Canadians, like other people living at higher latitudes, often experience seasonal changes in sleeping patterns, appetite, mood, and energy levels between the winter and summer seasons, but there has been little research to explain why. Fern Jaspers-Fayer is studying the impact of season on thoughts, moods and behaviour. These changes occur along a continuum from normal to abnormal, with severe winter depression, or Seasonal Affective Disorder (SAD), at one extreme. Fern is identifying the changes in electrical brain activity associated with SAD, and will determine whether these changes disappear in the summer. The results should help explain the brain mechanisms involved in SAD, leading to better therapies for the condition and better ways for everyone to chase away the winter blues.
Program: Trainee
Somatic and gametic loss of imprinting (LOI) in mammalian development: studies using a novel imprinted transgene on the mouse distal choromosome 7 (MMU7) imprinted region
Genetic inheritance in an offspring primarily results from the interplay of dominant and recessive genes between two parents. With certain genes, however, gene expression is parent-of-origin-specific: these genes will always be expressed from either the maternal or paternal chromosome. This process is known as genomic imprinting, which creates a mark, or “imprint”, on the chromosome. Loss of imprinting (LOI) is often studied in the context of disease, especially in cancers, but it is also a normal part of development. For example, in germ cells, imprints are erased and re-set early in development every generation, resulting in a normal period of LOI. Meaghan Jones is investigating a hypothesis that non-germ cells may also experience some normal LOI during development. She will examine the timing, stimulus and duration of LOI in germ cells and somatic cells during development. By determining the various causes of LOI in both types of tissues, she hopes to uncover factors regulating normal LOI and help alleviate the risk of imprinting defects.
Notch signalling in mammary tumorigenesis
Breast cancer is the most common cancer among Canadian women. One in nine women is expected to develop breast cancer in her lifetime, and one in 27 will die of the disease. Metastasis, or the spread of the tumour to another site, is the major cause of death. Notch receptors are cellular proteins required for normal growth and development. However an overproduction of an active component of Notch can cause abnormal cell growth, leading to tumour formation and the spread of cancer to distant sites. Iva Kulic is examining how another protein, called Slug, functions with Notch to promote breast cancer. Both Notch and Slug are found at high levels in some human breast cancers and are a sign of poor outcome. Slug prevents tumour cells from dying and allows them to detach from neighbouring cells and travel to other sites within the body – two key features in tumour development and metastasis. This research will explore whether reducing or eliminating the Slug protein will inhibit breast tumour growth and block the spread of cancer cells. Resolving whether Slug is essential in Notch-induced breast cancer could lead to new ways of preventing and treating the disease.
Death anxiety and spousal caregiving of persons with dementia
Persons with a dementing illness such as Alzheimer disease are often cared for at home by family members. Caring for someone with Alzheimer disease can be a stressful and challenging experience. Death anxiety (the fear of death or the dying process) is one issue that has received little attention in research on family caregivers of persons with dementia. As a person with Alzheimer disease may die within years of receiving this diagnosis, a family member may experience death anxiety through fear of watching the person they care for die, or fear of dying while the person with dementia still needs their support. Anthony Kupferschmidt is seeking to understand the degree to which family caregivers of persons with dementia experience feelings of death anxiety and the effect of these fears on their health and ability to cope and continue in their caregiving role. Findings from this research could ultimately contribute to improvements in education and other community-level programs to better support caregivers of persons with a terminal diagnosis. Anthony is also the 2006 recipient of the Canadian Association on Gerentology Margery Boyce Bursary. This award supports post-baccalaureate students who have made a significant contribution to their community through volunteer activities with or on behalf of seniors and who are registered in a program of study focused on aging or the aged. This prestigious award is the only national award available to gerontology graduate students that is not granted on the basis of financial need.
Activation of NR2A-containing NMDA receptor-mediated cell survival as a novel and innovative therapeutic strategy in the treatment of stroke
Stroke is a major cause of death and disability in North America. Major efforts have been placed into blocking mechanisms of excitotoxicity following stroke. Immediately after the onset of stroke, a plethora of glutamate is released in the affected area, and activation of NMDA-receptor by glutamate has been attributed to be the main cause of neuronal damage during stroke. Nevertheless, clinical studies of stroke patients given NMDA-receptor blockers have proven to be disappointing. It has been suggested that NMDA-receptor blockers are efficacious only when given prior and/or soon after stroke onset. Once the receptors and downstream death signaling cascades are activated, blocking NMDA-receptor is no longer useful. Since stroke patients often reach the hospital and receive their diagnosis several hours after stroke onset, the conventional therapeutic strategy of blocking NMDA-mediated cell death is not clinically useful. Surprisingly, our preliminary study suggested that only the NR2B subunit-containing NMDA-receptors (NR2BR) promote cell death, and paradoxically, the NR2A subunit-containing NMDA-receptors promote cell survival (NR2AR). We propose that selective activation of NR2AR-dependent cell survival may be a more effective stroke treatment strategy than blocking NR2BR-dependent cell death. In addition, because we are proposing to promote cell survival and not blocking cell death, our treatment should be effective even when administered along time after stroke onset.
