Posttraumatic stress disorder (PTSD) is a common consequence of life-threatening traumatic events (e.g., road traffic collisions, military combat, criminal victimization). PTSD is a severe anxiety disorder that often follows a chronic course and is associated with significant disablement. Existing PTSD treatments are only moderately effective and research is needed to find interventions that can improve treatment outcome. One potential method of improving treatment outcome for PTSD is by reducing anxiety sensitivity, which is described as a person’s fear of experiencing the physical sensations that result from anxiety (e.g. heart palpitations, dizziness) and their belief that these sensations will have harmful consequences. Anxiety sensitivity is elevated in PTSD and is associated with PTSD symptom severity. Interventions that directly target anxiety sensitivity have the potential to enhance PTSD treatment outcome. Dr. Jaye Wald is conducting the first controlled study to examine the effectiveness of interoceptive exposure therapy (IE) on PTSD. While this behavioural intervention has been shown to be effective in treating anxiety disorders, its ability to improve the outcome of existing PTSD treatments has not yet been investigated. Dr. Wald will use IE to repeatedly expose individuals to feared bodily sensations, with the goal of eventually reducing their anxiety sensitivity. Results of this research will have important practical implications for the mental health care field and for individuals with PTSD by enhancing understanding of this disorder and ultimately improving its treatment.
Program: Scholar
Notch signaling in Lymphoid Neoplasia
A common theme in cancer is the dysregulation of a normal developmental process that either directly causes cells to grow in an uncontrolled manner, or renders them susceptible to cellular damage that, in turn, leads to uncontrolled growth. One example of this process occurs with a normal cellular gene called Notch, which is inappropriately activated in a large fraction of cases of a certain type of blood cancer called T cell acute lymphoblastic leukemia (T-ALL). During normal development of the immune system, regulated Notch activity is required for formation of mature lymphocytes that protect the body from infection. When activated, Notch promotes the formation of normal T lymphocytes, but if this signal is not turned off in time, these T cells can undergo malignant change and become cancerous. Dr. Andrew Weng is studying the signals that are generated by Notch activation and the context in which these signals are received by the cell. By understanding the role of Notch in cancer development, he hopes to develop methods for manipulating Notch activity to shut down the growth of established cancer cells, and perhaps also to prevent it from occurring in the first place.
Tissue microarray analysis of Type 1 growth factor receptor family expression by human breast and colorectal Cancer: prognostic significance and treatment implications
Breast cancer and colorectal cancer are leading causes of cancer-related deaths worldwide. The identification of specific tumor characteristics that would allow for an accurate prediction (prognosticators) of disease course and response to treatment would represent an important advancement in the management of these common malignancies. Unfortunately, no currently known disease prognosticators are reliable in predicting clinical course, or identifying the treatment that would be of greatest benefit to an affected individual. Recently the detection in some tumours of HER1 and HER2 proteins – members of the type 1 growth receptor family (T1GFR) – have shown promise for helping predict patient outcomes and in determining which tumors respond best to specific therapies. These proteins have also recently been used as targets for newly developed drugs to treat these cancers. The expression of the entire T1GFR family (HER1, HER2, HER3, and HER4) by breast and colorectal tumors, and their potential usefulness in predicting disease outcome and patient response to specific treatment(s) has not been explored. Dr. Sam Wiseman is evaluating the expression of the entire T1GFR family in a group of 4500 breast cancer and 500 colorectal cancer samples to determine its relationship to patient treatment and outcomes. His study will be carried out utilizing tissue microarrays, a methodology that allows for the rapid evaluation of large numbers of tumors for molecular markers. The results of this study may lead to improved disease prognostication, outcome prediction, and therapy selection for people diagnosed with breast or colorectal cancer.
