Cancer is caused by mutations in the DNA that cause a patient’s cells to grow out of control. Some of these cancer-causing mutations change how genes are regulated; that is, which genes are turned on or off in the cell. Essentially all cancers have activated the TERT gene because TERT is essential for cancer growth. We understand TERT regulation better than most genes, but even here we cannot predict how mutations alter TERT expression. Overall, we do not understand which genes or mutations can promote cancer via altered gene regulation. Our work aims to learn the code that cancer cells use to interpret regulatory mutations. We will make many artificial mutations in large scale, and measure how much each mutation affects the amount of gene made. We will model how the cells interpret these mutations using a computer, and apply the model to find new cancer mutations. We will these computer models to discover how often mutations alter gene regulation in cancer, and highlight genes whose regulation is important in particular cancers. In the long-term, our work will allow us to better diagnose and treat cancer by showing how a particular patient’s tumor’s mutations alter gene regulation and cancer growth.
Program: Scholar
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.
Towards a mathematical theory of development
New technologies like single-cell RNA sequencing can observe biological processes at unprecedented resolution. One of the most exciting prospects associated with this new trove of data is the possibility of studying temporal processes, such as differentiation and development. How are cell types stabilized? How do they destabilize in diseases like cancer and with age? However, it is not currently possible to record dynamic changes in gene expression, because current measurement technologies are destructive. A number of recent efforts have tackled this by collecting snap-shots of single cell expression profiles along a time-course and then computationally inferring trajectories from the static snap-shots. We argue that this inference problem is easier with more data, and the right way to measure the “size” of a data set is really the number of time-points, not the number of cells. We propose to collect the first single cell RNA-seq time-course with more than one thousand distinct temporal snapshots, and we develop a novel mathematical and conceptual framework to analyze the data. This tremendous temporal resolution will give us unprecedented statistical power to discover the genetic forces controlling development.
Genomic mechanisms underlying the prenatal and early childhood origins of mental illness in children
The last decade has seen an explosion of genomic and health-related data. These data can advance precision medicine, but only if we apply the right analyses. I use statistical methods that link together many different types of large genomic and health datasets. My research identifies genomic mechanisms that lead to disease, which is the first step towards improving patient care. A primary goal of my research is to learn about the genes that cause mental illnesses like attention-deficit / hyperactivity disorder (ADHD) in children. We know that genes are important to ADHD risk. We also know that babies born small are at increased risk of ADHD, and that the placenta influences a baby’s growth in the womb. What we do not know, however, is how genes that are important to placenta function also affect a baby’s future risk of ADHD. Answers to this question will help us understand ADHD biology so that we can develop better prevention and treatment strategies and give all children the best start in life.
Towards transformative pandemic response, recovery, and preparedness: An intersectional gender analysis of the secondary effects of COVID-19 on women and healthcare providers
The response to COVID-19 has exacerbated gender inequity and gender inequities have limited the effectiveness of the COVID-19 response. This vicious cycle has been entrenched in past pandemics and will recur with future outbreaks, unless it is interrupted by intentionally transformative pandemic preparedness, response and recovery. This requires interdisciplinary research to better understand and respond to COVID-19’s secondary effects — defined as those caused by non-medical interventions to prevent primary effects (infection, morbidity and mortality). Secondary effects have long term health equity implications, with women and healthcare providers disproportionately affected. This research program aims to: 1) advance evidence of secondary effects among women and healthcare providers and 2) determine whether, how and to what effect public health policy has responded to these secondary effects. Three core projects and two collaborating projects will document the lived experiences of women and healthcare providers, while linking municipal, regional, provincial, and national level analysis to inform and promote equity-based pandemic response, recovery, and preparedness in BC and beyond.
Generating, co-creating, and implementing solutions and supports for older adults with cancer and their caregivers
The number of adults over age 65 in Canada is growing as baby boomers age. Older adults are the most likely to be diagnosed with cancer and likely to have other chronic health conditions. These health conditions may mean increased medications, medical appointments, and/or difficulties getting around, which combine to make the cancer experience more challenging. Older adults may also require help from family or friends to attend their many cancer and other health appointments (family doctor, geriatrics, and other specialists). COVID-19 has created additional challenges for older adults with reports of reduced or limited treatment offerings, and a sudden shift to virtual appointments.
My research responds to ongoing calls to rethink how we provide care for older adults with cancer. Specifically, we will partner with patients, community groups, health system leaders, and clinicians to co-create and implement tools to make cancer management easier for older adults. This work focuses on improving the processes rather than merely supporting individuals to navigate complex systems. This research will have important implications for health systems, clinicians, and researchers, but most significantly for older adults with cancer.
Evaluating systems-level interventions to reduce overdose during dual public health emergencies
Over the past two years, the COVID-19 pandemic has exacerbated the ongoing overdose public health emergency in British Columbia (BC). Over 3,700 persons have died from illicit drug-related overdose since April 2020. In the context of the sixth year of the ongoing overdose provincial public health emergency and unprecedented COVID-19 pandemic, there is urgent need to evaluate how changes to the correctional health system and prescribed safer supply interventions have effected overdose. The overarching objective of my research program is to conduct timely and policy-relevant research on overdose that informs response activities throughout the province. This will be achieved by using novel linked health data to identify trends in overdose since the original public health emergency declaration. I will also evaluate provincial interventions introduced to reduce overdose such as prescribed safer supply and systems-level changes to the delivery of health care in correctional settings. This project will directly inform provincial and regional overdose response activities through collaborations with persons with lived experience and knowledge users from the BC Overdose Emergency Response Centre.
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.
Single cell methods for characterizing genomic alterations in cancer
Cancer arises when a single cell acquires genetic alterations leading to uncontrolled replication. As tumour cells divide they continue to acquire genetic mutations which they pass on to their descendants, forming distinct subpopulations with different characteristics. The ability of tumours to generate genetic diversity and evolve in response to selective pressures can enable them to develop resistance to treatment. Certain forms of genetic alteration have been associated with poor patient survival in high grade serous ovarian cancer. Understanding the frequency with which these alterations arise within tumours and the diversity they generate requires profiling the genetic material of individual cancer cells. We will optimize experimental approaches for sequencing single tumour cells and develop computational and statistical methods to characterize this genetic diversity. This will provide researchers with new tools with which to study the mechanisms that underlie treatment resistance and patient relapse, and open the door for the development of new prognostic measures and therapeutic approaches.
Indigenous community-based health research in British Columbia’s interior
Indigenous health injustices and inequities are formed by colonial structures that are paralleled within health research itself. Therefore, Indigenous health research must re-center Indigenous Peoples approaches, or it risks re-colonization.
Thus, I aim to reframe Indigenous Peoples, cultures, knowledges, and capacities as central to a promising health future. My program of research focuses on three primary community-based health projects, which are guided by Indigenous approaches to health and research with community-partnerships as the foundation. First, in partnership with the Okanagan Nation Alliance, we are working together to frame community data within Sylix Okanagan approaches to health and data. The second project partners with Indigenous Programs and Services at the UBCO campus, to offer a healthy masculinities program for students. The third project brings together a cluster of experts to support urban Indigenous health in collaboration with Metis Centres and Friendship Centers in the Okanagan region.
My research program seeks to promote Indigenous health, health knowledges, capacities, and outcomes in ways that community understand as meaningful, and thereby support Indigenous control of Indigenous health.