Scaling-up a community-based diabetes prevention program: A longitudinal matrixed multiple case study to examine implementation context

One in three Canadians are affected by diabetes. Diabetes prevention programs can help people considerably lower their risk for Type 2 diabetes. Yet, research understanding how to put programs in place (implement) in community settings is low. Site-specific context is often ignored, limiting program success. This means very few Canadians have access to effective diabetes prevention programs. Small Steps for Big Changes (SSBC) is a program for individuals at risk of developing Type 2 diabetes. This effective program was successfully implemented within two community sites. The program is ready to be implemented across Canada. This project will examine the implementation of SSBC in 10 unique community sites. Each site will be a case study to discover factors that affect implementation. A matrix will organize all the cases to compare results within and between sites. This method will reveal how context impacts implementation (what works, where and why). Results will offer lessons learned on how to successfully implement diabetes prevention programs across different contexts. Ultimately, this project will increase access to an effective diabetes prevention program across Canada.

Multimodal characterization and classification of bio-signals to predict cardiac arrest

Sudden cardiac arrest (SCA), due to abrupt disruption of cardiac function, is a major health problem globally. SCA can happen to anyone at any age who may or may not have been diagnosed with heart disease. SCA has a poor survival rate of about 10 percent, with an estimated 35,000 deaths in Canada annually. With an increasing rate of cases (16 percent from 2017 to 2020), SCA remains a major public health issue in British Columbia. The most effective strategy to improve survival is to achieve rapid SCA recognition, given that for every minute without cardiopulmonary resuscitation (CPR) survival rates drop by 10 percent. Wearable devices may play a major role in decreasing SCA mortality, providing real-time cardiac information for early SCA detection. My aim is to develop a wearable SCA device with embedded sensors, and use their real-time physiological data combined with artificial intelligence algorithms, to make an accurate SCA detection system. This SCA detection system will be designed to identify SCA and alert Emergency Medical Services with the individual’s location (via GPS), enabling them to provide life-saving interventions in a timely manner.

Mitotic bookmarking by transcription factors as a mechanism of transcriptional memory

Cells that are the building blocks of the organism come in different forms and functions. Stem cells are a unique type of cells, because of their ability to change (differentiate) or maintain their state. Because of this ability to differentiate into any type of cell, stem cells are on the frontiers of regenerative medicine, which is aimed to restore damaged cells, tissues or organs. The cell division (mitosis) poses a challenge for cell identity. During mitosis, the DNA is condensed into characteristic mitotic chromosomes, the nuclear membrane, separating DNA from rest of the cell, is fragmented, and the gene expression ceases. How then cells memorized which genes were expressed, to continue their expression after mitosis? The mitotic memory has been proposed as a mechanism for the maintenance of cell identity after mitosis. One arm of this mechanism, called bookmarking, is the binding of transcription factors (proteins regulating gene expression), to mitotic DNA. This project aims to establish the molecular mechanisms of mitotic bookmarking in mouse embryonic stem cells. Using methods, such as gene editing, genomics, and imaging, I will solve how stem cells maintain their identity after countless number of cell division.

The role of Baf53b in regulating neuronal gene expression and autism behaviours across development

Autism spectrum disorder (ASD) is characterized by impairments in social communication and restricted interests. Several genes have been implicated in ASD, but a group of genes in the neuronal nBAF complex have emerged as promising candidates. The nBAF complex changes the structure of DNA to influence the way several genes are expressed in a cell. To date, no research has been conducted on the role of nBAF within neuron subtypes. I will investigate the loss of the nBAF complex specifically in parvalbumin (PV) neurons in mice. PV neurons are the most abundant type of inhibitory neuron in the brain and are frequently impaired in ASD. I hypothesize that loss of the nBAF complex will alter gene expression that is necessary for proper neuron function and resulting in ASD-like behaviours. Mice lacking the nBAF complex will undergo behavioural tests that can be used as a proxy to study ASD. Next generation sequencing will be employed to investigate alterations in gene expression. This work will be the first to test how loss of the nBAF complex specifically in PV neurons might lead to behavioural changes relevant to ASDs, providing the foundation for potential treatments.

Proteome-wide mechanisms of hyperinsulinemia and sucrose-induced, tissue-specific insulin resistance

During the development of Type 2 diabetes, the body often makes more of the blood sugar-lowering hormone insulin than normal. Recent research suggests excess insulin may cause weight gain and insensitivity to insulin. Studies from our lab showed that preventing this increase of insulin can reduce weight gain and extends lifespan in mice. Too much sugar consumption also contributes to obesity and diabetes, but how this happens is still unclear. Therefore, we aim to find out whether reducing insulin can prevent the detrimental effects of high sucrose and identify the underlying causes of obesity and diabetes. So far, our experiments with mice who were given sucrose drink in place of water, have revealed that mice given that have been genetically modified to produce less insulin are protected from higher body weight and blood sugar levels. With funding from Health Research BC, we will analyze the liver, muscle, and fat of these mice using powerful techniques that can profile thousands of genes and proteins in these tissues, rather than just a few at a time. These analyses will reveal the detailed changes in the cells in response to sucrose and insulin, which will tell us how they cause obesity and diabetes and help us develop strategies for preventing diabetes.

Exploration through movement variability: How does the presence of pain affect the movement variability-adaptation process of walking?

When we walk, our bodies take each step slightly differently. This variability is how the brain explores movements so we can adapt to changing environments (e.g. bump in the sidewalk) or new challenges (e.g. painful motion). Pain from injuries or disease can lower this natural exploration because our brain avoids painful movements, ultimately limiting our ability to adapt. My study aims to understand how pain affects this variability-adaptation process in walking. In these studies, we will use electrical stimulation to create artificial knee pain, since naturally occurring pain fluctuates and is difficult to control. By synchronizing the painful stimulation with walking motions, we can precisely control the timing and severity of pain so we can measure the variability-adaptation process in real-time. First, we will test how knee pain changes movement variability. Then, we will measure how adaptation is affected by lower variability created by the pain. To conduct these projects, we will develop new wearable technology that combines electrical stimulation and motion tracking devices to perform this work in places outside the lab. The results will inform how movement variability can affect rehabilitation of painful conditions.

A novel stem cell model for human islet development and cytoarchitecture

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.

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.