Nine out of ten Canadians who are killed by cancer die because their tumour has metastasized, or spread, to other parts of their body. Metastasis occurs when tumour cells escape from the original, or primary, tumour and then grow into life-threatening metastatic tumours in other organs. Despite the fact that thousands of tumour cells can escape from a primary tumour every day, most cells do not live long enough to grow into metastatic tumours. As well, metastatic tumour cells can only grow in specific organs. Most primary tumours contain cells at lower oxygen levels than normal tissues, and these low-oxygen tumour cells make tumours more aggressive and metastatic.
Based on these facts, Dr. Bennewith's team is developing new approaches to help identify tumours that contain low-oxygen tumour cells in patients. In addition, Dr. Bennewith and his colleagues have recently discovered that proteins made by low-oxygen tumour cells cause the body's normal bone marrow cells to enter the bloodstream and build up in specific organs. These cells create an environment where metastasizing tumour cells can survive and grow into metastatic tumours. Dr. Bennewith’s team intends to identify the specific proteins that control bone marrow cell behavior in order to develop targeted therapies that will prevent the build-up of bone marrow cells in organs and thus inhibit metastatic tumour growth. Metastatic tumours are very difficult to treat, but by studying how tumour cells spread and grow into tumour metastases, more effective cancer treatments can be designed. Dr. Bennewith's expertise in metastasis research combined with his unique research program will improve our understanding of how low-oxygen tumour cells promote metastasis. Importantly, his work will help to create more effective methods to both detect and to treat metastatic cancer in the clinic.
Informal caregiving is defined as care provided by family and friends to a relative or friend residing in a long-term residential care (LTRC) situation. The role of informal caregivers is significant. Informal caregivers contribute more than 44 million hours of care work in LTRC facilities each year; a number that will more than double to 107 million hours in 2038 (source: Canadian Alzheimer Society). These contributions are essential given the current pressures on LTRC, which include an increasingly acute and medically/socially complex resident population and staffing levels that are typically below industry standards. Dr. Jennifer Baumbusch is conducting a series of studies focused on understanding how informal caregivers currently participate in LTRC. Dr. Baumbusch is asking the following research questions in order to better understand the role of informal caregiving and to develop and refine policies and practices to improve the integration of informal caregiving in LTRC. In what ways do informal caregivers contribute to the care of their relative? In what ways do informal caregivers contribute to the care of other residents? How do the informal caregivers’ contributions affect the everyday facility routines, such as recreational activities and meal times? Research will take place on regular units and on Special Care Units for residents with Alzheimer disease and related dementias and will recognize the unique needs of this specialized population. This program will incorporate ethnographic approaches and will be guided by input from community stakeholders. Research findings will be consolidated with existing literature to provide the basis for knowledge translation activities which will include policy forums that foster a national dialogue about caregiving in LTRC, collaborative knowledge translation research, and arts-based knowledge translation approaches. The aim of this program is to improve the integration and recognize the unique contributions of both informal caregivers and formal caregivers (staff) to care provision. Generating new policy directions will contribute to more effective healthcare services within LTRC and will ultimately improve the health of aging Canadians living in LTRC.
The billions of cells in your body share the same DNA sequence and yet display a vast array of morphologies and functions. Understanding how this same genetic material is interpreted in diverse cell types remains a challenge. Epigenetic modifications are those that change how DNA is expressed without altering the genome sequence. For example, chemical modification of histones, the proteins that bind DNA into the large chromosome structures, can influence how genes are expressed.
In a related process, DNA itself can become methylated, which is typically thought to be a gene-silencing signal. Understanding how epigenetic modification influences gene expression has significant therapeutic potential and may provide us with insights into how we can disrupt abnormal cell divisions in cancer or promote self-renewal in stem cells for clinical use in repairing damaged or diseased tissue.
Dr. Cydney Nielsen aims to characterize epigenetic changes of stem cells, from which all other cells in the body arise. Stem cells can either self-renew to form identical daughter cells or can divide and differentiate into specialized cell types. Dr. Nielsen will use next-generation sequencing technologies and develop new data analysis techniques to examine the epigenetic changes and determine gene expression patterns in stem cells before and after differentiation.
