Immune cells can be very effective at killing cancer cells, but tumours have the ability to suppress the immune system. This is why some of the best cancer therapies work by turning the immune system back on. To do this, it is key to understand what controls immune responses in the tumour. In inflammation, it has been shown that neurons can control the immune system. Interestingly, there is evidence that by removing neurons, cancer growth is reduced. We have discovered that when the “heat sensing” TRPV1 neurons are removed in mice, the tumor will grow much slower. We will looked at changes in immune cells using flow cytometry, which allows us to measure over 20 different immune cell types and discovered that these mice may have lower numbers of a rare cell type called ILC2. Next we are trying to understand how neurons are affecting these cells and the tumor growth. Finally, we will design a cell culture system where neurons and mini-cancers will be grown together to see if the tumors are secreting something that changes the expression of genes by neurons. This will lead to the development of novel therapies that activate the immune system by targeting neurons and provide new information on therapeutic avenues for breast cancer.
Program: Trainee
Exploring the natural history of chronic disease self-management and health resource utilization after stroke
The ability to effectively self-manage may empower people with stroke to optimize their recovery, health and wellbeing, and in doing so reduce healthcare costs. However, little is known about how people with stroke self-manage their recovery after hospital discharge, as well as how sociodemographic factors such as biological sex, age, stroke severity, and number of comorbidities impact how stroke survivors self-manage different areas of their lives. Therefore, this one-year longitudinal study aims to explore changes in self-management abilities among people with stroke after they have been discharged from hospital. We will also observe changes in health behaviours, emotions and life roles over the course of one year. Finally, we will also explore the association between self-management abilities, health resource use and costs over time. We hope to inform the development of targeted self-management interventions that consider the optimal timing after stroke to deliver such programs, and that allocate resources effectively for people with stroke that would optimally benefit from self-management support. This research will be presented at scientific conferences and will engage a patient partner in the translation of study findings.
Impact of TSC2-deficient neural cells on microglial structure and function in an induced human pluripotent stem cell model of tuberous sclerosis complex
Tuberous sclerosis complex (TSC) is a rare genetic disease caused by mutations in the TSC2 gene. The TSC brain develops malformed tissue clusters called cortical tubers (CTs), which cause epilepsy and cognitive problems. CTs result from abnormal cell differentiation, where clusters of enlarged neural stem cells, astroglia, and hyperactive neurons form. CTs notably present markers of cell stress and inflammation, which are known to affect organelles, cell differentiation, and neuron function in CTs. CTs are surrounded by microglia, the resident immune cell of the brain, required for proper brain function and the main drivers of inflammation. Though known to be a feature of TSC brain lesions, the role of microglia in CT formation is completely unknown. Therefore, I will investigate if microglia contribute to CT formation and, study for the first time, how the interaction with TSC2 mutant cells affect microglial function. Using advanced molecular and imaging techniques, I will study if microglia affect CT formation in a co-culture model of human pluripotent stem cell-derived microglia and TSC2 mutant neural cells. Our results will finally elucidate the role of microglia in CTs, a critical advance to uncover novel treatments for TSC.
Promoting the sustainability of digital interventions for sexually transmitted and blood-borne infections in Canda: A multi-methods study
More and more people are using digital tools to get tested for STIs. But we don’t know much about how to ensure that the public health benefit of these tools last for a long time. We call this sustainability. In this project, we want to learn how to make the benefit of these tools last. Here is what we will do:
• Review existing research to find out what things people think about when they want digital STI tools to be sustainable.
• Explore the experiences of digital STI testing programs, like BC’s GetCheckedOnline (GCO) and other similar programs. GCO is a program that lets people get tested for STIs online. We will review program documents. We will also interview the people who run the program and those who work with them. We will document the processes and factors that have made their programs sustainable so far.
• Review GCO’s data to see how people use the program. This is important because some people worry that too many people using the program too often might make it hard to keep it going.
Our project will help GCO and other programs like it plan for the future. It will also help us make a plan for how to make these programs sustainable.
Investigating the influence of residential green space on cognitive decline and dementia
The global population is aging rapidly. This demographic shift towards an older population poses a major public health challenge and highlights the need to identify strategies to support healthy aging. Prior research has suggested that green space may promote cognitive health, but there are gaps in knowledge that limit the application of findings in planning and policy to optimize health benefits. In this work, we will use long-term data on aging to study the influence of residential green space exposure on cognitive decline and dementia among middle-aged and older adults. We will advance existing knowledge by studying the health impacts of specific green space types and forms of contact, as well as pathways linking green space to health outcomes. We will use these findings to develop and apply an index of green space characteristics that are supportive of healthy cognitive aging that may be used by urban planners to direct the design of greening strategies. We will communicate our research findings to scientists, policy makers, and the public. Our aim is to help guide the creation of urban planning and public health policies that improve population health. This work will help to advance initiatives to support healthy aging.