Non-surgical cosmetic procedures: health, body image and aging
Non-surgical cosmetic procedures (chemical peels, botox injections, laser hair removal, injectable fillers) are becoming more common than cosmetic procedures (breast augmentation, face lifts, liposuction). Non-surgical procedures are less expensive than cosmetic procedures and thus accessible to more people. To date, research into the perception and experience of non-surgical procedures, which are often viewed as more acceptable, less intrusive and medically risky, have largely been ignored. Dr. Laura Hurd Clarke is examining the perceptions and experiences of women aged 50+, both users and non-users of non-surgical cosmetic procedures as well as the perspectives of physicians who provide the treatments. She is interested specifically in analyzing the relationship between women’s attitudes towards non-surgical cosmetic procedures and their perceptions of health, healthy living, aging and body image. Results from her research will provide insights into the changing norms and social acceptance of the ‘medicalization’ of age-related appearance and a better understanding of the continued blurring of the relationship between health and beauty in contemporary society.
Molecular characterization of Ahi-1, a novel signaling molecule with an SH3 and multiple WD40-repeat domains, in normal and leukemic hematopoiesis
Because many forms of leukemia originate in blood stem cells, uncovering the changes that occur in these cells is crucial to understanding how these diseases develop and progress. Dr. Xiaoyan Jiang is studying Ahi-1, a newly-discovered oncogene (cancer causing gene) that is involved in murine leukemia development (leukemia in mice) and shows abnormal expression in human leukemic cells, including leukemic stem cells from patients with chronic myeloid leukemia and Sezary cancer cells from patients with cutaneous T-cell lymphoma. Her research team recently found that over-expression of Ahi-1 gene alone can cause leukemia in mouse models and suppression of Ahi-1 gene can normalize its transforming activity in human leukemia cells, a strong indicator that Ahi-1 is likely to be an important new oncogene involved in the development of leukemia in humans. Dr. Jiang’s research will explore the normal function(s) of Ahi-1 in the development of blood cells, and how this is altered when cells become leukemic. This research will also begin to identify new intracellular molecules that interact with Ahi-1 and the cellular and molecular pathways through which these interactions occur. Understanding how and by which pathways Ahi-1 contributes to the development of leukemia may provide important new molecular targets for the development of targeted cancer treatment that will be more effective and have fewer side effects than currently used chemotherapy.
Creation and function of neighborhoods in eukaryotic chromosomes: regulation by SWR1-Com, a desposition complex for histone variant H2A.Z
Chromatin is the complex of DNA and protein material that make up chromosomes, home to the genetic code. The basic unit of chromatin is the nucleosome, a fundamental building block consisting of DNA wrapped around an octamer of histone proteins. A large number of proteins involved in cancer development and the genetic susceptibility to devastating diseases such as Ataxia Telangiectasia (a progressive immunological and neurological disorder) act through modification of chromatin structures and interfere with normal chromatin function. Differences in chromatin structures between adjacent regions specify the properties of larger macrodomains called neighbourhoods. The shape and structure of these neighbourhoods influence chromosome behavior, while complex regulatory mechanisms that ultimately involve chromatin ensure that each cell expresses only the appropriate genes, duplicates its genome with high fidelity, divides only when required, all while combating constant assaults on its DNA. Failure in any of the mechanisms regulating these events can lead to disease. These chromatin structures themselves can also be inherited, creating an additional complex set of influences that are crucial for the identity and activity of the cell. The molecular biology of chromatin structures and their role in chromosome biology and genome function in health and disease is the focus of Michael Kobor’s research. Specifically, he is studying a unique chromosomal neighbourhood containing a specialized histone variant known as H2A.Z, which is deposited into chromatin by a large protein complex. Using innovative genome-wide approaches, Dr. Kobor’s team aims to uncover the rules and principles of histone variant function.