Using these data sets, she will determine if characteristic epigenetic modification patterns exist for self-renewing cells. She will also use this information to determine if certain therapeutics are able to induce self-renewal in stem cells, to determine what the epigenetic changes are in this case, and if this ''reprogramming'' of cellular state opens up promising therapeutic applications. Such an approach will be valuable in evaluating the extent to which chemically induced cells have been reprogrammed and are appropriate for therapeutic use for regenerative medicine.
One in every eight Canadian men will be diagnosed with prostate cancer in their lifetime. Androgens, which are male sex hormones, are the primary driving force behind the development of prostate cancer and are synthesized in the testes, prostate, and in the prostate cancer tumour itself. Although once the standard of care, orchiectomy is rarely performed; continuous androgen deprivation is necessary when the cancer is very advanced. In these cases, the cancer becomes more aggressive and progresses to a stage called castration-resistant prostate cancer, which does not respond to hormonal agents. Dutasteride and abiraterone acetate are two current treatments for prostate cancer. The actions of these therapies are complementary, targeting different androgen metabolizing enzymes. Currently, dutasteride is successfully used for benign prostate hyperplasia, which is non-cancerous enlargement of the prostate. Abiraterone acetate, which was been approved in April 2011, is a promising treatment option for advanced prostate cancer patients. Clinical studies have shown that a subset of prostate cancer patients manifested resistance to abiraterone, and this suggests that there are compensatory mechanisms at work, either by supplying androgens via alternative biosynthetic pathways and/or by altering the signaling pathways involved in prostate cancer progression. The purpose of Dr. Subrata Deb’s research is to investigate the effects of abiraterone and dutasteride on pathways of androgen biosynthesis in castration-resistant prostate cancer. Mouse models of human prostate cancer, human prostate cancer cells, and human prostate tissues will be used to determine the effect of dutasteride and abiraterone acetate, either alone or in combination, on androgen formation during castration-resistant prostate cancer or in resistance to abiraterone. The aim of this research is to find the potential reasons for treatment failure in prostate cancer and aid in the development of potential treatment strategies.
The development of effective HIV/AIDS treatment has resulted in dramatic improvements in the health of people infected with the virus. Taken regularly, highly active antiretroviral therapy (HAART) interrupts the viral life cycle, suppresses the level of HIV in a patient's bloodstream, and promotes health improvements. The recent finding that individuals undergoing effective treatment are far less likely to transmit the virus to others has spurred the development of a new strategy aimed at preventing new HIV infections. Dubbed "Seek, Test and Treat", the goal of this initiative is to increase the number of people on HIV treatment in Prince George and in Vancouver's Downtown Eastside.
Dr. M-J Milloy is specifically focusing on the expansion of HIV treatment among people of Aboriginal ancestry who use illicit drugs. In Canada, young Aboriginal people are a growing sector of the HIV/AIDS pandemic, and Aboriginal people are highly over-represented among HIV-positive drug users. Dr. Milloy’s research will look at treatment for HIV and health outcomes for Aboriginal drug users and, in light of increasing calls by Aboriginal leaders for research that focuses on health and wellness among Aboriginal people, will try to identify the characteristics of successful treatment.
Dr. Milloy's research will address a number of outstanding concerns:
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Are Aboriginal individuals who are HIV-positive and use illicit drugs being effectively treated with HAART?
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What are some of the broader factors, such as stable housing or employment, that promote effective treatment?
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What is the level of viral resistance to HIV medications among Aboriginal drug users?
Much of the data for this study will come from the AIDS Care Cohort to Evaluate access to Survival Services, an ongoing study of approximately 750 HIV-positive drug users in Vancouver. The research will be supervised by Dr. Evan Adams, Physician Advisor to the First Nations Health Council, who will ensure that the research is respectful and responsible to Aboriginal participants and communities.
The information gained could be used to improve existing systems to provide HAART as well as inform new Aboriginal-led efforts to improve health and wellness. By improving HAART delivery and expanding the number of people receiving effective care for HIV infection, it is hoped that the number of new infections will also drop.
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.
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.
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.
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.
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.
