Parkinson’s disease (PD) globally affects 1 in 100 adults above 60. Exposure to environmental agents including viral infection increases vulnerability to PD. Hyperactivity of brain immune cells named microglia is also a strong determinant of PD onset and progression. Altered brain functions persist in patients during and after COVID-19. Evidence in the brains of patients who died of COVID-19 show dysfunctional microglia in brain areas affected by PD. These abnormal microglia were also observed in infected monkeys without breathing difficulty. In BC, where above 89% of total SARS-CoV-2 cases do not require hospitalization, older adults totaling 41% of the population, account for 31% of total cases. In mice, SARS-CoV-2 failed to multiply in microglia but initiated robust deleterious microglial functions, which were intensified by the exposure to PD-associated abnormal proteins. Thus, we propose that COVID-19 may precipitate PD onset or exacerbate its progression. We aim to study the impact of COVID-19 pathology on PD onset/progression and microglial implication in a mouse model expressing the human receptors of SARS-COV-2. This study will inform on COVID-19 long-term effects and may position microglia as a future therapeutic target.
Program: Trainee
Coordinating movement in a complex world: How the midbrain and oculomotor cerebellum encode visual motion originating from realistic scenes to guide locomotion.
As we move about the world, we experience optic flow – the movement of surfaces and objects resulting from self-motion. Studies of human behavior have shown that optic flow is critical for controlling posture, walking, driving, and navigating complex environments. Deficits in optic flow processing are linked to diseases including vertigo, oscillopsia, ataxias, Parkinson’s disease, and Alzheimer’s disease. Determining how and where the brain processes optic flow is therefore crucial to human health and behavior, but major gaps in knowledge remain. Typically, optic flow processing is studied by exposing subjects to simple patterns. These methods allow for tight control of experimental designs, but simple patterns lack features provided by the real world – features we use every day. How and where the brain encodes realistic visual motion to control our movement is almost entirely unknown. This severely limits our ability to treat those with optic flow deficits. This proposal aims to understand how and where the brain processes visual motion originating from realistic scenes using pigeons as a model system.
End of Award Update – August 2024
Results
The most exciting result from my project was the recognition that birds, like humans, exhibit substantial and significant eye movements during locomotion. The goal of my project was to utilize birds as a model to study optic flow processing in the midbrain and cerebellum. The fact that birds and humans share similar oculomotor traits adds to the power of avian models for human neuroscience research.
Impact
I received a job that combines research with service to my community just nine months into my Health Research BC fellowship. Thus, my project is still ongoing.
Potential Influence
Rodents are typically used as model organisms to study the human brain and brain disorders, but they do not rely on vision to the same extent as humans. Birds, on the other hand, have a well-developed visual system and, like humans, rely heavily on vision for guidance. By enhancing our understanding of avian neuroscience, my project will advance the development of avian models for human neuroscience research.
Next Steps
Components of this project are currently in preparation for publication. Alongside publication, I will continue to work on this project, in collaboration with scientists at the University of British Columbia, from my new position at Northwest Indian College in Bellingham, Washington.
Impact on Research Career
The Michael Smith Health Research BC/Parkinson Society British Columbia Research Trainee Award allowed me to continue my research in BC and ultimately secure a job serving my community. Indigenous people are currently the least represented group in STEM. In my position at Northwest Indian College, I am able to continue my research project while also training the next generation of Indigenous scientists.
Multisensory integration in aging and Alzheimer’s disease
As people age, their senses become less sharp. Healthy older adults can combine information from different senses, such as hearing and vision, to make up for this. Alzheimer’s disease attacks the areas of the brain that combine sensory information. Because of this, Alzheimer’s disease patients may lose the ability to compensate for reduced sensation. This could explain why Alzheimer’s disease patients have a much larger risk of serious falls.
For my project, I will study the brain activity involved in combining information across different senses. I will record brain activity from healthy young adults, healthy older adults, and Alzheimer’s disease patients. The participants will perform a task requiring them to quickly and accurately combine visual and auditory information. I will compare recordings from the different groups to see how aging and Alzheimer’s disease affect the brain activity.
The information I learn from my project will inform approaches to treatment and accommodation. My ultimate goal is to help people live fuller, more independent lives as long as possible.
Novel Bayesian phylogenetic methods for understanding HIV evolution within and between host
Human immunodeficiency virus (HIV) the cause of AIDS continues to affect 40 million people worldwide. To tackle the HIV pandemic, we need to develop sophisticated tools that will increase our understanding of HIV. I plan to develop new tools for understanding HIV combining phylogenetic trees and Bayesian methods. A phylogenetic tree records the ancestral relationships of viruses, like a family tree of viruses. Bayesian methods are advanced statistical techniques that achieve more accurate results over traditional methods. First, I will create better tools for making diagrams of phylogenetic trees with computer software. These diagrams will make it easier for scientists to present their findings and interpret others’ results. Second, I will develop a Bayesian method to characterize the spread of HIV while protecting individuals’ identities. This will facilitate targeted intervention to stifle HIV transmission within the community. Finally, I will compare the effectiveness of different techniques to determine the make up of the infecting virus of an individual living with HIV by looking at the characteristics of their HIV. Overall, my new methods will help complete our understanding of HIV and bring an end to the HIV pandemic.
