are few. Thomas Harrison’s research will characterise brain plasticity during the period of spontaneous recovery after stroke using a variety of methods, including a new light-based mapping technique. He will track reorganization from the level of brain regions down to single neurons in transgenic mice before and after stroke. The resulting improved understanding of stroke-induced plasticity may enable the identification of the natural mechanisms of recovery that are most beneficial, and provide the opportunity to screen drugs or therapies for their ability to facilitate these biological pathways. In a larger sense, Mr. Harrison’s research will also advance our understanding of plasticity in the adult brain, which has important implications for learning, addiction and recovery from other forms of brain damage.
Probing the gastrointestinal microbiota for microbial determinants of asthma
Allergic asthma affects over 100 million people worldwide and more than 20 percent of Canadians. Furthermore, it is increasingly prevalent among people living in industrialized countries. While the underlying cause(s) of asthma remain unknown, there is increasing evidence to suggest that the intestinal microbiota (normal flora) plays an important role in the development of atopic diseases. Data from several large birth cohort studies have indicated that there may be a strong association between alterations in the intestinal microbiota as a result of antibiotic use and increases in the incidence of allergy and asthma in young children. However, the role of the intestinal microbiota in asthma has not yet been explored experimentally, and no attempts have been made to identify microbial species that may be associated with or hinder the development of asthma. Consequently, Shannon Russell is researching how changes in the composition of the intestinal microbiota may induce changes in asthma susceptibility. She is doing a series of experiments designed to determine whether antibiotic treatment during the early stages of life may alter or delay normal immune development and predispose a person to allergic-type diseases like asthma. This research could establish entirely new roles for the intestinal microbiota and may ultimately aid in the development of novel therapies (e.g. probiotics, prebiotics, narrow spectrum antibiotics), to treat or prevent allergic diseases including asthma.
Job accommodations: Perspectives from people with bipolar disorder
Bipolar Affective Disorder (BD), also known as ‘manic depression,’ is a chronic, often recurrent condition that affects more than half a million Canadians. It is characterized by changes in mood and behaviour, which range from elevated, euphoric and irritable (mania), to sad, withdrawn and hopeless (depression). While symptoms such as depression and euphoria can be controlled to some degree by medications, they can still result in significant challenges for individuals living with the disorder. Several studies have shown an association between BD and impairment in social roles such as work. Notably, people with BD rate work as the role most important to their quality of life, and the ability to maintain financial independence and contribute to the social fabric of our world is tied to how people work. Consequently, satisfactory employment is associated with improved health outcomes. However, the ability of people with BD to engage in work varies widely. Symptom recovery from an episode of BD occurs before functional and occupational recovery, which suggests factors beyond clinical symptoms can influence a person’s capacity for employment. In her research, Sandra Hale is exploring both formal and informal job accommodations with a view to improving employment outcomes for people with BD. Formal accommodations are defined as changes made to job structure and/or demands, documented by employers, disability management or vocational rehabilitation services. Informal accommodations are defined by the person with BD to address workplace issues or job demands. The results of Ms. Hale’s project will be shared with health care providers and mental health organizations and may help inform policy promoting access to information about job accommodation for people with BD.
Understanding the influence of early childhood sexual trauma and resiliency on health outcomes among young Aboriginal people who use drugs in British Columbia
Recent research has determined that young Aboriginal people who have been sexually abused and who use drugs are at greater risk of several negative health outcomes including Human Immunodeficiency Virus (HIV), infection. It is now well recognized that building resiliency is fundamental to the success of traditional Aboriginal health care practices and that cultural buffers may moderate vulnerability. There are a number of aspects to building resilience including attending to the mind, the body, the emotions and the spirit and, notably, there may be gender and age-related differences in resilience dynamics. Consequently, focused research is required to develop practical theories of resiliency and targeted interventions that will address trauma and facilitate stress coping among Aboriginal young people. To that end, Margo Pearce is investigating specific questions about the role that historical trauma and protective factors have with respect to vulnerability to HIV and hepatitis C (HCV) among young Aboriginal people in BC. She is utilizing existing data from the Cedar Project, an ongoing initiative funded by the Canadian Institutes of Health Research that monitors HIV and HCV risk among 600-1000 young indigenous people aged 14-30 who use injection and non-injection drugs. She is analyzing gender differences in health outcomes over time related to early childhood trauma amongst the Project participants. Ms. Pearce’s work will provide a better understanding of the protective factors that prevent specific adverse health outcomes among young Aboriginal men and women. Furthermore, it will address trauma and protective factors from a global public health policy perspective.
Exercise Intensity Prescription in Breast Cancer Patients Undergoing Chemotherapy Treatment
Most people today know someone affected by breast cancer. The statistics are startling, one in nine women is expected to develop breast cancer during her lifetime, but thanks to modern therapies, including chemotherapy, only one in 28 is expected to die from it, and many women go on to have a normal life expectancy. Chemotherapy , while effective, is associated with many negative short-term side effects. Importantly, exercise programs during chemotherapy provide a beneficial influence on many of the treatment-related side effects, but the specific parameters of exercise associated with optimal benefits remain unclear. Furthermore, studies of chemotherapy and exercise use a method of exercise intensity prescription that does not account for chemotherapy side effects: often, the prescription will be based on the body's response to exercise prior to chemotherapy treatment. Amy Kirkham is undertaking research to provide information on how the body changes with respect to exercise ability throughout chemotherapy treatment – information that is not currently available. Specifically, she will frequently test indicators of physical fitness in a group of breast cancer patients who are participating in an exercise and chemotherapy study, to analyze and compare the changes between tests and over time. Additionally, she will try to develop and validate a simple exercise test that can be used easily and often to adjust the exercise intensity prescription of breast cancer patients currently involved in a chemotherapy and exercise study. The results of Ms. Kirkham’s research could lead to the development of a more accurate method for prescribing exercise for cancer patients, and ultimately affect how other research on cancer and exercise is conducted in the future.
