In Canada, more than 50,000 cardiac arrest (i.e. “heart attack”) patients simultaneously suffer from brain injury due to reduced brain blood flow and oxygen delivery. Primary brain injury occurs following the initial reduction in brain blood flow following cardiac arrest, and in some cases, secondary brain injury occurs after brain blood flow is restored to normal levels. However, the physiological mechanism(s) responsible for secondary brain injury following cardiac arrest remain unclear, and the data available in humans are very limited. We hypothesize that a key contributor to secondary brain injury following cardiac arrest is due to consequential activation of the human body’s innate immune system, which signals for excess brain inflammation and results in cellular damage. The proposed investigation, which will be conducted at Vancouver General Hospital, aims to measure key biological markers to quantify brain inflammation in post cardiac arrest patients. The findings from this study will improve our overall understanding of the mechanism(s) that contribute to brain injury characterized by reductions in blood flow and will potentially identify potential therapeutic targets and improve quality of life in these patients.
Program: Trainee
Unravelling the complexity of familial influences that shape children’s obesity-related behaviors over time
The transition from elementary to secondary school is a challenging time for children as many obesity-related behaviors tend to worsen in this period. My research will examine how the familial environment can support a healthy transition; specifically, how parenting practices influence children’s choices with respect to diet, physical activity and sedentary time. I will first synthesize the published literature about how mothers’ and fathers’ parenting practices relate to children’s obesity-related behaviors. To gather real-world data, I will then use a combination of interviews, surveys, and wearable tech (accelerometers) with 150 British Columbian families to assess their parenting practices and children’s obesity-related behaviors daily for 14 consecutive days during elementary school, and again in secondary school. These data will be analyzed to identify how variations in parenting practices affect children’s behaviors day-to-day before and after the school transition, and the interviews will help understand more deeply how familial factors influence children’s behaviors. Together, my findings will guide the development of parenting interventions to help children maintain healthy behaviors during adolescence.
Buddy Up for men’s mental health: Engaging men through mutual help and social connection
Approximately one in five men struggle with mental health challenges each year; however, men often experience unique barriers that prevent them from seeking help or accessing treatment. The COVID-19 pandemic has placed additional pressure on many men and efforts are urgently needed to tailor services and norm men’s mental health help-seeking. While asking for help may be viewed by some men as a sign of weakness, helping others is often perceived as a strength that aligns with masculine ideals. By emphasizing the benefits of mutual help, it may be possible to equip men with the skills and confidence to support other men’s mental health challenges, as well as their own. The aims of this research are to explore men’s mutual help for mental health challenges and develop an online intervention to promote mental health and social connection through shared activities (e.g. physical activity). We will conduct interviews with Canadian men and use the findings to inform the development of the e-intervention. Men will be recruited to test the intervention and provide feedback. Findings will provide important information about men’s mutual help for mental health challenges and opportunities to norm mental health promotion.
Examining stress mediated profibrotic response in HCM associated TNNT2 variants
The heart beats 100,000 times a day, and cardiac contractile proteins are essential to facilitate oxygen-rich blood circulation. Hypertrophic cardiomyopathy (HCM) is an inherited heart disease that promotes enlargement of the heart and fibrotic scars, leading to arrhythmias and sudden cardiac death (SCD). In Canada, all age groups are affected by HCM, especially children and youth, including elite athletes. The cardiac troponin T (TNNT2) gene variants account for 15 to 20 percent of HCM in humans. TNNT2 mutations can cause increased cardiac contractility and impaired heart relaxation, leading to structural remodelling and triggering arrhythmias and SCD. Currently, no specific medication is available to treat HCM patients. Previously, mouse or rabbit heart muscle cells were used for studying these TNNT2 mutations, which is not closely relevant to human physiology. Therefore, I aim to test TNNT2 mutants in human induced pluripotent stem cell-derived heart muscle cells (hiPSC-CMs) with different physiological and pathological stress conditions compared to normal hiPSC-CMs. Our research outcome will help us refine the profibrotic mechanism behind arrhythmias and SCD in HCM patients and timely intervention to manage patient care better.