Women and Forced Migration: Inclusively Examining Access to Care at the Axes of Chronic Health and Gender-Based Violence
Forced migration occurs when people are displaced from their homes to escape harmful situations including human rights violations, and/or environmental disasters. Currently, over 40 million women and girls have been forced to migrate worldwide. Most have been racially discriminated and over 70% have been exposed to gender-based violence (GBV) including human and sex trafficking, exploitation, and forced marriage. Health impacts of GBV include chronic health issues including hypertension, diabetes, and post-traumatic stress syndrome. Canada’s population of women forced to migrate is steadily growing. However, access to timely and appropriate health services remains uncoordinated and ineffective. Upon arrival to Canada, women are left to self-navigate exclusionary and fragmented pathways to health care while also managing the effects of forced migration. In this research, the experiences of these women will be gathered and examined toward generating recommendations for enhanced access to safe and effective health care. This project responds to national and global calls to address a significant gap in knowing how to deliver timely and safe care to women impacted by forced migration and managing the chronic health sequelae of GBV.
Exploring oncology care providers’ treatment decision making and its impacts on individuals who are highly marginalized with cancer
Due to racism, discrimination, stigma, mental illness and substance use issues, and homelessness, highly marginalized adults tend to die alone, in pain, with their needs unmet, and sometimes of preventable and treatable cancers. Cancer is the leading cause of death for highly marginalized adults. Oncology care providers play a critical role in providing culturally safe, effective care that aligns with individuals’ needs, but, issues such as unstable housing, transportation barriers, mental health and substance use issues can create conditions where oncology care providers are placed in a position of making treatment decisions that are challenging because, if highly marginalized adults do come to the cancer clinic, their treatments often dictate a regimen that is difficult to follow. This study will explore the factors that oncology care providers consider when making decisions about cancer care treatments for highly marginalized adults. Results will inform the development of clinical practice guidelines to support oncology care providers’ decision-making when making treatment decisions for adults who are highly marginalized.
Strengthening safety nets to improve access to substance use and mental health services to optimize youth-determined health and wellness
Despite an increasing trend in the number of youth with substance use disorders in BC, current data shows that voluntary, community-based, and youth-friendly support services are lacking. My project aims to address this gap by learning from youth who have had their lives impacted by substance use. By engaging with youth as co-researchers in this project, I will better understand their diverse hopes, wishes and ideas for accessible, non-judgmental, and culturally centered substance use and mental health services.
First, I will establish a leadership circle that engages a diverse group of Indigenous, non-Indigenous, immigrant and refugee, 2SLGBTQIA+, and pregnant/parenting youth, who receive(d) services from our local partners, the Foundry Victoria Youth Clinic Society (VYCS) and Surrounded by Cedars Child and Family Services. We will co-create a shared vision for meaningful and accessible substance use and mental health services, grounded in each person’s own experience and recommendations. This vision will be translated into an intervention to pilot, implement, and evaluate at Foundry VYCS and inform later implementation with the Foundry Network in British Columbia.
An investigation of the healthcare and psychosocial experiences of racialized youth living with serious and life threatening illnesses
We live in a diverse Canadian society that is quickly growing in social and cultural representation. A national survey conducted in Canada in 2016 estimated that children with at least one parent that was born outside of Canada is expected to make up almost half of the total population of children in Canada by 2036. With growing diversity, it is important for us to gain a full understanding of how children’s social and cultural background can influence their health care experiences and identify any disadvantages or barriers some may face in their care are because of their backgrounds. The goal of this project is to better understand the health care experiences of racialized children and adolescents living with serious and life threatening illness, and to explore social and cultural reasons that may influence their understanding of and engagement in their care and well-being. This information will allow us to plan future care so that they best support the needs of youth with mental health and physical health concerns from all social and cultural backgrounds.
An exercise- and education-based secondary prevention program after stroke: a randomized controlled trial
30% of stroke survivors will have another stroke. To prevent this, we can try to change several factors. These factors include high blood pressure (the most important factor), high blood sugar and fat levels, poor diet and mood, and smoking. Exercise can lower blood pressure, blood sugar and fat levels and improve one’s mood. Lifestyle-management education can improve one’s diet and mood and help stop smoking. However, we do not know if exercise and education programs can lower blood pressure and prevent another stroke in stroke survivors after rehabilitation. This study will test if an exercise and education program will lower blood pressure in stroke survivors compared to education alone. Stroke survivors recently finishing rehabilitation will be assigned by chance to one of two groups. The first group will complete an 8-week exercise and education program. The second group will only complete the education program. We anticipate that stroke survivors will have lower blood pressure after completing the exercise and education program compared to education alone. This will be one of the first studies in British Columbia to test if formal exercise and education programs after rehabilitation will help prevent another stroke.
Development of a patient-centred decision aid for rehabilitation in the advanced cancer setting
Advanced cancer and its treatment can lead to physical function declines and disability. Physical function is the ability to perform activities of daily living and patients with advanced cancer describe that addressing losses in physical function is a top care priority. Cancer rehabilitation is designed to improve physical function, yet available services are underutilized by patients with advanced cancer. Poor patient and healthcare provider (HCP) communication and ineffective shared decision making about rehabilitation are key reasons for this care gap. Decision aids (DAs) are tools that enhance shared decision making, so patients know the decision to be made, understand options and outcomes, and have clarity on their personal values. Currently, a DA for cancer rehabilitation does not exist. The proposed research will develop a DA for cancer rehabilitation by determining patient decision support needs, designing a DA prototype, and evaluating the DA’s usability. The DA is a simple and low-cost tool that may improve patient and HCP communication about cancer rehabilitation, so that the top care priorities of patients with advanced cancer are better addressed within the current healthcare system.