Youth and women working in Vancouver’s sex industry are among the most marginalized and vulnerable in Canadian society. The persistently high rates of health-related issues, violence, and mortality among sex workers, both in Canada and globally, highlights a desperate need for renewed public health interventions targeting the reduction of harms in this industry. Dr. Kate Shannon is working to investigate the different factors influencing the health and safety of youth and women working in the sex industry in Vancouver. Her team is studying the social (violence, work conditions) and structural (laws, regulations, urban renewal) contexts of sexually transmitted infection (STI) in this population. Specifically, her team is examining the different factors that influence the worker’s negotiating power during transactions and how this influences the risk of HIV/STI acquisition. Her research will involve the study and long-term follow-up of two groups of women: (1) 500 existing and new adult women working in both the street and indoor sex industry; and (2) 250 female youth aged 14 to 20 years who have exchanged sex for money, drugs, gifts, shelter, or other commodities in the previous 30 days. By evaluating and integrating different types of data, including individual mapping and neighborhood environment data (including violence and housing) from publicly available sources, she hopes to identify policies and harm-reducing interventions for this population. This study is among the first prospective studies of sex work in North America. Dr. Shannon’s team possesses a wealth of expertise in observational and intervention research, policy, and sex work. They are uniquely positioned to conduct this study, which aims to directly improve the health of some of the most marginalized youth and women in Canadian society.
Program: Scholar
Optimal Timing of Medical Decisions
Questions regarding the proper timing of various medical interventions arise frequently in health care. How often should people be screened for a type of cancer? How often should patients go for laboratory tests to measure the progress of an existing disease? What is the optimal time to initiate a therapy or to switch therapies when one appears to lose its effectiveness? These are difficult decisions because of the need to trade off costs and benefits under uncertainty. For example, screening too frequently results in high system costs as well as inconvenience (and possibly harm) to the patients being screened. On the other hand, treatment outcomes are almost always better when disease is treated earlier than later. Dr. Shechter’s research program aims to develop and apply advanced analytical techniques from the field of operations research (OR) to aid decision-making in questions of clinical timing. The methodological tools of OR were designed specifically to deal with complex decision-making under uncertainty and have been applied for more than 50 years in a variety of areas. With the growing complexity of medical decision-making and the increasing availability of patient medical data, these techniques have become extremely relevant for seeking cost-effective solutions to health-care problems. Clinical timing decisions alone provide a large class of difficult decisions that are well suited for study using these analytical techniques. Dr. Shechter’s research includes two specific projects that will analyze key timing decisions for patients with chronic kidney disease: 1) when is the optimal time to prepare an arteriovenous fistula for patients who eventually start dialysis?; and 2) how often should patients on the kidney transplant waitlist be screened for conditions that may put them at increased surgical risks should a donation become available? With a 500 per cent increase in chronic kidney disease among British Columbians over the past decade, improvements in treatment and screening policies can result in substantial health benefits to patients province-wide. Dr. Shechter will work closely with frontline decision-makers, including nephrologists and kidney transplant surgeons, to develop and validate useful data-driven decision models to address these questions.
OCD translational multi-modal research program
According to the World Health Organization, obsessive-compulsive disorder (OCD) is one of the top 10 causes of disability. The disorder often begins in childhood and interferes with normal development. This disabling mental illness affects approximately 2 – 3 percent of British Columbians and, although treatable, is often under diagnosed.
The aim of Dr. S. Evelyn Stewart's research program is to improve the lives of BC children and families living with OCD. Her goal is to improve the evaluation and awareness of pediatric OCD in BC by conducting research to guide scientific and clinical understanding of OCD and its management by health professionals, and by establishing national and international linkages, which will lead to future research collaborations. Dr. Stewart's specific objectives for the first five years are to 1) create a unique research program within the new pediatric OCD clinic at BC Children's Hospital that is closely tied with the community, 2) establish a pediatric OCD DNA and research data site for BC, 3) launch a comprehensive patient-assessment method, and 4) investigate the outcomes and effectiveness of the program itself.
This program is unique, as it pulls together expertise from the clinic, the community and the laboratory. One important feature of Dr. Stewart's program is the effective transfer of new information between the clinic and the research lab in order to help the outcomes of practice inform research. Dr. Stewart anticipates this program will help limit the suffering and health-care costs related to OCD. The program is anticipated to develop into the first North American OCD Centre of Excellence.
Childhood lung diseases: Infectious and inflammatory mechanisms
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 and neurofibromatosis: genetic diseases linked by dark skinned mouse mutants
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.
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.
Advanced polymers for transfusion medicine and biology: Novel approaches for therapeutics, cell-surface engineering, biocompatible surfaces and proteomics reagents
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.
Investigating pharmaceutical policies, coverage, and costs
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.