The effect of hyperoxia on baroreflex function in patients with sleep apnea
Obstructive sleep apnea (OSA), is a condition characterized by several stops and starts in breathing during sleep. This is caused by the collapse and re-opening of throat muscles. Unfortunately, the estimated one in four men and one in ten women who suffer from this condition are four times more likely to suffer from a stroke. The reasons for this phenomenon are not clear; however one likely explanation is an impaired ability among people with OSA to maintain normal blood pressure. In healthy individuals, when blood pressure increases the body reacts with a series of processes in order to bring blood pressure back down to normal levels. These processes are collectively called the baroreflex. However, the baroreflex is impaired in people with OSA, which results in dangerously high blood pressure and consequently, an increased risk for stroke. To-date, research has shown that baroreflex function is not only a powerful predictor of stroke, but also has strong prognostic value following a stroke. Indirect suggestions have been made of a potential improvement of the baroreflex in healthy humans when breathing supplemental oxygen (i.e. breathing high levels of oxygen). However, this remains to be investigated in people with OSA. In what is the first study to evaluate the effectiveness of supplemental oxygen in improving the baroreflex function in OSA, Jordan Querido is evaluating cardoirespiratory variables, including ventilated oxygen and carbon dioxide levels, sympathetic outflow, blood pressure, stroke volume, and heart rate, in both OSA patients and a group of healthy controls. Additionally, he will investigate the mechanisms which place OSA patients at greater risk for stroke, thereby potentially reducing their risk of stroke, and improving the prognosis following stroke.
The Role of Gap Junction Proteins in cytoskeletal rearrangements in B-lymphocytes
B-cell lymphomas are the most common type of blood cancer, accounting for 80-90 percent of non-Hodgkin’s lymphomas. Because lymphoma cancer cells can so readily spread from the blood stream to other tissues in the body, it is also a highly fatal form of disease. The key to preventing the spread of B-lymphomas is to prevent the proliferation and migration of these cancerous cells. To that end, an understanding of the underlying cellular processes is essential to the development of effective therapies. Recently, the Gap junction protein connexin43 (Cx43), was shown to cause neuronal migration in the brain. This novel role for gap junctions has led to speculation that Cx43 may be important for the migration of other cell types. Further, Cx43 expression on B-cells is important for hematopoiesis in the bone marrow, however the function of Cx43 on mature, circulating B-cells has remained elusive. Letitia Falk’s research involves a systematic dissection of the role of different protein domains of Cx43. Additionally, she is investigating the migration of B-lymphoid tumour cells expressing wild type and mutated forms of Cx43 in mouse models of tumour metastasis. These experiments will provide insight into processes that underlie normal lymphocyte development as well as the regulatory processes involved in the metastasis of B-cell leukemias, lymphomas and myelomas. Understanding in this area has the potential to aid in the development of novel anti-cancer therapeutics for the treatment of lymphoma cancers.
Visual-spatial attention and falls risk in seniors: Do fallers show impairments in reflexive orienting?
Seniors who fall and sustain injuries or worse, injury-related deaths, represent a major health concern. Approximately one-third of seniors over the age of 65 experience one or more falls per year, 20 percent of which require medical attention. In Canada, falls result in over $2.4 billion annually in direct health care costs. A growing body of research suggests that cognitive factors, such as visual-spatial attention, play a major role in a person's risk for falling.
In an earlier study, Lindsay Nagamatsu found that seniors who are prone to falling (fallers), may be less likely or slower to notice hazards while navigating within their environment. In other words, fallers appear to have a narrowed focus of attention compared to non-fallers. This may cause them to overlook hazards or obstacles and prevent them from safely navigating the immediate environment, and avoid falling. Failing to notice a step or a curb, for example, may lead to a fall.
In this, her second, follow-up study, Ms. Nagamatsu will determine whether other aspects of attention are also related to falls. Her research focuses on examining automatic attention in senior fallers through a series of carefully designed experiments. Identifying the causes of falls in seniors is important because success will guide strategic interventions to prevent falls and consequently reduce individuals' injuries and societal health care costs. The results of this study could also be applied to develop novel risk screening strategies for fallers.
Structural analysis of proteins involved in bacterial cell wall biosynthesis
Antibiotics play an essential role in the treatment of bacterial infections. However, the overuse of antibiotics has resulted in the emergence of numerous drug resistant strains of important human pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE). These, and related bacteria, represent major threats to human health if tools cannot be developed to combat these so called “”superbugs””. Potential targets for the development of these new antibacterial treatments include the enzymes involved in the production of the bacterial cell wall. Robert Gruninger’s research is focused on characterizing distinct aspects of cell-wall biogenesis. By clarifying the three dimensional structure of these enzymes, it will be possible to design drugs that will block their function, and combat the development and spread of “superbugs”.