The cultivation of stem cells to insulin-producing beta cells offers an unlimited source of transplantable material for diabetes treatment. However, currently manufactured beta cells do not function precisely like the healthy ones in our bodies. Human islets are cell clusters mainly comprised of a mix of endocrine cell types, and interactions among them are critical in controlling insulin secretion. However, this point has been overlooked by current manufacturing methods that typically attempt to make clusters enriched only for beta cells. The absence of other islet cell types may therefore be a leading cause of the failure to obtain properly regulated insulin production. We recently developed a method to coax stem cells into islet clusters that are enriched for major endocrine cell types. Interestingly, these islets formed through an essential but unidentified “budding process” and self-organized into distinct cellular arrangements over time. Our goal is to elucidate the mechanisms that regulate islet formation, including the ways in which the cells assemble and impact islet function. Success could facilitate methods to manufacture islet cells with more robust insulin production and guide cell replacement strategies for diabetes.
Research Location: University of British Columbia
Pain and healthcare experiences of sex and gender minority citizens living with chronic pain in Canada
One in four people in Canada live with chronic pain. These individuals experience poorer health outcomes, higher healthcare services use, and lower quality of life. Studies show males and females experience pain differently, for example differences in pain sensitivity and pain control. But little is known about pain experiences in people who identify as a sex and gender minority, meaning a person’s sexual orientation or gender identity differs from traditional societal views. Sex and gender minority persons report higher pain and experience unique life stressors (e.g. discrimination), which may lead to worsening of their pain. We aim to study 1) pain experiences and 2) strategies to improve healthcare experiences for individuals who identify as sex and gender minority living with chronic pain by collaborating with patient and public stakeholders to answer these questions. Involving persons who identify as sex and gender minority with chronic pain in research studies is important because it provides them with a voice to offer personal stories and perspectives. Community engagement will help researchers ask the “right questions” and guide research priorities to improve the lives of people who face similar health challenges.
Sex specific characterization of microRNAs in fibroadipogenic progenitors in cancer cachexia
More than 80 percent of patients with cancer encounter a severe loss of muscle and fat leading to a devastating condition called cachexia, a condition that severely affects the quality of life. Incidence of cachexia is higher in males than in females. In general, and in cancer, men have increased muscle mass while women have higher fat mass. Understanding the inherent sex-differences in disease will aid in developing effective treatment options. During muscle injury, different types of cells in muscle act in synchrony for its repair. One type of supporting cell is called as fibroadipogenic progenitors (FAPs), which provide the required growth factors for muscle regeneration. Impairment in FAPs production or function would lead to unhealthy accumulation of fat in muscle, leading to muscle wasting. The role of molecules such as microRNAs (miRNAs) contributing to this impairment remains unknown in cachexia. miRNAs are small molecules that controls expression of several genes. The current proposal aims to understand the role of sex-specific dysregulated miRNAs in FAPs and if therapeutically targeting the defective miRNAs may ameliorate muscle wasting thereby improving survival, quality of life in patients with cachexia.
The impact of the COVID-19 pandemic on access to adequate care for serious mental disorders in British Columbia
The Covid-19 pandemic has created new challenges for the treatment of serious mental disorders such as schizophrenia and bipolar disorder. Patient avoidance of health services and the rapid switch from in-person to virtual delivery of services may have created barriers to accessing specialist services. The aim of the current study is to evaluate whether access to adequate psychiatric care for serious mental disorders changed between 2015 and 2022, and particularly after the onset of the pandemic. In addition, we will examine whether any disparities in access by demographic (age, sex, neighbourhood income quintile, geographic location) clinical (diagnosis and presence of substance use disorder) and health system factors have increased or decreased over this time period. Findings from this study will have important implications for the provision of mental health services for serious mental disorders in British Columbia.
Immunomodulatory effects of endogenous retroviruses in infection and inflammation
Infectious diseases and chronic inflammatory diseases plague human health and account for roughly 60 percent of deaths worldwide. Basic and translational research that reveal new mechanisms of immune modulation during viral infection and chronic inflammatory diseases are therefore critical to lower health burden. Genetic and environmental factors influence immune responses, but we are far from achieving a comprehensive understanding of mechanisms that underlie protective responses and unwanted excessive inflammation. Endogenous retroviruses (ERVs) are viral sequences that are major components of all human genomes, yet ERVs have been largely overlooked in the context of infectious diseases and chronic inflammation. Dr. Maria Tokuyama will develop a highly innovative and rigorous research program to identify novel interactions between ERVs and the immune system and determine interactions that boost antiviral responses in the context of viral infection and those that promote excessive inflammation in the context of chronic inflammatory diseases. This research will expand our knowledge of the underlying mechanisms of disease and will lead to health and economic benefits for Canadians.
Optimal pregnancy and postpartum health for everyone
After childbirth, mothers are at risk of death and disease. Patient engagement can improve the relevance and impact of research in this area; however, patient partners often do not reflect the diversity of the community. This limits the research and its results. This is especially important in BC, which is the most ethnically diverse province in Canada. The proposed research project aims to answer the following three questions: 1) How can we improve the diversity of patient partners in pregnancy and postpartum-related research? 2) Is a mobile application appropriate and acceptable for self-screening of postpartum complications? 3) What is the frequency, timing, and factors associated with postpartum complications and hospital readmissions in BC? The proposed research will promote equitable representation of pregnant and postpartum individuals in research, improving our understanding of their health and health concerns. It will be a core component of my portfolio of patient-oriented maternal health research in BC and globally.
Using high-throughput experiments and machine learning to understand the role of non-coding mutations in cancer
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.
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.
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.
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.