Identification of critical gene regulatory domains using bioinformatics and comparative genomics

Over the last ten years, researchers have identified all the genes in our species—approximately 40,000 genes—called the human genome. The mouse genome will be completed soon. It’s estimated that mice and humans shared a common ancestor 70-100 million years ago, and we still share many of the same genes. Dr. Mia Klannemark is using specialized computer programs to compare data on mouse and human genes. She hopes to gain insight into regulatory regions adjacent to genes, which control the production of proteins. Mia is examining how genes make proteins, and identifying which regulatory regions have remained the same between mice and humans, because these genes indicate important functions that have not changed over the period of evolution. She is also identifying genes that have changed, which may contribute to the differences between species. This knowledge will help us understand how genetic variation influences the development of disease, and could lead to more effective treatments.

Susceptibility genes and environmental risk factors in Alzheimer's Disease

Dr. Robin Hsiung is researching the genetic and environmental origins of Alzheimer’s disease. The disease is the most common type of dementia, affecting five per cent of seniors aged 65 and older, and 40 per cent of people over 80. People suffering from Alzheimer’s often need costly treatments and placement in care facilities. Recent advances in molecular genetics have led to the discovery of at least four genes involved in the development of Alzheimer’s disease. However, a number of genes that are believed to be connected to the disease have yet to be confirmed. Robin will examine samples and data from two large Canadian studies of people with Alzheimer’s and other cognitive impairments. His research will identify the genes and environmental risk factors that indicate susceptibility for Alzheimer’s disease. Understanding how these risks can be modified will enable the development of new educational programs and therapies that may decrease the incidence and financial burden of this disease.

Transcriptional regulation of HIV LTR and mechanism of HIV latency and reactivation

Anti-retroviral therapy for HIV typically suppresses the virus in patients’ blood to undetectable levels, enabling people with the infection to live symptom-free. However, some T cells are latently infected by HIV and remain unaffected even by prolonged treatment. These latently infected cells and other lymphocytes pose the major barrier to eliminating HIV infection, and provide a latent reservoir for the virus to reactivate. Long-term anti-retroviral treatment can also cause HIV resistance to therapy in some patients. An alternate strategy is therefore needed to target the latently infected virus and ultimately cure AIDS. Dr. Jiguo Chen is researching how HIV-1 establishes latency and how it reactivates. He and other colleagues in the Sadowski lab have isolated and identified a complex of several transcription factors termed RBF-2 (Ras-responsive element binding factor), which binds to HIV long terminal repeat (HIV-1 LTR) and represses HIV-1 transcription during latency. He believes that this complex plays a role in establishing and maintaining latency. He is using several different experimental strategies to determine the role of RBF-2 and to learn how it works during latency and reactivation, so new drug therapies can be designed to clear HIV from patients’ immune systems.

An evaluation of the full circle project: The effects of a theatre-based HIV prevention intervention on audience and actor/educator learning

What are the best ways to ensure young people listen to and act upon information about avoiding high risk sexual behaviours? This is the research focus for Josephine MacIntosh, who is delving into the individual, social and cultural factors that may perpetuate the epidemics of HIV and sexually transmitted diseases, especially among young women. Josephine is studying the effectiveness of using a theatre-based intervention program among youth aged 13 to 15. The theatre productions will consist of a series of original dramatic productions researched, scripted, produced and presented by youth volunteers. She hopes to develop an educational approach that can engage the audience and actors as they learn about issues such as abstinence, treatment of HIV and sexually transmitted disease, pregnancy prevention, decision-making, peer-pressure, negotiation for safer sex and alternative safer sexual behaviours.

Paracrine processes in prostate cancer progression

Prostate cancer is the second leading cause of cancer-related deaths in men. Advanced prostate cancer is often treated with androgen withdrawal therapy, which blocks the growth-promoting effects of androgens (such as testosterone). Unfortunately, the cancer eventually progresses to an androgen-independent state, allowing for tumour growth without androgens. Dr. Michael Cox is studying how prostate tumour cells with neuroendocrine characteristics contribute to the disease’s progression to androgen independence. His research aims to understand how these cells develop within prostate tumours, what effect such cells have on the growth rate of prostate tumours, and how hormones secreted by these cells influence therapeutic resistance and metastatic preferences during disease progression. Dr. Cox is also working to determine the molecular mechanisms by which prostate tumour cells develop genetic mutations and become less susceptible to cancer treatment. He is identifying how tumour cells respond to growth factors in the presence or absence of testosterone and the cellular changes that allow prostate tumour cells to utilize these growth factors to aid development of testosterone independence.