Pharmacist identification of new, diagnostically confirmed osteoarthritis (PHIND-OA)
Knee osteoarthritis is the most common cause of disability in older adults. There are three million Canadians currently afflicted with this condition, and it’s predicted that this number will increase by 50 per cent by 2020. The costs of medical care, drugs, and lost wages resulting from this disability is a major economic burden in Canada. Several research studies have demonstrated the benefit of non-drug therapy such as education and exercise for people with knee osteoarthritis. However, many individuals remain undiagnosed for their condition and don’t receive appropriate interventions. Dr. Carlo Marra is researching the potential of pharmacists, who are highly accessible health care practitioners, to help identify people with knee osteoarthritis by using a simple screening questionnaire. Next, he will investigate whether pharmacists can initiate an intervention that brings together patient, physiotherapist, and family practitioner to improve physical function, minimize pain, and reduce the economic burden of this disease. In addition, regular follow-ups will occur to assess and encourage compliance with the intervention, assess outcomes and answer any questions. Dr. Marra anticipates his research will demonstrate the value of this innovative, cost-effective strategy to improve outcomes and quality of life for people with knee osteoarthritis.
Primary health care for Chinese and South Asians: continuous, accessible, and timely
Recent years have seen increasing concern about access to and quality of primary health care in Canada. A substantial amount of provincial and federal funding has gone into revitalizing the primary health care system. The current tools used to assess how the primary health care system works for consumers (such as questionnaires) were originally developed primarily with well-educated, English-speaking Whites of European descent. British Columbia is home to the second largest immigrant population in Canada, where approximately 50 per cent of all BC immigrants are from Asia and one in every ten cannot speak, write, or understand English. Currently, little is known about whether current assessment tools are valid across different ethno-cultural groups who may not speak English. In addition, existing assessment tools may not adequately reflect the issues and concerns about primary health care that are important to different ethno-cultural populations. Dr. Sabrina Wong is studying the dimensions of primary health care that are important to adults from two of the largest ethno-cultural groups living in BC: Chinese and South Asians, who speak Cantonese or Punjabi, respectively. Through focus groups and telephone surveys, she is identifying what dimensions are addressed in existing assessment tools, and what needs to be modified for these ethno-cultural groups. Ultimately, Dr. Wong hopes that her research will result in an assessment tool of primary health care that is equally valid and reliable across English, Cantonese, and Punjabi speaking populations.
Neuroendocrine Regulation of Aggressive Behaviour and Adult Neuroplasticity
Steroid hormones have profound effects on human physiology and behaviour. They are critical for the nervous system to develop and function normally, and play a role in psychiatric and neurological diseases. The levels of one steroid hormone, DHEA (dehydroepiandrosterone), drop dramatically as people age. DHEA supplements have been promoted in the media as a “fountain of youth” that can reverse brain aging and cognitive decline. However relatively little is known about the actions of DHEA on the nervous sytem and how DHEA acts at the cellular and molecular level. In earlier research, Dr. Soma showed that DHEA increases aggressive behaviour and the size of specific brain regions. Now Dr. Soma is further clarifying the effects of DHEA on behaviour and neuroplasticity (the brain’s natural ability to form new nerve cells and new connections after a change in the environment). He is assessing whether DHEA must be converted to sex steroids such as testosterone and estrogen to affect the brain. The research could improve understanding of the physiological functions of DHEA in humans, and help determine how DHEA treatment could be used to alleviate mental illness and increase neuroplasticity.
Regulation of the BACE gene expression in the Alzheimer's disease pathogenesis
Alzheimer’s disease is the most common neurodegenerative disorder leading to dementia. The disease affects about 10 percent of people over the age of 65, and prevalence increases with age. Approximately $5.5 billion is spent in Canada each year on people with Alzheimer’s and related dementias. Deposits of the amyloid ß(Aß) protein in the brain are a characteristic feature of Alzheimer’s. Four genes, including APP, have also been linked to the disease. Processing of APP by the BACE enzyme is essential to generate the A-beta protein. In previous research Dr. Weihong Song made important discoveries about the role of presenilin proteins in the development of Alzheimer’s Disease. Now Dr. Song, who holds the distinction of being the youngest physician to graduate in China, is researching the role of BACE in the development of Alzheimer’s Disease. The research could contribute to development of BACE inhibitors, which could improve treatment of Alzheimer’s.