Melanoma is the most dangerous type of skin cancer. The incidence and rate of death from melanoma is rising in Canada. Since 1988, the death rate from melanoma increased 41% in men and 23% in women, which is the highest rate of increase for any type of cancer. Melanoma is primarily caused by repeated sun damage, which leads to the accumulation of mutations in the genes that regulate the survival and growth of pigment cells in the skin. The disease has a molecular basis, so it only makes sense that a molecular approach is being taken to find new therapies to treat this deadly disease. Dr. Catherine Van Raamsdonk is taking a unique molecular approach to identify genes that may be involved in melanoma. By studying three mouse strains that have a darker dermis (the lower-most layer of the skin), Dr. Van Raamsdonk and her colleagues have discovered three genes named GNAQ, GNA11 and NF1 that are important for pigment cell growth and survival. By studying how these genes interact with each other and how they are regulated at different stages of development, she hopes to understand how they may contribute to melanoma. This work will help to reveal the molecular basis of melanoma as well as other cancers. For example, the NF1 gene is also mutated in human neurofibromatosis, a genetic disease in which patients develop disfiguring tumors and hyper-pigmentation of the skin. Dr. Van Raamsdonk and her colleagues have also discovered that GNAQ and GNA11 are mutated in 78% of human uveal melanomas, the most common type of eye cancer. This breakthrough is significant because the mutations associated with uveal melanoma were previously unknown. Dr. Van Raamsdonk is the only professor in the world examining the role of GNAQ and GNA11 in mouse pigment cells, making this work unique and essential. The information she gains may be used to prevent, diagnose, and treat different types of cancers, including melanomas.
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Treatment of drug-resistant influenza: Rationally designed inhibitors of viral neuraminidase
Each year the influenza virus infects approximately 10% of the human population, resulting in hundreds of thousands of deaths. Even in North America, nearly 40,000 annual “excess deaths” are attributed to influenza or to secondary bacterial infections. Despite a World Health Organization-monitored vaccine program, the disease remains a significant global health issue, requiring the use of antiviral drugs like oseltamivir (Tamiflu). A significant problem in controlling the spread of influenza is the emergence of oseltamivir-resistant strains.
To address this problem, Dr. Jeremy Wulff is taking a collaborative approach to develop potent new influenza virus inhibitors. With Professor Martin Boulanger's group at the University of Victoria Department of Biochemistry, Dr. Wulff has developed a new class of antiviral agents that function by a similar mechanism to oseltamivir. His research group is working to further improve the efficacy of these agents through structural and kinetic means. Finally, Dr. Wulff will test the potency of the new anti-influenza compounds in collaboration with Dr. Terrence Tumpey, from the U.S. Centers for Disease Control in Atlanta.
Identifying and developing new drugs to fight oseltamivir-resistant influenza is anticipated to have wide-reaching impacts on global health. In addition to creation of new influenza drugs, Dr. Wulff’s research interests include the development of novel methodologies for the synthesis of complex molecules, and the invention of new kinds of inhibitors that specifically block interactions between certain proteins involved in pancreatic cancer and HIV.
Investigating the structure and function of the PIKK family of protein kinase
Many major chronic diseases, including cancer, Type 2 diabetes, and neurodegenerative disorders, are caused by perturbations in the internal communication network of the cells within the body. Signaling molecules, which are an important part of the intracellular communication network, coordinate different processes by relaying signals to switch on or off the proper sets of cellular machineries at the appropriate time. By understanding how these signaling molecules work, scientists hope to understand the molecular basis of different diseases and how to treat and prevent these diseases.
One important group of signaling molecules are the PIKK kinases. PIKK kinases are responsible for regulating cell growth and initiating responses to DNA damage, processes that are often disrupted or exploited in cancer formation and progression. Although recent research has identified the different proteins and protein complexes that PIKK kinases receive signals from or transmit signals to, exactly how these communication events occur at the molecular level remains poorly defined.
Dr. Calvin Yip's research program aims to understand the role of PIKK kinases in cancer progression. He is characterizing the three-dimensional structural and biochemical details of these molecules using an advanced imaging technique known as single-particle electron microscopy. Dr. Yip has obtained the first information on the 3D shape of a signaling complex formed by TOR, a member of the PIKK kinase family. With this foundation, he will use an interdisciplinary approach to combine cutting-edge electron microscopy technology and other biochemical and molecular biology methods to further determine how the TOR signaling complex receives and integrates information and how it sends signals to its targets.
Dr. Yip hopes that by focusing on how TOR and other PIKK signaling molecules carry out their biological activities, he will gain a deeper understanding of the fundamental processes of cell growth regulation. This will help pave the way for the development of new therapeutic approaches against cancer.
Balancing immunity and inflammation in the intestine
The human gut is a unique environment, simultaneously tolerating an endless variety of food particles and billions of helpful bacteria while retaining the ability to recognize and respond to potentially dangerous infectious diseases. In the developing world, gut infections such as cholera, amoebic dysentery, and parasitic worms are the leading causes of disease and death and are a major burden on development. Gut inflammation is also involved in inflammatory bowel disease and colorectal cancer. More than 200,000 Canadians suffer from inflammatory bowel disease (one of the world's highest incidence rates) and each year more than 22,000 Canadians will be diagnosed with colorectal cancer.
