The brain or central nervous system (CNS) is especially vulnerable to permanent injury and loss of function following stroke, trauma and seizure or the onset of genetic disorders such as Huntington or Parkinson disease costing billions of dollars in health care every year and long-term loss of productivity. Despite major advances in understanding of neural development in recent years, a major challenge facing neuroscientists today is how to use this knowledge to help direct repair and rebuild the CNS after it becomes damaged. Dr. Jane Roskams uses the mouse olfactory system (nose) to study CNS repair because cells in the system have a remarkable ability to remodel, repair and regenerate, compared to other regions of the CNS. Olfactory system repair is driven by two types of cells — one that replaces lost neurons (specialized olfactory stem cells) and another that guides these replacement cells to their target (olfactory glial cells). As part of the only team in the world focused on these complementary research areas, Dr. Roskams has developed a series of tools and approaches to determine which specific cells are activated to replace damaged neurons, and to test the signals that drive this activity. She is also working to determine the unique ways that these cells contribute to repair following spinal cord injury and stroke. While transplanting either of these types of cells into injured or damaged CNS tissue could help with repair. Dr. Roskams’ work is focused on understanding how repair mechanisms work at the molecular level, with the goal of discovering if there are ways that injured cells might be manipulated into repairing themselves — a potential new way of addressing or preventing long-term CNS damage.
Archives: awards
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Improving youth sexual health in British Columbia
In spite of prevention programs that target risky sexual behaviours in youth, many BC teens continue to experience serious health and social problems related to sexually transmitted infections (STIs) and unplanned pregnancies. While untreated STIs can lead to pelvic inflammatory disease, infertility and increased risk of HIV, early maternal age can result in decreased future educational and employment opportunities for young mothers. As a Scholar, Dr. Jean Shoveller investigated the factors that play a role in the increased incidence of teen pregnancy and STIs among rural and remote BC communities. Now, Dr. Shoveller is working to reduce gaps in public health interventions related to youth sexual health by focusing on policy and program intervention research related to the health and social impacts of STIs and unwanted pregnancies amongst youth. Dr. Shoveller’s research will integrate participatory approaches to research (where youth are directly involved in the planning and implementation of research projects) with an analytical framework that examines how features of youth’s social contexts (e.g., gender, place, culture) affect youth’s sexual lives. Also, data that illustrate how context affects young people’s sexual health will be mapped to reveal how strengths and weaknesses in the health, education and social service systems affect youth’s sexual health. This research will provide researchers with new tools that can be used in new and unique participatory research opportunities that actively involve youth in research into this complex and sensitive topic and will provide public health policy makers and program planners with information to help inform decisions regarding improving and promoting youth sexual health.
Imaging studies: towards understanding the complications related to advanced monoaminergic disease and treatment
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.
The MaMS Study. Malignancy and Multiple Sclerosis: incidence and impact of beta-interferon treatment
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.
Apolipoproteins and Autoimmunity to Lipid Antigens
The immune system is designed to rid the body of infections and unwanted cells, such as tumor cells or virally infected cells. The decision to target a certain agent for elimination is made by recognizing that a component (antigen) of a bacteria or virally infected cell is «foreign» to the body. Sometimes, however, the immune system can mistakenly target «self» components in healthy tissue, which leads to autoimmune diseases such as multiple sclerosis (MS). White blood cells called T cells are the central players in this decision making and are classically known to target protein components. Recently, however, it has been found that lipid components (ie. fats) can also be targeted by T cells, which is a new paradigm in immune recognition. We have been studying how T cells recognize lipids, and found that a major blood protein, apolipoprotein E (apoE), which was previously known to carry lipids for metabolic purposes, is also playing a role in the immune system to promote the recognition of lipids. ApoE has been known to play a role in many diseases, including MS and atherosclerosis (the disease of blood vessels which leads to heart disease and strokes). These two diseases also share common features in that there is immune system involvement which causes harm, in MS directed against the fatty insulation of nerves (myelin), and in atherosclerosis, immunity against unknown agents, possibly lipids found circulating in the blood. Our findings integrating lipid metabolism by apoE and the immune system thus open up a new area of research of direct relevance to MS and atherosclerosis, and we will set out to demonstrate that lipids are targeted in these diseases, and how apoE is involved to promote this mistaken targeting. Understanding these mechanisms will allow us to better monitor these disease using blood samples from patients, and also point to new strategies to treat disease by dampening or altering the immune response to lipids.
