Pancreatic cancer is the deadliest form of cancer, with an average life expectancy of three to six months after diagnosis. Surgical removal of the tumour is the only curative treatment, but the majority of patients have inoperable tumours. A promising treatment strategy for many cancers types is to kill blood vessels in tumours. When blood vessels are disrupted, the tumour becomes starved of nutrients and oxygen. Some success in has already been seen with two different types of drug treatment: drugs that act specifically on blood vessels, and standard anti-cancer drugs delivered at low but continuous doses. While these treatments are promising in the context of pancreatic cancer therapy, their specific effects on pancreatic tumours are unknown. Dr. Jennifer Flexman is studying the effects of both types of drug on tumour growth and blood vessels. Using a variety of imaging techniques and biological methods, she will investigate how the tumour microenvironment (e.g. blood flow, oxygen levels) is changed by antiangiogenic drug therapies. Experimental results could lead to a rational basis for selecting treatments that takes advantage of physiological changes in the tumour. Dr. Flexman hopes her research will ultimately lead to the development of novel and more effective treatments for a deadly and largely untreatable disease, with the end goal of improving the quality of life and prognosis for patients
Program: Trainee
Peripheral neurophysiological basis of sensorimotor deficits in individuals with essential tremor
Essential tremor (ET) is a neurological disorder characterized by shaking of the hands (and sometimes other parts of the body) that occurs with voluntary movement. Often mistaken for Parkinson’s disease, it is the most common tremor disorder. Approximately 75 per cent of people living with ET experience some limitation in their activities, and these limitations typically get worse with increasing age. Therapies for essential tremor focus on tremor reducing medications, but effective treatments remain limited. Consequently, new insights into disease mechanisms are needed to guide the development of more effective therapies. The origins of essential tremor are believed to involve abnormal rhythmic activity in the brain, which then travels down to the peripheral nervous system. However, the specific neural pathways that the tremor travels, as well as how ET influences the recruitment of muscles for movement, remains unclear. Also unknown is the impact of tremor on sensory receptors found within skeletal muscles, which provide the sense of position and movement of the limbs. Dr. Martin Héroux is conducting studies on British Columbians with ET to determine how their muscles and sensory receptors are affected by abnormal rhythmic activities of essential tremor. He hopes these studies will increase our knowledge of the neural mechanisms involved in the generation of essential tremor and provide a better understanding of the motor-sensory deficits associated with tremor disorders. Ultimately, this knowledge could contribute to the development of more effective anti-tremor therapies.
Modulation of ocular motor decisions by reward: an investigation of neural processes using converging methods
The prospect of reward or punishment is known to affect how people make decisions. However, it is not clear which neural systems are involved in this process. This is an important topic in healthcare, because impaired processing of reward information is known to affect the decision-making abilities of many people, including those with damage to the frontal lobe of their brains, Parkinson’s disease, depression/anxiety, obsessive compulsive disorder, and even normal aging. A striking example of this situation occurs among some people with Parkinson’s disease, who can develop pathological gambling behaviours as a result of taking dopaminergic drugs. An effective way to study these neural systems is to track eye movement decisions – in other words where people focus their visual attention. Typically, people are faster to make an eye movement and are more accurate in their eye positions when the movement is rewarded by monetary gain. However, these effects are degraded in certain psychiatric conditions, such as anxiety and depression. Dr. Linda Lanyon is investigating the brain circuits that mediate these reward-related decisions in healthy humans. Her findings will enable her to develop a computer model of the brain circuitry and function that is able to simulate the behaviours observed in humans. In addition to demonstrating how these systems operate in healthy humans, the computer model can also be selectively damaged in order to simulate pathological behaviours observed in patients. By using healthy subjects to create a computer model for decision-making, Linda hopes to improve the understanding of the pathology of neurologically-impaired circuits.
