Multiple sclerosis (MS) is the most common cause of neurological disability in young adults, other than trauma, with over two million people affected worldwide. Approximately 100,000 Canadians have MS, a rate that is nine times higher than the global average. MS symptoms vary widely and may affect vision, hearing, cognition, balance, and movement; negatively affecting many aspects of quality of life. To date, there is no cure or prevention for MS. Although treatments to effectively manage the clinical symptoms of MS are available, they come with several serious and even life-threatening adverse effects; and over time, MS enters a progressive phase which no known therapies can prevent or treat. MS was originally considered an autoimmune disease triggered by exposure to environmental factors, but family studies (twins, adoptees, half siblings) have clearly demonstrated an important genetic component to the disease.
The goal of this research program is to define the genetic components contributing to the onset of MS to provide new tools for scientific investigation and the development of novel and more effective treatments. To this end, Dr. Vilarino-Guell will apply new gene sequencing technologies to over 100 families with several blood relatives presenting with MS, as well as thousands of unrelated individuals diagnosed with MS. Within the last year he has identified disease-causing genetic changes for some of these families, as well as biologically-relevant genetic changes which impact disease progression and the severity of clinical symptoms. These genes and mutations have highlighted specific biological pathways implicated in the onset of progressive MS.
This research will further characterize the genes involved in these cellular processes to better understand the biological mechanisms of progressive disease. The results of Dr. Vilarino-Guell's research will provide the knowledge and tools for the therapeutic advances in the prevention and treatment of MS, tackling its highly debilitating progressive phase which is currently untreatable.
Individuals vary widely in the aspects of the world they perceive and remember: some filter their environments through rose coloured glasses to perceive sources of pleasure, while others are attuned to signs of threat. Such affective biases in attention influence memory and characterize mood disorders and pathological responses to trauma as well as addictive behaviours. Yet much remains to be learned about neural mechanisms underlying such biases, and the factors that influence their development and potential for change.
Dr. Todd's research will investigate the influence of genetic variation and life experience on emotional biases in learning, attention and memory, and how they can be harnessed to treat affective disorders and addiction. This research will have a direct impact on our understanding of basic neural mechanisms underlying such affective biases, and increase our understanding of how genetic variation and life experience shape these mechanisms to produce behaviours linked to mood disorders and addiction, with important implications for assessing vulnerability and optimizing treatment.
Dr. Todd's five-year research program will work towards an understanding of the role of common genetic variations that influence neurochemical activity in the brain, and the development of behaviour patterns that are linked to mood disorders. Extending her previous work on the influence of genetics and trauma on emotional biases in attention, she will focus on understanding neural mechanisms underlying such biases; investigate whether such biases arise out of individual differences in patterns of emotional learning; and examine the influence of a common genetic variation that influences the availability of norepinephrine in emotional learning. The results of this research will aid understanding of the currently understudied role of norepinephrine in emotional learning patterns linked to mood disorders and addiction.
In British Columbia (BC), it is estimated that 78,000 people are living with hepatitis C virus (HCV), most of whom do not even know they have the disease. If left untreated, HCV can cause serious harm, including liver cancer and death. People who inject drugs (PWID) are at elevated risk of HCV infection given their exposure to various individual and environmental circumstances, such as their ongoing addiction and barriers to accessing health care. A growing body of research suggests that harm reduction and addiction treatment programs may present important opportunities to engage PWID in the HCV treatment and care. Efforts are now underway in BC to dramatically expand access to low-threshold addiction treatment that extends beyond traditional methods. Research in this area is particularly timely, as these new policies offer an opportunity to evaluate the impacts of the expansion and optimization of addiction treatment on HCV-related outcomes among PWID.
Dr. Ti's research is an extension of past work that focused on the relationships between infectious diseases, addiction, and the delivery of harm reduction and health services. Utilizing her expertise in this area, Ti will evaluate novel interventions to reduce the health burden caused by HCV and addiction by:
- Characterizing HCV re-infection rates among PWID and examining harm reduction-based and addiction treatment interventions that may protect against reinfection.