Investigating the link between symptom expression, medicalization and acculturation: The case of Portuguese immigrants

Dr. James has conducted groundbreaking research into the experiences of Portuguese immigrants with agonias, a commonly-expressed disorder that is literally translated as “the agonies.” While North American clinicians often diagnose agonias as anxiety and/or depression, and treat it with medication and psychotherapy, these approaches are often unsuccessful. Dr. James’ previous research indicates that the meaning, symptoms and treatment of agonias do not match the standard psychiatric disorders of anxiety or depression. Dr. James is investigating the differences in the way clinicians and members of Portuguese communities understand agonias; whether it is related to anxiety or depression; and whether assimilation into North American society changes community members’ understanding and experience of agonias. This research will further inform her work teaching therapists throughout Canada and the US how to conduct psychotherapy with ethnic minority patients.

Evaluation of efficacy of borate-based fungistatic treatments on building materials and growth, pro-inflammatory and toxic products of secondary metabolism by selected micro-organisms

With the prevalence of “”leaky”” buildings in BC, there is increasing awareness of the potential health risks associated with damp building products fostering the growth of fungal organisms. These organisms grow from spores, which are naturally abundant in outdoor air. Although spores cannot grow on dry building materials, they can readily form colonies and grow on building materials that have sufficient moisture (e.g. resulting from water leaks, flooding or condensation). These fungi are thought to contribute to respiratory and inflammatory health problems in people. Dr. Karen Bartlett is studying the effects of a class of anti-fungal preservative containing borate. This preservative, used to inhibit fungal growth on wood products, is not yet approved for use in Canada. Dr. Bartlett is monitoring whether borate leaches out building materials when they are wet and becomes ineffective. She is also investigating whether the fungi produce any harmful byproducts in response to these preservatives that might create further health problems.

Health status and health care utilization among mid-life Chinese, South Asian, and British Canadians in the lower mainland: An examination of socio-economic, immigration, and cultural dimensions

Dr. Karen Kobayashi has long been interested in how ethnicity affects aging and health. In her current research, Karen is comparing the health of Chinese and South Asian adults—the fastest growing ethnic groups in the Lower Mainland—with Canadians of British origin. She is examining differences in health status and use of health services among middle age Canadians to determine the factors that may promote or impede healthy aging. The research involves interviewing participants to determine how differences in such variables as education, income, time since immigration, English language ability, religious affiliation, and adherence to traditional values affect their health status and the way they use health services. She anticipates the research will reveal differences between and within cultural groups. For example, the way foreign-born and Canadian-born adults access health services may vary within each population group. The way new immigrants use health services may also vary from people who have lived in Canada for 10 years or more. This information could be used to predict health care needs among the groups and improve access to health services for these populations as they age.

Endocrine mechanisms of bone mass and structural changes in prepubertal, over-and normal weight Asian and Caucasian boys: Associations with increased exercise and body composition

Based on her previous research on pediatric bone health, Dr. Kerry MacKelvie believes that perhaps the greatest hope for preventing osteoporosis in later life is to intervene during childhood. Kerry has studied how high impact exercise affects bone mass and structural changes during growth, and she has investigated the effects of ethnic background on bone health. Now Kerry is bringing together in one study an investigation of all the factors that may contribute to bone strength during childhood: exercise, hormones, body mass and composition, and ethnicity. She will study Asian and Caucasian boys who have not yet reached puberty, focusing on bone mass changes over time for both overweight boys and inactive boys. The study is particularly relevant to Vancouver’s population, as it will examine and compare ethnic-specific hormonal, body composition and bone mass changes during growth in both Asian and Caucasian children.

Epidemiology, genetics and molecular biology of a virulence-associated bacteriophage of Chalamydia pneumoniae

Dr. Karuna P. Karunakaran is exploring a mystery around how Chlamydia pneumoniae (an infectious bacteria) is implicated in atherosclerosis (hardening of the inside of the arteries). While a strong link has been established between C. pneumoniae and atherosclerosis, 60 to 80 per cent of the adult population is infected with the bacteria with no apparent ill effects. One explanation may be that some strains of the bacteria are more capable of causing vascular disease than others, due to genetic variation. In fact, one strain of C. pneumoniae has been shown to contain a bacteriophage, a virus that infects bacteria and integrates itself into the genetic code. Preliminary studies have indicated a strong association between vascular disease and the presence of this strain. Karuna is studying the biology of the implicated bacteriophage, and hopes to identify the strains of C. pneumoniae that may cause vascular disease. This may lead to effective design of a vaccine to combat vascular disease caused by infectious bacteria.