Lungs are for life. Unfortunately, the most frequent long-term illnesses in children and babies are respiratory system conditions. Children's lungs can be damaged in many ways: bacterial and viral infections, asthma, or faulty genes causing thick mucus to accumulate in the lungs of children with cystic fibrosis. Even the oxygen and artificial ventilation needed to sustain the lives of premature babies can cause lasting lung damage. A feature shared by all these serious childhood lung diseases is that some of the damage is caused by activation of the innate immune system, which is an important part of our immune defense network. The innate immune system is like a “double-edged” sword. While innate immunity is essential for keeping us healthy, it can cause excessive lung-damaging inflammation if the activity is not carefully controlled.
To prevent lung damage, Dr. Stuart Turvey is examining the systems that control the activity of the innate immune system. These control elements are known as negative regulators. His team will study these negative regulators in a variety of childhood lung diseases spanning premature babies and lung infections through to asthma and cystic fibrosis. The unique aspect of this project, and of Dr. Turvey's group in general, is a commitment to translational research focused on people with lung disease. This means research results from the lab bench are applied directly to patient care.
Rather than relying exclusively on laboratory (animal or cell) models of disease, Dr. Turvey’s team plans to examine genetic material donated by people affected by infectious and inflammatory lung diseases. The results of this work will be an exciting starting point for gaining a better understanding of the causes of childhood lung diseases and developing new medicines to safely control the damaging inflammation that occurs in the lungs of so many babies and children.
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.
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.
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.
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.
Most simply, biomaterials are materials that interact with biological systems to perform, augment, or replace a function that has been lost through disease or injury. Biomaterials have played a critical role in the advancement of modern medical treatments and are key components in medical devices, equipment, and processes. As some examples, biomaterials are essential for the manufacture of artificial hearts, contact lenses, artificial hips, dental materials, stents, and are involved in drug delivery systems and blood storage bags. While biomaterials based on synthetic polymers are extremely versatile, they also come with significant problems. Most materials were not specifically designed for medical use, and, as a result, issues such as biocompatibility and biodegradation can create serious side-effects such as inflammation, immune reactions, local tissue damage, and ultimately the device rejection. Dr. Jayachandran Kizhakkedathu is working to address these challenges by creating new biomaterials designed specifically for use in biological systems. His research group integrates advanced polymer design and chemistry, biological analyses, and animal models to address this important problem. The knowledge and technologies developed in this program will significantly improve our understanding of how synthetic materials interact with human body. Importantly Dr. Kizhakkedathu hopes that the development of new biomaterials will help to advance medical science by inspiring innovative new treatments for cardiovascular diseases and blood disorders and by creating new diagnostic tools and devices.
Prescription medicines play a key role in the treatment and prevention of disease, as evidenced by the fact they are the second-largest and fastest-growing component of health care expenditures in British Columbia. Dr. Michael Law's research program includes studies on the broad themes of pharmaceutical policies, coverage, and costs. Pharmaceutical Policies. In January 2009, a policy change in British Columbia gave pharmacists the authority to independently modify and renew prescriptions. While this policy was intended to improve patient access to drugs and reduce the already heavy burden on primary care physicians, concerns have been raised about potential negative effects on patient safety due and reduced continuity of care. This policy has not been rigorously evaluated.
Dr. Law is currently studying the effects of this policy change on drug utilization and costs, patient adherence to medication, and the number of visits patients make to physicians and hospitals. Pharmaceutical Coverage. Canadians pay for prescription drugs through a patchwork of mechanisms, including public drug programs, private drug insurance, and out-of-pocket payments. In 2008, private insurers paid $9.3 billion in drug costs, representing 31% of overall expenditure. Despite this, we have little sense for how private health benefits plans are changing in light of tough economic times. He is currently leading an investigation into private drug insurance benefits in Canada. Pharmaceutical Costs.