- Evaluating evolving addiction treatment guidelines and their impact on HCV incidence among PWID.
- Evaluating the impact of innovative HCV and addiction treatment interventions on treatment uptake and completion.
This research is designed to provide evidence for health system leaders and policy makers to develop policies that are in line with evolving trends in HCV and addiction, and to support health system improvement.
Worldwide, prematurity is the leading cause of death for all infants, with almost one million deaths per year. Babies born before 32 weeks face the worst odds. These babies are only 2% of births, but they account for over 1/3 of all infant deaths. For these infants, a disease called necrotizing enterocolitis (NEC) can be one of the most deadly complications of prematurity after the first week of life. NEC is an acquired condition in which intestinal tissue suddenly becomes inflamed and then begins to die off. NEC has a high mortality rate, and, even if the baby survives NEC, they are subject to considerable life-long health problems, resulting in tremendous costs to the health care system. With rising rates of prematurity, NEC poses a significant health and financial burden on Canada.
Dr. Ryan's research will employ approaches from biochemistry, microbiology, and chemistry to identify the factors produced by beneficial bacteria found in the infant microbiome that protect against NEC. This work will provide essential information for the development of novel therapeutics and preventatives for this costly disease.
Dr. Ryan will also collaborate with the Centre for Drug Research and Development to investigate molecules identified potential new drug leads, and researchers at the Child & Family Research Institute at the BC Children's Hospital to further investigate the role of the microbiome in infant health.
In Canada, metabolic diseases (e.g. cardiovascular disease, type 2 diabetes, obesity) are leading causes of death, disability, and hospitalization. Currently, more than 10 million Canadians suffer from metabolic disease, with direct and indirect costs to the economy estimated to be $20 billion each year. Approximately 40% more men than women suffer from metabolic disease. In addition, commonly prescribed drugs used to prevent and treat metabolic disease are more effective in one sex than the other (e.g. fenofibrates). Despite these known differences in metabolic disease between men and women, prevention and treatment guidelines remain largely the same for both.
The main reason doctors do not treat men and women differently is due to lack of vital information about the fundamental metabolic differences between the sexes. The next step forward in preventing and treating metabolic disease is identification of the genes and pathways that control metabolism in each sex. This will provide researchers with a pool of promising new targets that will assist in developing therapies that will be effective in men and women, and eventually help in designing sex-specific treatment guidelines.
Dr. Rideout's research will work towards discovery of these genes and pathways using fruit flies as an innovative model, integrating the unparalleled genetic toolkit available to fly researchers with cutting-edge high-throughput metabolic analysis to answer three fundamental questions: firstly, which genes and pathways are essential for metabolic control in each sex; second, how sex-specific metabolic programs are established and maintained; and lastly, how sex differences in metabolism change in distinct contexts. Dr. Rideout will focus on sex differences in the regulation of fat storage, a key aspect of metabolism.
Dr. Rideout's research outputs will be the identification of a pool of candidate genes that affect fat storage in each sex. Building on this vital starting point by translating this knowledge into pre-clinical models, and eventually humans, she will collaborate with world-leading experts in diabetes, obesity and cardiovascular disease in the Diabetes Research Group at The University of British Columbia. The innovative approach of this research program will make important strides towards developing personalized therapies for men and women, an important goal in modern medicine.
Dr. Morin's research program will develop and apply laboratory and computational genomic methodologies that use DNA sequencing and other sensitive platforms to study the drivers of tumour onset, progression and treatment resistance in solid cancers in order to understand the somatic drivers of non-Hodgkin lymphomas (NHLs). Using massively parallel (next-generation) DNA and RNA sequencing, Dr. Morin will be able to identify somatic alterations and gene expression signatures in tumour tissue and liquid biopsies (circulating tumour DNA). To properly study such large data sets, he will utilize cutting-edge bioinformatics techniques and develop novel analytical approaches and pipelines that will allow leverage of unique sample processing techniques and applications.