Examining the interplay between adherence and antiretroviral treatment on disease outcomes over time in HIV/AIDS-infected patients
HIV therapy has evolved tremendously due to the development of new drugs, new technologies to measure viral response and drug resistance, and an improved understanding of how the virus progresses in the body. Modern highly active antiretroviral therapies (HAART) suppress the amount of virus circulating in the blood to nearly undetectable levels for long periods, enabling the immune system to rebound, reducing HIV drug resistance and preventing this otherwise fatal disease from progressing. Clinicians have identified that many people on HAART therapies do not fully adhere to the prescribed therapy, and that their level of adherence typically changes over time. This lack of adherence is known to increase the risk of illness and death, but the specifics remain unclear. More information is needed to determine how adherence dynamically affects disease progression and outcomes, so those at higher risk of treatment failure can be identified in advance and helped with their treatment. Dr. Viviane Lima is exploring the relationship between regimen-specific adherence for key HAART therapies and the disease outcomes for patients. She will determine the levels of adherence required at each stage to reduce or prevent a number of disease outcomes: viral rebound, immune cell loss, HIV drug resistance, the emergence of AIDS-related conditions, and death. She hypothesizes that for each disease outcome, there is a distinct, clinically-significant interaction between adherence and type of HAART therapy. Long-term management of HIV/AIDS requires a long-term commitment from patients to adhere to therapy, a high level of expertise among practitioners to deal with complex and rapidly evolving treatments, and the development of clinically meaningful tools to enhance adherence over time and across varied treatments. Lima’s study will provide an evidence base to identify best treatment practices.
Genetics of healthy cardiovascular aging
Statistics Canada projects that there will be more than 1.6 million seniors over 85 by the year 2041. Only a minority who reach this age maintain a good quality of life and are free of major age-related diseases such as cardiovascular disease (CVD), cancer, lung disease, diabetes, and Alzheimer’s disease. Advancing age is the biggest risk factor for cardiovascular disease. However, a minority of people older than 85 — called “”super seniors”” — seem resistant to the most common age-related diseases, including CVD. These people may represent a group that either lacks genetic susceptibility factors that contribute to disease in the majority of people or may possess genetic resistance factors that enhance their ability to resist disease and prolong lifespan. Dr. Maziar Rahmani seeks to answer whether people whose hearts remain healthy well into their 80s and 90s have “good genes.” He is studying more than one thousand residents in the Metro Vancouver area, using cutting-edge technologies to scan the entire genome of each study participant. He will look across more than a million potential variances to find genetic commonalities among super seniors in Vancouver, and compare these findings to other studies using European and other North American populations. Identifying and understanding genetic factors that influence resistance or susceptibility to heart problems could open the way for personalized, optimized disease prevention and treatment strategies.
Statistical models for clinical genomics of cancer
Ovarian cancer is the most fatal gynecological cancer in North American women and the fifth most common cause of cancer death. Breast cancer is the most common cancer in women worldwide. Recent approaches to improving clinical outcomes for these two diseases have focused on defining distinct subtypes within ovarian and breast tumours that differ in their clinical outcomes and responses to therapy. Preliminary evidence suggests that subtypes can be detected from biopsies by performing state-of-the-art molecular tests to determine specific molecules (called markers) that distinguish the subtypes. It is also expected that an even smaller subset of markers could be used as indicators for determining prognosis and for directing therapy tailored to the subtype. A number of BC research programs are currently working collaboratively to identify and characterize the subtypes of ovarian and breast cancers, using more than 2,000 breast cancer and 400 ovarian cancer tumours for which clinical outcomes are known. This work generates massive amounts of molecular data (more than 100,000 data points per tumour). Previously supported by MSFHR funding for his PhD training, Dr. Sohrab Shah focuses his post doctoral work on developing bioinformatics (the application of computer science tools and research to biology) and statistical modeling approaches that can help pinpoint potential markers among the reams of data. Shah’s research is key to developing tools that help uncover the molecular characteristics of the subtypes of breast and ovarian cancers, and provide state-of-the-art classifiers for improved outcomes for patients with these devastating diseases.
Modulating mood with transcranial direct current stimulation: basic research and clinical applications for treating depression
Approximately 8 per cent of all Canadian adults will experience at least one major episode of depression during their lifetimes, and up to 6.5 per cent of Canadian children currently meet the criteria for clinical depression. Efforts to understand the neural mechanisms underlying depression and to develop new treatment methods for the mood disorder have the potential to facilitate improvements in quality of life for people throughout Canada and around the world. Neuroimaging studies show that negative mood and depression are associated with increased activity in the right prefrontal cortex and decreased neural activity in the left prefrontal cortex. Dr. Bradley Vines is examining how changes in neural activity in the prefrontal cortex influence mood. He is also exploring the therapeutic potential of transcranial direct current stimulation (TDCS) as a treatment for clinical depression. TDCS is a safe, painless, and non-invasive brain stimulation technique that modulates neural activity in targeted brain areas. It has been shown to significantly influence behavioural and cognitive performance. The technique involves running a low-level direct current between two electrodes placed on a person’s scalp. The neurons underneath the positively-charged anode fire more rapidly, whereas the neurons underneath the negatively-charged cathode become less active. Using tDCS, it would be possible to simultaneously increase neural activity in the left prefrontal cortex and decrease activity in the right prefrontal cortex – potentially correcting the neural imbalance that is characteristic of depression. Vines’ research promises to advance our understanding of how the prefrontal cortex contributes to emotional states and mood disorders, and to determine the viability of using tDCS as a therapy for depression.