Dr. Law is conducting a series of studies on pharmaceutical costs. This research includes a Health Canada-funded study investigating the factors related to cost-related non-adherence to prescription medicines, an investigation into generic drug prices in Canada compared to international peers, and a continuation of his past work studying the influence of direct-to-consumer advertising on prescribing of medicines. Dr. Law’s research promises to help inform the future design and refinement of important and controversial pharmaceutical policies, provide insights into the trends in private drug insurance benefits in Canada, and create greater understanding of the influence of drug pricing on compliance. This research has the potential to create important changes in the health care system.
The Human Genome Project, which had the goal of sequencing the entire human genome, took more than 10 years, involved the work of thousands of people and cost more than $1 billion. Today, this same amount of work can be accomplished on a single machine in 10 days at a cost of $10,000, which halves every 18 months. The emergence of this "Next Generation Sequencing" (NGS) technology can reveal the precise genetic mutations that underlie how cancers develop, how they become more aggressive and how they acquire resistance to chemotherapy. A challenge of this technology is the data generated can be voluminous, complex and error prone; a single genome can produce over a terabyte of data.
Dr. Sohrab Shah is developing a new generation of computational tools using machine-learning approaches to improve accuracy and best interpret the large scale NGS data sets. With his clinically focused collaborators, he will then apply these technologies to sequence the tumour genomes from patients with triple negative breast cancer, ovarian clear cell carcinoma, and childhood osteosarcoma tumours — three cancer subtypes that do not respond to standard therapies. They hope to identify and profile unknown mutation patterns — or "mutation landscapes” — in each of these diseases.
These mutation landscapes will help Dr. Shah’s team further understand the biology of these tumours and provide a rational basis for the design of novel therapies to improve patient outcomes. His work will also include studying small populations of cancer cells to determine how they influence patients’ responses to treatment and how they become resistant to chemotherapy — two of the major issues facing oncologists today.
In Canada, health system funding has reached a crisis point. Not only are health care costs continuing to rise, but there are increasing conflicts about how these funds are allocated. Provinces are exploring different policies to improve the safety, efficiency, and efficacy of care, including patient-based payment for hospitals to increase 'volume' of hospital care, targeted pay-for-performance programs to reduce wait times, and alternative payment plans for physicians. While these funding policies are designed to change the incentives of providers and health care organizations, there are few methods to measure whether these policies are actually leading to health system improvements.
Dr. Jason Sutherland's applied research program examines the system-level and patient-level effects of new and existing funding policies. This program of research will help measure how health system expenditures are improving the health of BC’s residents, improving co-ordination between settings, and improving the quality of care. His work will assist policy- and decision-makers to interpret the complex relationships between health funding policies, health expenditures, utilization, gain in health, and health outcomes. This program of health services research has the potential to improve the effectiveness, efficiency, and equity of British Columbia's, and Canada's, health care system. By understanding how policy-makers’ decisions are impacting the health care residents receive, Canada's health system decision-makers will be more empowered to make the best decisions.
Radiotherapy is used for curative and palliative (symptom relief) purposes for patients with cancer, with 30 to 40% of patients receiving radiotherapy during some point in their illness. Wait times for radiotherapy have been shown to lead to poorer outcomes for those treated as part of curative treatment, and to increased suffering for those treated for palliative reasons. Wait times occur either because of equipment and/or staff shortages, or due to resources not being used in the most optimal manner. Demand for radiotherapy fluctuates over time, leading to unpredictable surges in demand that are difficult to meet in a timely fashion.
Dr. Scott Tyldesley is working to improve understand of the root causes of the fluctuation in demand for radiotherapy, and to develop approaches to predict and address demands. He, and his colleagues, are creating a detailed model of the radiotherapy system, which will allow him to simulate current cancer patient flow, and to test proposed improvements to the system. Development of the model will also allow the group to explore how the radiotherapy system can improve how it forecasts demand for services, and how it deploys its resources. These results will be tested in system-wide models and then considered for implementation at the BC Cancer Agency (BCCA). The research team is a unique collaboration between specialists in operations research from the Sauder School of Business at UBC and clinical decision-makers and administrators from BCCA. The results of Tyldesley’s research will directly affect clinical practice for patients with cancer and be transferable to other health care environments.