Mechanisms of X-linked Dyskeratosis congenita
Dyskeratosis congenita (DC) is an inherited premature-aging syndrome that typically results in bone-marrow failure. Symptoms include abnormal skin pigmentation, abnormal or absent nails and white, pre-cancerous areas on the lips and in the eyes, mouth and other body openings. More than 80% of patients with DC develop bone-marrow failure, which leads to decreased production of all types of blood cells. Premature death is usually the result of bone marrow failure. Most cases of DC are caused by changes in the DKC1 gene on the X chromosome. DKC1 encodes a protein called dyskerin, which helps maintains chromosomes, in addition to its essential function of manufacturing protein synthesis machinery. A symptom-free mother carrying a DKC1 mutation has a 50% chance of transmitting it to a son who will develop the disease.
Using genetic and biochemical techniques, Dr. Judy Wong is working to determine the mechanisms of X-linked DC. There are more than thirty amino acid mutations of the dyskerin protein that are known to be associated with X-linked DC. Understanding the molecular events that give rise to X-linked DC will help predict how patients will be affected and assist in the development of genetic therapies. Dr. Wong plans to test the effectiveness of dyskerin gene replacement techniques in restoring normal activity in X-linked DC cells. Her work will also improve our understanding of how other physiological factors can compromise normal aging.
Spinal Cord Injury Proteomics
Each year, approximately 1,500 Canadians sustain an acute traumatic spinal cord injury (SCI). Disability from an SCI results both from the initial trauma, and secondary cell damage that occurs due to pathophysiological processes after the initial SCI event. Current research suggests that neuroprotective drugs need to be administered early after injury to head off secondary cell damage, yet current diagnostics aren’t able to determine and classify the exact severity of the spinal injury within this timeframe. This makes it difficult to predict how much spontaneous recovery can be expected and which treatment strategies will improve functional recovery. Using proteomics technologies, this team is working to identify and validate biomarkers to monitor the severity of spinal cord injuries (SCI), and allow the “real time” ongoing evaluation of candidate drugs in human clinical trials.
TB Research Group
Mycobacterium tuberculosis – the bacteria that causes tuberculosis (TB) – is the most devastating infectious agent of mortality worldwide: it is carried by one third of all humans and kills nearly two million people annually. In BC and throughout Canada, First Nations and Inuit communities are at an especially high risk, and more than 300 new or relapsed TB cases are reported each year. With the emergence of a strain that is virtually untreatable with current medicines, novel therapeutics are urgently required to target persistent bacilli and to contribute to more effective treatments of TB. This Team brings together individuals from different disciplines who are seeking to establish a foundation to develop strategies to control TB, focusing their studies on the bacterium’s inherent resistance to antibiotics, and its ability to persist in host cells.
Team for Monitoring and Control of Abnormal Brain Dynamics
The majority of treatments for neurological diseases involve drugs. Yet maintaining a steady state of medications in a person’s system may not be effective in targeting abnormal brain activity that is transient and oscillating. Therefore, patients may have to continually take drugs for conditions that only manifest themselves intermittently – such as with seizures – or to take drugs that disrupt normal brain activity. With a view to developing non-pharmacological interventions, this team is dedicated to measuring – and ultimately managing – disrupted brain function occurring at short temporal scales. Focusing initially on Parkinson’s Disease, the team is working to better pinpoint and understand subtle oscillations in abnormal brain activity, and developing and testing visual stimuli systems that have shown promise in disrupting these abnormal oscillations in the brain. The findings from this research will have broader impact with implications for many brain diseases.
Increasing consumer access to cognitive behaviour therapy (CBT) in British Columbia
The Provincial Health Services Authority and the BC Ministry of Health are jointly sponsoring a clinical practice initiative to improve the quality and availability of Cognitive Behaviour Therapy (CBT) for mental health and addictions in BC. While CBT has been established as an empirically supported treatment for many disorders, there has been a lack of availability of CBT in the community. Research is needed on issues related to dissemination and adoption/uptake of CBT. Another priority is evaluating the success of the joint CBT initiative by examining aspects such as changes in client care outcomes and cost-effectiveness. This award supports the creation of a team that will focus on developing a better, more integrated understanding of the most effective CBT dissemination methods. The team aims for its research effort to lead to increased access to CBT mental health services for British Columbians.