Making room at the table: Understanding the mealtime experiences of racialized residents and their families in long-term care
Mealtimes in long-term care (LTC) homes are important for visible minority (e.g. Chinese, South Asian) residents’ well-being and keeps them connected with their families who help at mealtimes. Visiting restrictions during the COVID-19 pandemic meant that some families could not provide mealtime care which had negative effects on residents and families. There is very little research on the mealtime experience for visible minority residents and families and even less on their experiences during the pandemic, even though almost one-quarter of Canadians are from a visible minority group. It is important to understand these experiences to improve mealtimes in LTC homes. This qualitative study will answer the question: what are the mealtime experiences of visible minority residents and their families in LTC? The objectives of this study are to: 1) understand the mealtime experiences of visible minority residents and their families; 2) understand how these mealtime experiences are impacted by social, political, and economic factors; 3) identify ways to improve mealtime care for visible minority residents and families; and 4) share the research findings with stakeholders to improve mealtime care in LTC homes.
Dissecting heterogeneity in COPD: A functional imaging-guided-omics study
Chronic obstructive pulmonary disease (COPD) is a common lung condition with no known cure. Understanding lung abnormalities in COPD is critical to develop new treatments. However, lung abnormalities in COPD are ‘patchy’, and test samples (e.g. biopsies) used for laboratory studies may not be from the most diseased areas. We will use advanced lung imaging techniques (magnetic resonance imaging (MRI) and computed tomography (CT)) to identify ‘high-disease’ areas in the lungs of volunteers with COPD, and take samples from these areas using a camera inside the lungs (bronchoscopy). We will take samples before and after treatment with a common antibiotic medication (azithromycin) and test for changes in lung genes. Our approach may ultimately help develop new treatments for the 384 million people worldwide who suffer from COPD.
Defining optimal pregnancy weight gain ranges for Canadian women
Maternal weight gain is closely monitored during pregnancy because as weight gain increases, so does the risk of excess postpartum weight retention, diabetes, and high blood pressure. While lower weight gain may prevent these complications, it also increases the risk of poor fetal growth and stillbirth. Pregnancy weight gain recommendations that balance these risks are important. The goal of this project is to establish the optimal range of pregnancy weight gain for Canadian women. We will use existing medical records from approximately 560,000 women who delivered in BC between 2004 and 2018. We will obtain information on pregnancy weight gain, and link this with short- and longer-term health complications for mother and newborn, such as excess postpartum weight retention, maternal diabetes and heart disease, poor fetal growth, and stillbirth. We will use statistical models that enable us to consider all health complications at the same time, while accounting for the fact that some complications are more serious than others. Our findings could provide the basis for new public health recommendations on pregnancy weight gain, which could help to reduce overweight and obesity in Canadian mothers and their children.
Roles of the Lysine Methyl Transferase (KMT) 2d in hepatocyte identity and hepatocellular carcinoma progression
Liver cancer is the third most common cause of cancer-related deaths globally, and patients with liver cancer currently have limited treatment options, including tumor ablation and liver transplant. More than half of the liver cancer cases have mutations in regulators of genome structure, which play a crucial role in cellular differentiation and development by controlling gene expression patterns. Lysine Methyl Transferases 2d (KMT2d) is one of the most frequently mutated regulators. However, we do not fully understand how changes in the KMT2d can drive liver cancer. In this project, I will investigate the mechanism in which KMT2d influences liver development as well as induces liver cancer from normal liver cells using organs that mimic human livers. Moreover, discovering its interaction partners, such as transcription factors that function in turning on and off genes, will provide more comprehensive mechanistic insight into the roles of KMT2d in liver formation and health. This study will advance fundamental knowledge for future research on the liver’s developmental biology and provide promising alternative therapeutic avenues for liver cancer.
Evaluating the role and therapeutic value of Asparagine Endopeptidase (AEP) in prostate cancer
According to Canadian Cancer Society, one in eight men will be diagnosed with prostate cancer (PCa) in his lifetime. Most of the PCa initially respond to the treatment but eventually, some of the tumors become resistant and develop into an incurable disease. Mechanisms promoting the treatment-acquired resistance are still elusive. Our study exploring the alterations of global protein abundance unveiled an elevation of the Asparagine Endopeptidase (AEP) in the treated PCa cells, and repression of the elevation delayed cancer cell growth. AEP is a protease enzyme functioning in the cellular organelle lysosome to cleave and degrade specific substrate proteins. The role of AEP in the treatment resistance in PCa has not been investigated, we therefore propose to explore the mechanisms of AEP elevation upon the treatment and the role of AEP in cell division, cell death and cell spread under treatment stress. We also plan to develop small-molecule inhibitors targeting AEP to evaluate the co-targeting efficacy in combination with the conventional treatment approach. Our work may identify a novel mechanism promoting the treatment-acquired resistance and highlight AEP as a potential therapeutic target in PCa.
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.