Moving forward, this research will investigate aggressive subtypes of NHL including patients who typically fail standard-of-care treatments. Dr. Morin will rely on features of this malignancy such as high somatic point mutation rate, a well established list of known lymphoma-related genes, and the presence of clonal immunoglobulin rearrangements to develop assays to study the genetics of specimens from NHL patients in various ways. These include deep sequencing using a novel molecular barcoding system and digital PCR-based methods. He will continue to push the limits of sequencing technology by applying deep sequencing and whole exome sequencing to circulating tumour DNA. Under this research program, he will also continue to use a variety of laboratory and computational approaches to understand the clonal structure of NHLs, especially in the context of serial samples collected over the course of disease progression and after treatment failure or relapse.
Dr. Morin's lab, along with the BC Cancer Agency, plan to pursue options to commercialize these strategies so that a broader group of users can use these techniques for research and clinical applications. Some of the research under this program will involve evaluating the performance of novel ctDNA-based methods to study tumour genetics and evaluate treatment responsiveness. This will be conducted in the context of prospective and retrospective samples from multi-centre clinical trials in Canada. This engagement with clinicians and publications describing these trials will help accelerate the adoption of such emerging technologies to the clinic.
Neurological diseases and disorders have been estimated to affect 3.6 million Canadians living in the community and over 170,000 Canadians living in long-term care facilities, including in British Columbia. However, we have limited information about the molecular mechanisms that cause many of those neurological conditions, largely because of the complexity of our nervous system. Therefore, understanding the mechanical processes that impart precise neural circuit formation using a simple model organism is critical to try to find ways to prevent neurological diseases and cure patients.
Toward this goal, Dr. Mizumoto will use nematode Caenorhabditis elegans as a model system to investigate the mechanisms that underlie neuronal circuit development. C. elegans has a short life cycle (3 days/generation) with a simple nervous system consisting of only 302 neurons, making it a great genetic model system to study the fine neural circuit formation. Most importantly, countless studies have shown that mechanisms and molecular machineries underlying the development of the nervous system are remarkably conserved between C. elegans and humans. It is likely that the knowledge obtained from our research will be directly applicable to the human nervous system and to diseases associated with nervous system defects.
Using C. elegans, Dr. Mizumoto will explore how neurons communicate with their neighboring neurons/cells to form a stereotyped neuronal pattern at the level of single synapse, which is a specialized interface between neurons or between neurons and other type of cells (such as muscle cells), to transmit electrical signals. Using a combination of C. elegans genetics, molecular biology and microscopy, this research will move towards an understanding of the fundamental principles of neural network formation.These studies will advance health-related knowledge by providing direct targets for other researchers to test in fruit fly (Drosophila) and mammalian models of neurodevelopmental disorders affected by Sema/Plexin signaling and others, and ultimately the development of therapeutic strategies for the treatment of these disorders.
End of Award Update: April 2023
Most exciting outputs
Many of the genes that we discovered from our research in specifying synapse formation are heavily associated with various neurological conditions, which suggest that our work may have potential to better understand the disease conditions affected by mutations in these genes.
Impact so far
As our work is fundamental and basic, we do not expect the impact of our work to be immediate.
Potential influence
We hope that our discoveries would lead to the development of therapeutics to treat neurological conditions in 20 years.
Next steps
We will continue to uncover the fundamental mechanisms of synapse pattern formation and specificity using C. elegans as a model organism.
The rising incidence of type 2 diabetes (T2D) puts financial stress on health care systems in British Columbia and across the world. Lifestyle interventions can improve cardiometabolic health to prevent or treat T2D, but optimal lifestyle strategies (e.g. exercise intensity, type, timing; diet composition) are not well-defined and adherence is notoriously poor.