Dr. Colby Zaph studies mouse models of intestinal infection and inflammation in the gut in order to identify and understand the molecules and cells that regulate the balance between immunity and inflammation. His unique approach is to study the immune responses that develop after the gut is infected with a worm parasite called whipworm (Trichuris), which infects more than 800 million people globally.
Dr. Zaph hopes that his work will aid in understanding how the body knows it is infected (sensing), how it kills the invading organisms (inflammation), and how it turns off the response to stop inflammatory diseases from developing (resolution). The results from his research will hopefully identify pathways and targets that can both promote protective immune responses and eliminate inflammatory diseases of the intestine, including infectious diseases, inflammatory bowel diseases, and colorectal cancer.
Placements for Learners
GET Prog for Acute Care Nursing
Enhancing Education Capacity
Innovation in Clinical Nursing
An investigation of cognitive behavioural therapy, mindfulness, and predictors of psychological treatment response among women with provoked vestibulodynia
Provoked vestibulodynia (PVD) is severe pain at the vaginal opening and the most common form of chronic genital pain in women. Although as many as 14 per cent of Canadian women and 20 per cent of adolescents are affected by this condition, it is frequently underdiagnosed and undertreated, and as a result, many women experience sexual difficulties, emotional distress, and multiple medical visits. Although different types of treatment exist, ranging from medication to psychological therapy, the best treatments to reduce PVD pain and distress, and which patients will benefit the most, are not known. Evidence indicates that psychological therapies such as cognitive behavioural therapy (CBT) and mindfulness-based therapy (MBT) are effective at reducing pain and sex-related distress for women with PVD. CBT is designed to challenge thoughts and uses active strategies (e.g. progressive muscle relaxation to decrease muscle tension) to change one’s experience, whereas MBT teaches individuals to be nonjudgmental and accepting of their experience and to learn to live without reacting to pain. Dr. Kelly Smith’s aim is to determine whether CBT or MBT is the most effective approach for reducing PVD pain and improving women’s quality of life, and she will determine which patient characteristics are associated with better responses to these treatments. She will be examining personal and medical characteristics for women with PVD who participated in the Multidisciplinary Vulvodynia Program, a treatment program based at Vancouver General Hospital for women with chronic genital pain. She will then study whether CBT or MBT is related to greater pain reduction and improvements in sexual function/emotional distress in a group of 70 women participating in an 8-session CBT or MBT group program. At the end of the study, women will be interviewed to assess their satisfaction with the program and provide feedback on how to improve the program. Dr. Smith’s studies will be the first to provide information on which of these psychological treatments works best for specific types of women with PVD. This information will provide clinicians with evidence-based guidance regarding potential treatment recommendations and will be essential in helping to reduce the health and economic burdens associated with PVD. Dr. Smith’s final results will be communicated to physicians and other health providers in British Columbia, and her findings will be submitted for publication in professional, wide-reaching health journals.
Socioeconomic status as a predictor of prenatal mental health, use of selective serotonin reuptake inhibitors during pregnancy, and infant outcomes
During pregnancy, approximately 15 per cent of women experience depression requiring medical intervention. Although these conditions are often treated with Serotonin Reuptake Inhibitor (SRI) antidepressants, these drugs are reported to increase the risks of adverse infant outcomes, including preterm birth, small for gestational age (SGA) birth, respiratory distress, and some congenital heart malformations. Infant outcomes are also influenced by other factors, including socioeconomic status, and research has shown that mothers of lower socioeconomic status are at increased risk of preterm birth, SGA birth, stillbirth, and neonatal and infant death. To complicate things further, data shows that mothers of low socioeconomic status are significantly more likely to experience depression during pregnancy and are significantly more likely to use one or more psychotropic medications (including antidepressants) to manage mental illness during pregnancy than women of higher income. The relationships between prenatal depression, socioeconomic status, use of antidepressants, and infant outcomes are complex and poorly understood.
Dr. Gillian Hanley will systematically address questions about the role socioeconomic status plays in maternal depression, antidepressant use, and infant developmental outcomes during the first year of life. She has hypothesized that maternal socioeconomic status accounts for an increased risk of adverse infant outcomes previously attributed to antidepressant exposure during pregnancy. For this study, Dr. Hanley will link a number of BC population-level administrative datasets to build the most comprehensive source of data on pregnant women of its kind in the world. This dataset will include all pregnancies and births in British Columbia between 2002 and 2009 (approximately 300,000 infants) and will provide sufficient sample size to detect differences in rare outcomes, such as congenital anomalies and neonatal/infant death. In this project, socioeconomic status will be studied as a predictor of antenatal maternal depression, antidepressant use, and infant developmental health.
These results will illuminate complex relationships between prenatal depression, antidepressant use, and infant outcomes. Given that it is ethically and medically unadvisable to undertake a randomized trial of prenatal antidepressant exposure, this population-based study will provide an unprecedented opportunity to examine key influences on infant health. Dr. Hanley's findings should help clinicians and mothers make more informed treatment decisions for their health and that of their infants.