Computational characterization of genomic islands and their origins
Bacteria are the most abundant type of life on earth and are constantly adapting to survive in different environments. The species we see today are highly diverse, reflecting adaptations to massive environmental changes over billions of years. Some adaptations are of significant medical concern because they result in new strains of disease-causing bacteria, greater virulence in existing bacteria, and increased resistance to antibiotics and other drugs that kill or suppress bacteria. These bacterial adaptations are associated with “genomic islands,” clusters of genes the bacteria appear to have acquired from other bacteria, viruses and organisms. The genes of hundreds of disease-causing and non-infectious bacteria have been identified. Morgan Langille is using this information to develop a database of bacterial genomic islands. He aims to identify the origins of bacterial genomic islands and their role in causing disease. This information may enable scientists to better understand and develop new drugs that target infectious disease-causing bacteria.
The Determination of Accessibility to and Utilization of Fair PharmaCare by Various Ethnic Minority Groups
Since the mid-1990s, North American prescription drug expenditures have been escalating at double-digit rates. Canadians spent $18 billion on prescription medicines in 2004. The rising cost of prescription drugs has raised concerns about the affordability of health care for Canadians. Provincial drug coverage programs within Canada employ diverse strategies for reimbursement. In British Columbia, an income-based drug benefit plan is utilized. This program, dubbed Fair PharmaCare, requires residents to register with the government to be eligible for public subsidy. Vivian Leong is evaluating levels of participation in the Fair PharmaCare program in different socioeconomic and socio-cultural communities to determine the factors that influence access among ethnic minorities. Vivian will identify whether some groups have unequal access to pharmacare subsidies, and if so, why the inequity exists. She is also assessing whether provincial government efforts to promote awareness among minority groups have been effective. This research will help policy makers address inequities and target health promotion to reach and better serve various ethnic communities in British Columbia.
Femoroacetabular impingement as a predictor for Osteoarthritis of the hip
Osteoarthritis (OA) is a debilitating disease characterized by the degeneration of cartilage. OA is a common disease among the elderly, affecting more than three-quarters of people over the age of 75. Research has suggested a link between the development of OA and femoracetabular impingement syndrome (FIS), a disease of the hip. In FIS, the femur makes contact with the acetabulum (the cup-like recess in the pelvis that acts as the socket in the joint), causing pain. This is most evident during periods of extreme range of motion and often occurs due a structural abnormality of either the femoral head or the acetabulum. Early detection of FIS has the potential to allow doctors to alleviate or arrest the onset of osteoarthritis. However, radiographs, which are the current standard of diagnosis, have limitations. Joshua Levitz’s research seeks to develop a better way to diagnose FIS. His study involves creating computerized, 3-D bony models of hips from MR images, to study hip alignment in both subjects diagnosed with FIS and healthy control subjects, and determine the significant factors characterizing FIS. By developing a more sensitive gold standard for diagnosing FIS, this research may provide a method for early prediction of OA.
Gold Nanoparticle-Conjugated Antibodies as Optical Contrast Agents for In Vivo Molecular Imaging of Cancer
Cancer is the leading cause of premature death in Canada, and the number of new cases continues to rise as the population grows and ages. Based on current rates, 38 per cent of Canadian women and 44 per cent of Canadian men will develop cancer in their lifetimes, many when they are 70 or older. Traditionally, physicians assess the severity of cancer tumours by removing tissue samples from a patient and assigning a severity score based on what they see under the microscope. This process can be time-consuming and yields limited information. Recent discoveries have identified a number of molecules produced by cancer cells. Gerald Li is working on an optical imaging system to detect and evaluate the presence of these molecules. In particular, his focus will be on the use of specially designed probes that will flag these molecules, allowing a physician to immediately identify malignant cells. This system will make it possible to image various parts of the body to detect cancer earlier, predict which pre-cancerous lesions will become tumours, and image tumours in the operating room to help determine the boundary between healthy and malignant cells. It will also assist in the selection of treatments targeting cells that create these molecules.
Mechanistic approaches to androgen-independent prostate cancer
Prostate cancer is the main form of cancer affecting men in the western world. Because cellular mutations within the prostate are regulated in part by androgens (male sex hormones), treatment of prostate cancer usually involves starving the prostate of androgens. While this therapy initially stops cancer progression, over time, the cancer continues to progress. Jennifer Locke is researching why prostate cancer progresses despite the apparent lack of androgens during treatment for the disease. Jennifer is testing the hypothesis that new androgens are produced within the prostate during androgen-deprivation therapy, causing the cancer to reoccur. Using molecular and analytical techniques, she is investigating androgen synthesis pathways. This research could enable identification and evaluation of inhibitors of these pathways, which may lead to new therapeutic options. Her ultimate goal is to improve treatment outcomes and quality of life for prostate cancer patients.