The goals of Dr. Little's research are to optimize lifestyle interventions for improving cardiometabolic outcomes and uncover potential mechanisms underlying these health benefits. The research program aims to improve cardiometabolic health and reduce inflammation via a series of translational studies to define the optimal exercise and diet strategies and uncover cellular mechanisms underlying the benefits. To translate findings for true health impact, YMCA has partnered to implement an HIIT walking intervention in the community. In addition, a randomized controlled trial will be implemented to evaluate the effectiveness of a pharmacist-led intervention, implemented through a network of 13 BC pharmacies, to teach patients with T2D how to follow a low-carb, high-fat (LCHF) diet while also reducing their medications. This has tremendous potential to change diabetes management in BC through an innovative pharmacist-led therapeutic nutrition program using LCHF diets.
The long-term goals of this research will be to develop optimal evidence-based exercise and diet interventions that improve patient health and inform clinical practice guidelines for the prevention and treatment of T2D. Elucidation of the cellular and molecular mechanisms underlying the anti-inflammatory effects of exercise and diet approaches will also be used to define the best anti-inflammatory lifestyle interventions, and identify potential therapeutic targets for prevention and treatment of T2D.
Among women who give birth in industrialized countries maternal age, obesity, twin or triplet pregnancy, and presence of chronic diseases such as diabetes and hypertension continue to increase. For example, 34% of mothers in Canada today are overweight or obese, and approximately 20% of births are to women over 34 years. These demographic trends highlight the need for increasingly complex obstetric care with careful prenatal monitoring and timely obstetric intervention if necessary.
Dr. Lisonkova's research will quantify the risk of severe maternal morbidity by developing a score system that will accurately distinguish between high, moderate, and low risk women. This score calculator will help, for example, women in rural areas to decide about transport to higher-level obstetric care, as these women may face geographical barriers to timely transfer. Determinants of these elevated risks will be examined, as well as whether these risks increase with distance to maternity care, seasonally (for example in winter), or occur only among women in selected geographically specific areas.
The results of this research will provide information to women who are contemplating delaying childbirth, who are overweight or obese, or have chronic health problems. This information will also help health care providers in pre-pregnancy and pregnancy counselling, and health care administrators to identify maternal care needs with respect to maternal-fetal medicine specialists and intensive care units. The maternal morbidity risk score calculator can also be used to adjust for baseline risks (maternal comorbidity, etc.) when comparing hospital performance and evaluating new safety measures in maternal care.
This project will be conducted in collaboration with the Society of Obstetricians and Gynaecologists of Canada, Public Health Agency of Canada, and the Department of Family Medicine & Midwifery, University of British Columbia. The collaboration between midwifery, family physicians and obstetricians will be beneficial especially for women in rural areas, for whom accurate risk identification is crucial.
New HIV diagnoses are 71 times higher among gay, bisexual and other men who have sex with men (GBM) than other men in Canada. Since 2010, BC has adopted Treatment as Prevention (TasP) as a policy to increase HIV testing and engage more HIV-positive individuals in effective treatment to reduce transmission at a population level. However, the number of new diagnoses among GBM in BC has remained largely unchanged. Further, surveillance shows an increase of HIV diagnoses among the youngest birth cohorts of GBM. HIV pre-exposure prophylaxis (PrEP) is a new preventive tool for HIV-negative GBM, but inaccurate information, sub-optimal adherence or risk-compensation could result in a false sense of security, paradoxically leading to increased HIV transmission. In addition to HIV, infectious syphilis is now epidemic among GBM in BC.
This research program will address the HIV and sexually transmitted infection (STI) epidemics among GBM in Metro Vancouver and BC. Dr. Lachowsky will measure HIV risk behaviour over time, determine how PrEP affects bacterial STI incidence, and analyze shifting attitudes about HIV, challenges with HIV prevention and treatment, and changes in sexual negotiation and practices. Results will directly inform population-specific, age-relevant public health policy, programming, and interventions to reduce the burden of HIV for GBM, especially young GBM.
Dr. Lachowsky will employ a bidirectional, integrated knowledge translation approach, with a Community Engagement Committee and key academic, public health, and community partners. An interactive Web 2.0 hub will allow for knowledge dissemination and generation with community and service providers, and will be complemented with more traditional presentations, workshops, and publications.This single research project is part of a larger program of research examining health disparities amongst GBM in BC and Canada using interdisciplinary, community-based approaches.