Advancing Cardiovascular Research: Developing Vascularized Heart Organoids-on-Chips Integrating Immume Cells
Organoids, miniature organ models grown from stem cells, replicate the complexity of actual organs on a scale of about one millimeter. They exhibit similar morphology and functions but lack crucial elements like vasculature and immune response. In contrast, organs-on-chips, while providing dynamic microenvironments, typically use less sophisticated biological models. By combining these technologies, we can leverage the biological accuracy of organoids with the dynamic capabilities of organs-on-chips. This synergy aims to replicate in vivo physiology, enabling a more accurate study of disease characteristics and drug responses.
The project’s centerpiece is to engineer heart organoids-on-chips, with functional vascular and immune components, to investigate hypertrophic cardiomyopathy (HCM). We will evaluate the efficacy of drugs in mitigating hypertrophic responses. In addition, the study will include perfusion of immune cells to analyze the role of inflammation in HCM progression, investigating immune cell recruitment.
This initiative coincides with the U.S. FDA’s pivot from mandatory animal testing for new drugs, marking a significant shift towards more relevant human-based models in drug development.
Cerebrovascular physiology of circulatory death in patients undergoing medical assistance in dying (MAiD)
Patients undergoing medical assistance in dying (MAiD) can qualify as organ donors. Donation commences after death, which is declared when blood pressure drops below a certain threshold. We believe that a low enough blood pressure means the brain is no longer receiving blood, which represents true death, after which donation can begin. The time it takes for blood pressure to become low enough (ischemic time) can cause damage to organs because of reduced blood flow. If it takes too long for blood pressure to reach the threshold, too much damage occurs, and organs are discarded. The threshold value of blood pressure is based on studies of critically ill patients in the intensive care unit. We are not sure if the same thresholds would apply to patients undergoing MAiD, as their underlying physiology is different. We think the threshold would be higher for patients undergoing MAiD. We will measure blood flow velocity to the brain in patients undergoing MAiD using transcranial doppler. If blood flow stops at higher blood pressure levels than currently used cutoffs, this would reduce ischemic time and reduce damage to potential donated organs. We will report our results in scientific journals and through organ donation organizations.
Addressing inter-individual variability in aging: linking lifestyle factors to the brain and behaviour
Cognitive decline is associated with a variety of neurodegenerative disorders and is increasingly prevalent in Canada’s aging population. One of the most effective means to counteract cognitive decline is to maintain or enhance cognitive reserve. Lifestyle factors have been shown to impact cognitive reserve, but this impact varies highly across individuals. Most investigations into the effects of lifestyle factors on behavior and neural function do not capture this inter-individual variability and produced mixed, difficult to reproduce findings. This research aims to reduce this variability by clustering the population into sub-types based on their susceptibility to lifestyle changes before investigating the causal relationships between lifestyle factors, behaviour and neural function. The identified causal relationships will serve as promising targets for future clinical interventions in sub-types of our aging population that can limit the effects of cognitive decline and lower the rates of neurodegenerative diseases. In addition to the classical means of knowledge translation, this research will be shared through public presentations held by the Institute of Neuroscience and Neurotechnology at Simon Fraser University.
Structure-function relationship of retinal guanylyl cyclase, a key enzyme in phototransduction
Light adaptation is the ability of visual system to adjust its performance to the ambient level of illumination. It is fundamentally vital for the normal functioning of the visual system. During the normal cycle of day and night, the illumination of the earth’s surface varies over 11 orders of magnitude. The daily cycle of sensitivity adjustment is managed by switching between rod and cone pathways of retina. These pathways involve retinal guanylyl cyclase (retGC), an enzyme encoded by the GUCY2D gene expressed in rod and cone photoreceptors. In the light-induced signal cascade, retGC restores cGMP levels in the dark in a calcium-dependent manner. Mutations in GUCY2D are associated with recessive Leber congenital amaurosis-1 (LCA1) as well as dominant and recessive forms of cone-rod dystrophy (CORD). Presently, the molecular structure of retinal GC has not been determined; thus, its mechanism, interaction with other regulators, and identity of crucial residues conferring the activity of this enzyme have been elusive. We aim to fill this gap in our knowledge by determining the molecular structure of retGC. This information will enhance our understanding of the role of retGC in photoreceptors and diseases.
Caregiver-Child Sleep and Relationships in Canadian Foster and Kinship Families
Sleep is important for health, yet little is known about sleep in foster and kinship families. In my postdoctoral fellowship, I will lead research to learn about the sleep health, how best to support sleep, and the connection between sleep and caregiver-child relationships for foster/kinship families. In Study 1, we will synthesize research on children’s sleep in foster and kinship care. In Study 2, we will interview foster and kinship caregivers of children aged 0-5 years to learn about the caregiver and child’s sleep, and how sleep influences the caregiver-child relationship. In Study 3, we will compare sleep in foster and kinship families with other families in Canada. In Study 4, foster and kinship caregivers will help us design and test a sleep resource. We are creating an advisory panel to work with us to create research that is useful and interesting to the foster/kinship community, and respectful of different cultures and family dynamics. With the advisory panel, we will share the results in journal articles, at conferences, via webinars, and through foster/kinship organizations. This research will help healthcare professionals and policymakers understand, and help support, the sleep of families in foster and kinship care.