Defining perceptions and utilization of pharmacotherapy for menopausal symptoms among Chinese immigrant women in British Columbia
By 2017, one in five people living in Canada will belong to a visible minority group, and nearly half (between 3.2 and 4.4 million) will be Chinese or South Asian. A variety of factors – including language, education, socioeconomic status and employment – affect health and access to health care. Gender, ethnicity, and immigration are also increasingly recognized to have a significant impact. Medication use for menopausal symptoms has not been explored in the context of gender, ethnicity and immigration in Canada. Women, particularly Chinese women, have historically been underrepresented in clinical trials, resulting in a limited understanding in this group. As a result, few studies have examined Chinese immigrant women’s experiences with medications for menopausal symptoms. Dr. Elaine Chong will focus on a knowledge gap relating to medications used for menopausal symptoms, among Chinese immigrant women who access health services through a specialized outpatient clinic in Vancouver. Chinese immigrant women constitute a group that has health disparities and may have less access to evidence-based care than other women in Canada. Chong’s research will help shed light on differences in medication use and health disparities among a vulnerable group. She hopes these results can be applied to culturally-appropriate interventions that support Chinese immigrant women in attaining optimal health status.
Validating a computer adaptive test for the measurement of health outcomes in adults with musculoskeletal disorders
Although effective medical treatments and supportive services for people with joint problems (such as arthritis) are available, the choice of specific treatments and services offered must be guided by knowledge about the various challenges they encounter in their daily lives. Important health outcomes reported by people with joint problems can include their competence with daily activities, their ability to walk and handle objects, their pain or discomfort, and their emotional wellbeing. Computerized adaptive assessment systems can be used to efficiently obtain information about self-reported health outcomes by selectively administering questions that are most meaningful and relevant to an individual’s condition. The resultant information can be used to track changes in a person’s health outcomes over time and facilitate decision-making and communication between patients and health care professionals about the impact of arthritis. This can provide the patient with more information and control with respect to their choice of treatment. Dr. Richard Sawatzky is investigating whether a recently-developed computerized health outcomes assessment system for people with arthritis provides accurate and trustworthy information. He is specifically examining the extent to which the information provided by system is valid irrespective of differences among individuals that may lead to variations in how they interpret and answer the questions. His assessment uses data from almost 6,500 participants across the country. Sawatzky’s research will ensure that the individual’s experiences with respect to several health outcomes relevant to arthritis are obtained and reported in the most accurate, informative, and efficient manner.
What happens after conventional treatment? Investigating the feasibility of a complementary and alternative medicine (CAM) modality for breast cancer survivors
It is estimated that there are well over 10.5 million cancer survivors in North America and over 40 percent of the females are breast cancer survivors. Nearly three quarters of the cancer survivors experience some kind of debilitating effect(s) from cancer diagnosis and conventional treatments, including considerable fatigue, psychological distress, impaired quality of life, cognitive dysfunction, cardiac toxicity, loss of appetite, poor mental health and reduced physical and sexual functioning. These effects are particularly prevalent in breast cancer survivors who received multiple treatments over an extended period of time. Increasingly, health care providers and patients are looking to innovative solutions to address adverse effects that are often poorly managed by conventional medicine. Approximately 80 per cent of breast cancer survivors use some form of complementary and alternative medicine (CAM) to help them manage the difficult physiological, emotional and psychological symptoms that often persist. A growing body of randomized controlled research implies that yoga therapy has physiological and psychosocial benefits for the chronically ill – however, controlled trials are lacking for its use within cancer. Dr. Suzanne Slocum_Gori has previously conducted NIH studies within the US investigating yoga therapy for HIV/AIDS. Now, she’s focusing on the feasibility of using yoga therapy as part of the BC Cancer Agency’s (BCCA) health services for breast cancer survivors. Slocum-Gori’s study will consist of two phases. She will examine both the acceptability and sustainability of such a program within BCCA’s mainstream health system for Phase I, including the identification of factors that promote and impede acceptability, sustainability, recruitment and attrition. Phase II of the study will consist of a controlled pilot study to measure the effectiveness of yoga therapy for breast cancer survivors over time.