Toxoplasmosis is a serious human pathogen carried by about one-third of the population. People develop toxoplasmosis either after ingesting undercooked meat that contains T. gondii cysts, or by coming into contact with cat feces from an infected animal. Once infected, healthy adults initially show a range of temporary flu-like symptoms; however, while these symptoms pass, the parasite Toxoplasma gondii remains in the body for life, with limited drug treatment available. Infection during pregnancy can cause miscarriage, neonatal death and a variety of fetal abnormalities, including developmental delays. It is also harmful to those whose immune systems are compromised, such as those with HIV/AIDS, cancer or who have had an organ transplant. Very little is known about how T. gondii causes disease. Dr. Martin Boulanger is studying the structure of host-pathogen interactions to determine the activities that allow T. gondii to attach to and invade human cells. With this information, treatments can be developed to prevent or manage Toxoplasmosis. This work will also apply to better understanding of other parasite-caused disease such as malaria and cryptosporidiosis.
Research Location: University of Victoria
Exploring and exploiting the protein psoriasin as a new target for breast cancer therapies
Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer, and the protein psoriasin is one of the most highly expressed genes in DCIS. Psoriasin is present at abnormally high levels in many pre-invasive breast cancer cells and in a smaller subgroup of invasive breast cancer cells. Recent research has shown that the interaction of psoriasin with the signaling protein Jab1 may be a keystone of the signal network of the breast cancer cell, and that psoriasin binding can cause Jab1 to stimulate the development of invasive and metastatic breast cancer cells. Inhibiting protein-protein interactions is an exciting new approach in the search for targeted cancer therapeutics, and the psoriasin-Jab1 interaction is a promising new target for the treatment of breast cancer. Dr. Fraser Hof’s work deals with fundamental questions about the interactions of proteins and small molecules and with the applied design of small molecule therapeutics. His proposal is to design and develop novel drug molecules to block this psoriasin-Jab1 interaction, first to validate the target and then to guide subsequent drug development. A drug that inhibits this interaction may offer a novel therapy to directly target pre-invasive breast cancer and prevent the development of invasive breast cancer. This therapy may also hold promise as a new approach to target the small subgroup of invasive breast cancers where psoriasin is also present, as this subgroup is typically not eligible for current targeted therapies such as tamoxifen and herceptin.
Dopamine mechanisms of reward learning and cognitive control in children with attention deficit hyperactivity disorder
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.
Social Determinants of Rural and Northern Community Health
Research has increasingly linked the health of individuals to the integrity of a community’s social fabric, the extent to which residents in a community trust each other and participate in community activities, and on the networks of communication and exchange between community members. However, little research on this “”social capital”” has been conducted in British Columbia. Yet, communities in British Columbia are facing an accelerated pace of structural change due to the effects of globalization, changes over the past 15 years in health and welfare systems, and industrial restructuring. It is imperative, particularly in the Central and Northern Interior of the province, where an unprecedented eco-economic crisis is unfolding due to the pine-beetle infestation, that the impacts of these changes in community structure and functioning and, in turn, their impacts on social capital and the health and the health and educational status of children and adolescents are investigated in a way that may lead to amelioration. Building on the foundation of over a decade of work on the social determinants of workplace and community health and a recently awarded New Emerging Team grant to investigate the social determinants of community health in British Columbia, this program of research will further methodological developments in community health research while strengthening the base for community health research at the University of Victoria, in BC, nationally, and internationally. Given that many other communities in Canada, as well as in other nations, similar challenges, the knowledge, conclusions, and recommendations arising from this program of research will be applicable in other jurisdictions.
Timely Access to End-of-life Care for Patients with Life-threatening Illness
The goal of this study is to ensure patients with cancer and other fatal illnesses receive the right kind of end-of-life care at the right time and in the right place. For this to be possible, it is essential to improve the ability of clinicians to accurately assess how long these patients will live because their expected length of survival is a key factor in determining the types of care they will receive. In a research project involving one palliative care program in BC and two in Alberta, this team is assessing the extent to which health data that is collected routinely during initial and follow-up assessments can improve the accuracy of survival estimates.
