Type 1 Long QT syndrome (LQT1) and Short QT syndrome (SQT) result in life-threatening irregular heartbeats that can cause sudden death. LQT1 affects around 1 in 2,500 adults, whereas SQT may impact twice as many individuals, with high prevalence of congenital LQT in a First Nations community in Northern BC. Current treatments are inefficient and therefore, new therapeutic strategies are needed. Abnormalities of the protein, KCNQ1, result in these diseases. Normal KCNQ1 function moves charged ions through heart membranes. We generally know how KCNQ1 functions in health and disease; however, the exact mechanisms are not yet fully understood. We need to study the 3D structural changes that happen to KCNQ1 in the presence of certain compounds to understand how KCNQ1 functions. I will study the 3D structures of such complexes by using cryo-electron microscopy, a technique to study structural biology, and functional characterization. The new knowledge that will be produced will help better understand how such proteins cause disease and lead to new therapeutics for better human health.
Research Location: University of British Columbia - Vancouver Campus
Transforming prisons and improving health outcomes for people who use drugs: An evaluation of BC’s prison-based therapeutic community
People with substance use disorders (SUD) are more likely than those without SUD to be sent to prison and to experience negative outcomes after release. Prisons are not typically ideal environments to treat complex health issues including SUD. Therapeutic communities (TCs) offer an alternative to traditional forms of punishment, providing the environment for belonging and relationship-building, through activities such as group-based therapy, education/work, and community participation. The proposed study will evaluate Guthrie House, BC’s first and only prison-based TC which opened in 2007 at Nanaimo Correctional Centre. The study aims to identify the TC-related mechanisms of change associated with health and criminal justice outcomes, and will involve three main components: a survey with TC clients, interviews with TC and correctional staff, and linked administrative data analyses. This study has the potential to identify promising approaches to supporting people with SUD who experience incarceration. This work will add meaningfully to the policy initiatives in BC focused on reducing overdose and increasing access to SUD care.
Post-transcriptional regulation of hematopoietic stem cell function during normal and malignant hematopoiesis
In 2016, there were approximately 22,510 Canadians living with leukemia and an estimated 2,900 Canadians died from leukemia. Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults. About 30 percent of AML patients eventually relapse after treatment and suffer from very poor overall survival at this stage. It is postulated that leukemia stem cells (LSCs), a small population of leukemia cells characterized with regenerative ability, mediate resistance and relapse after therapy. My work sought to uncover the largely unknown role of the processes that control protein generation in maintaining blood stem cells and how it contributes to transformation of leukemia stem cells in cancer. This research program aims to identify new factors, which can serve as targetable molecules and pathways to specifically eliminate leukemia cells while sparing normal cells. The work will provide the scientific foundation for future developments of therapy targeting these pathways as a novel strategy in eradicating leukemia stem cells to improve outcomes in AML patients.
Light and drug delivery coupled with biomaterials to improve motor function after spinal cord injury in animal models
Spinal cord injury (SCI) is a debilitating condition with no available cure directly affecting ~80,000 Canadians. The major challenges to overcome include: i) the limited spontaneous regeneration of nerve fibers (axons) after the injury; ii) scar tissue formation at the injury site (lesion), which inhibits the growth of axons; and iii) the difficulty in guiding axons to grow across the lesion. The present work proposes a novel solution that combines optical stimulation technology and biomaterials to promote axonal growth, inhibit the formation of scar tissue using targeted drug delivery, and guide growing axons across the lesion. My team has developed fully implantable multifunctional neural probes for the delivery of both light and drugs to the spinal cord injury site as well as biomaterials to guide the growth to axons across the lesion. The MSFHR Scholar Program would support our work to integrate these strategies and create a therapy that helps us understand the combined effects of light stimulation, drug delivery, and axon guidance on motor function recovery after SCI in animal models. The outcomes will support treatment development for SCI based on a better mechanistic understanding of regeneration.
Development of an ex-vivo-in-silico framework to inform medication use decisions for breastfeeding women
Children can inadvertently be exposed to the medications their mothers receive through breastmilk. As such, breastfeeding mothers need to weigh both the risks and benefits of medication use for themselves as well as their children. Unfortunately, the majority of drugs prescribed to breastfeeding women lack sufficient information to understand these risks. Due to this lack of information, women may opt to delay needed drug therapy or discontinue breastfeeding altogether — choices that can negatively impact the health of both mother and child. The proposed research program looks to address this information gap by combining lab-based studies with advanced computer modelling to predict how drug intake by the mother translates to drug exposure in the breastfed child. Lab-based studies will answer the question, “How much drug is present in breastmilk?” Whereas, advanced computing will be used to create virtual children and mothers to answer the question, “How much of the drug administered to the mother will be transferred to the breastfeeding child?” This will work ultimately serve to provide breastfeeding women and their caregivers with vital information to make the decisions regarding safe and effective drug therapy.
Kitchen table justice: Co-developing Indigenous-informed food justice participatory action research strategy to support holistic health and redress health inequities with paroled women in BC
This grant will support research planning with women who have been recently incarcerated and will directly support future research guided by Indigenous approaches to holistic health and health equity through food-based program development. We will build relationships with paroled research users through the making and sharing of food, and the inclusion of research users, stakeholders and Indigenous Elders in all activities. Specifically, we will: (i) conduct a literature synthesis on the potentials of food justice to support holistic health equity for women on parole, and (ii) meet bi-weekly to: (a) collaboratively develop a terms of reference and governance structure that outlines team roles and responsibilities and decision-making processes; (b) engage in co-learning about food-related health and social inequities to develop a shared understanding of the potentials of food to support health; and (c) explore potential solutions and actions to redress overlapping health, prison and food inequities. Additionally, we will: (d) collaboratively plan and develop a grant application to support subsequent research to co-develop a food justice health intervention with and for women leaving prison in BC.
Team members: Angel Willard (Elizabeth Fry Society of Greater Vancouver); Kelsey Timler (UBC); Lisa Bowden (Elizabeth Fry Society of Greater Vancouver); Nyki Kish-Field (University of Fraser Valley); Lyana Patrick (Simon Fraser University); Valerie Napoleon (University of Victoria)
Cancer and aging research engagement: Identifying priorities to enhance research and care of older adults with cancer and their caregivers
Cancer is most common amongst older adults. Older adults with cancer have distinct needs due to underlying health conditions and social situations, which may include a lack of social and financial supports. These factors often affect their ability to manage treatments, cope with treatment side effects, and make health care decisions. For older adults who do not speak English, have limited knowledge about the health care system, or have poor understanding of health or illness; navigating the cancer system is even harder. Older adults are often cared for by informal caregivers, such as family members, due to limited resources or services available to support older adults with cancer in the community. Caregivers face challenges trying to balance their caregiver role, not only for the older adult, but also for their younger dependents; work; and their own health needs.
Through virtual meetings and priority setting work, we will achieve the following goals: establish partnerships between older adults, caregivers, and diverse seniors’ groups; identify key research priorities to improve cancer care for older adults and their caregivers in BC; and develop a five-year research agenda to improve care for older adults with cancer.
Team members: Caroline Mariano (BC Cancer); Bonnie Leung (BC Cancer); Lorelei Newton (University of Victoria, and Canadian Association of Nurses in Oncology); Daniel Renouf (BC Cancer); Sabrina Wong (UBC); Lisa Quay (Jewish Community Centre); Keiko Funahashi (Tonari Gumi); Anthony Kuperschmidt (West End Seniors Network)
How can health economic models better reflect patient and public values? Understanding stakeholder perspectives and research priorities through the Peer Models Network
Researchers build computer models to explore the potential costs and benefits of different ways of providing health care — and model results influence health services in BC. This project will bring together BC experts (‘health economic modelers’) and connect them with research users and members of patient and public organizations. First, modelers will meet with research users to understand current processes of model development, decision-making, patient and public involvement, and transparency (i.e. clear, culturally safe, accessible information) in modeling. Then, modelers, research users, and members of patient and public organizations will meet at two online engagement sessions. Sessions will highlight what health economic modeling is; how models are developed; why modeling involves making social and ethical decisions that affect patients and members of the public; what modeling processes in BC are like; how models are being used in policy-making; where patient and public input in modeling is most important; and the goals of transparency. Participants will be invited to discuss and record their research priorities and perspectives on appropriate processes, creating shareable knowledge and connections for future collaboration.
Team members: Ian Cromwell (Canadian Agency for Drugs and Technology in Health); Stephanie Harvard (UBC); Manik Saini (BC Ministry of Health); Jemal Mohamed (BC Ministry of Health); Leah Grantham (Independent Consultant); Amin Adibi (UBC); Eric Winsberg (University of South Florida); Nick Bansback (UBC); David Whitehurst (Simon Fraser University)
Walking away from depression: Leveraging physical activity to treat symptoms and improve well-being in individuals with major depressive disorder
Major depressive disorder (“MDD”) is a chronic condition characterized by sadness and loss of pleasure. MDD is a leading cause of disability (WHO, 2020), and costs the Canadian economy billions each year (CAMH, 2021; CASHC, 2016). In 2016, the Canadian Network for Mood and Anxiety Treatment recognized exercise as a first-line treatment for MDD. This statement should have revolutionized care: not only does exercise reduce symptoms, but it also improves health and quality of life. However, the past five years have seen little progress in “mainstreaming” exercise as a treatment option. This means patients are being denied access to a safe and effective treatment.
We are left with a question: How can we get more people with MDD more active more often?
The purpose of my postdoctoral fellowship is to answer this question. I will oversee a program of research that examines how British Columbia’s public health system can provide exercise as a treatment for MDD. I will investigate barriers to uptake; strategies to overcome barriers; and engage in program development and evaluation. This research will be conducted in collaboration with patients, healthcare providers, and communities to ensure it is feasible, relevant, and sustainable.
Psychiatric morbidity in multiple sclerosis during the prodromal period (Psych-MS)
Multiple sclerosis (MS) likely begins years before the first neurological symptom by a set of not-clearly defined, subtle symptoms, leading patients to increasingly seek medical attention years before diagnosis. Some may even require psychiatric care during this period. This phase of the disease is known as the MS prodrome. Our plan is to better characterize psychiatric healthcare encounters during this phase of the disease by analyzing anonymized and linked administrative health data that is generated whenever an individual visits a doctor, is admitted to a hospital, or fills a prescription at a pharmacy. We aim to specifically look at any visits resulting in a diagnosis of depression, anxiety, or bipolar disorder by a physician, any visits to psychiatrists, and also look at prescriptions filled for medications, such as antidepressants. These ‘psychiatric data’ generated during the five years before patients’ first MS symptom will be explored and compared to that of individuals from the general population. We believe that advancing our understanding of the MS prodrome may help us identify patients sooner in their disease course, allowing for earlier treatment, and eventually prevent disease progression.