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Bereaved family caregivers’ adjustment to loss: developing evidence to support healthy adjustment
Providing care for someone with a life threatening illness is a difficult job that taxes family members’ emotional and physical resources. Changes in the health care system have increased the amount of care family caregivers provide at home, with the result that many are caring for a loved one seven days a week for weeks and months. About half of these family caregivers report chronic illnesses of their own, and up to a third have symptoms of depression. Painful emotions experienced by family caregivers can worsen when the ill person dies. Bereaved family caregivers suffer from exhaustion and emotional distress, and are at risk for developing health problems, including illness, insomnia, anxiety and depression. Even the most resilient people experience significant distress in the early months of bereavement. Health care providers do their best to respond to bereaved family caregivers’ needs, but little is known about what helps to foster adjustment in bereavement or when particular interventions would be most useful. Moira Cairns is asking bereaved family caregivers what they find helpful and unhelpful, with the goal of determining what types of care and support health professionals can offer to reduce physical, mental and social health risks and promote healthy adjustment among bereaved family caregivers.
Phenotypic Rescue of Neuronal Structure and Function in a Rett Syndrome Mouse Model
Rett syndrome is a debilitating neurodevelopmental disorder that affects between one in 10,000 to one in 15,000 females. Symptoms that appear in early childhood include severe mental disabilities, impaired speech and movement, and seizures. Individuals with Rett syndrome show abnormalities in the size and structure of certain neurons in the brain. At present, there is very little treatment available for this disease. In most patients, Rett syndrome is caused by mutations in a single gene called MECP2. David Stuss’ research is part of a collaborative effort that is investigating methods for introducing a functional form of this gene into the brain at the appropriate developmental stage. This is expected to allow neurons to follow their normal course of growth and maturation. The methods being developed use engineered lentivirus vectors that are capable of delivering genetic material into differentiated, non-dividing cells like neurons. These viral vectors can also introduce genes for fluorescent proteins into targeted cells at the same time, allowing detailed microscopic visualization of the effects of treatment on neuronal structure. If the rescue of neuronal structure and brain development following therapeutic gene transfer can be demonstrated, this research will be an important first step in creating a therapeutic strategy for treating the devastating effects of Rett syndrome in children.
First Nations Women Leaders: Building a Bridge from Cultural Identity to Healthy Youth
In British Columbia, First Nations youth are five to 20 times more likely to die by suicide than their non-Aboriginal peers. These youth suicide rates, however, are not uniformly high across the almost 200 First Nations communities in BC. Research has found that suicide rates are lowest in those communities that have been especially successful in preserving and promoting their cultural heritage and in securing local control over key aspects of community life. More recently, it has been found that suicide rates are lower in communities where women actively participate in their local government. Robin Yates is exploring the relationship between First Nations women leaders, cultural identity, and lower suicide and injury rates of youth in BC First Nations communities. The results of her research will enhance the development and exchange of knowledge regarding factors that preserve and promote healthy youth in First Nations communities.
Mapping the combinatorial code that generates bipolar cell diversity in the retina and identification of candidate human ocular disease genes
The retina is a thin sensory structure that lines the inside of the eye. Visual information is captured in the retina by cells called photoreceptors which convert the energy of light into electrical signals. Prior to the transmission of signals to the brain, visual information is processed through a class of cells found in the inner retina, the retinal interneurons. These retinal cells integrate and modulate the signals received by photoreceptors and relay the processed information via ganglion cells to the brain. Without retinal interneurons, we would be unable to process visual information and consequently, we would be unable to see. Very little is known about the birth and development of the bipolar cell class of retinal interneurons or the contribution of this cell class to visual disorders. Recent work has determined that visual pathway dysfunction is one of the leading causes of visual impairment, highlighting the need for biomedical research in this area. Erin Star’s research is focused on deciphering the molecular mechanisms that generate and regulate the formation of the bipolar cell class of retinal interneurons. Knowledge gained through this research will contribute to our understanding of fundamental retinal biology, and it is anticipated that ultimately this research will provide the insight necessary to address and effectively treat inherited disorders of the visual system.
Dissecting the Modular Structure of the Secreted Glycoside Hydrolase Exotoxins of Clostridium perfringens: Catalysis and Carbohydrate Recognition
Clostridium perfringens is found ubiquitously throughout the environment, present in soil, and the gastrointestinal tract of animals. When people eat improperly cooled food contaminated with C. perfringens, toxins are produced in the intestinal tract causing the symptoms of food poisoning. In developing countries necrotic enteritis, or pig-bel may develop, a life-threatening disease that attacks the intestines. The bacterium also causes the severe medical condition gas gangrene where, once infected, the progression of the disease is very rapid and often results in fatality. Elizabeth Ficko-Blean is studying the mechanism by which two toxic enzymes, secreted by C. perfringens, are involved in the ability of the organism to cause disease. Elizabeth wants to determine whether the toxins enable the bacterium to spread infection in a wound and degrade human tissues. The findings may contribute to the development of new drugs to inhibit these enzymes, decreasing their toxic effect, and allowing antibiotics more time to fight the progression of the bacteria.