xacqanaǂ itkiniǂ (Many Ways of Working on the Same Thing) is a long-term working relationship between Ktunaxa First Nation, Interior Health, University of Victoria, and University of British Columbia – Okanagan. Over the last three years, the xacqanal itkinil team developed a new approach to research that is led by Ktunaxa peoples and reflects Ktunaxa culture. We tested this approach in Ktunaxa communities by hosting a series of gatherings and land-based activities, where community members shared their vision for a healthy community. The team recently received a five-year CIHR Project Grant to build off the first phase of the partnership to work towards Ktunaxa Nation’s vision for a healthy community. We will work with community partners to co-design and implement interventions (i.e. programs, policies, practices), with the aim of transforming the culture of the health system to better serve Indigenous peoples and the wider population. This fellowship will directly contribute to monitoring and evaluating the interventions and their implementation to understand what is working well, what challenges are encountered along the way and how they are addressed, as well as how this work can be carried forward into the future.
Program: Trainee
Transforming prisons and improving health outcomes for people who use drugs: An evaluation of BC’s prison-based therapeutic community
People with substance use disorders (SUD) are more likely than those without SUD to be sent to prison and to experience negative outcomes after release. Prisons are not typically ideal environments to treat complex health issues including SUD. Therapeutic communities (TCs) offer an alternative to traditional forms of punishment, providing the environment for belonging and relationship-building, through activities such as group-based therapy, education/work, and community participation. The proposed study will evaluate Guthrie House, BC’s first and only prison-based TC which opened in 2007 at Nanaimo Correctional Centre. The study aims to identify the TC-related mechanisms of change associated with health and criminal justice outcomes, and will involve three main components: a survey with TC clients, interviews with TC and correctional staff, and linked administrative data analyses. This study has the potential to identify promising approaches to supporting people with SUD who experience incarceration. This work will add meaningfully to the policy initiatives in BC focused on reducing overdose and increasing access to SUD care.
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.
Regulation of anabolic metabolism in anti-tumour T cells
Our immune system protects of our body by detecting and destroying cells that are potentially cancerous. Sometimes, our immune system fails to detect a problem, leading to cancer. In pediatric cancer, CD8 T cells fail to destroy cancer cells. CD8 T cells are white blood cells specialized in the detection and attack of cancer cells. Like us, CD8 T cells need to “eat” to stay alive, to move, and to function. Without nutrients, they can’t fight off cancerous cells. In cancer, there is a fight for nutrients between CD8 T cells and cancer cells. CD8 T cells have to quickly adapt to make sure they can maintain their protective functions. We know that CD8 T cells can rapidly switch from using nutrients to grow, to burning them to make energy, but we do not know how it is regulated. The aim of my project is to study how CD8 T cells know which nutrients are around them, and how they “choose” to switch between growing and burning. Why is it important? If we grow CD8 T cells in a laboratory setting, restrict their food, and re-feed them, they provide better protection against cancer. Understanding how CD8 T cells “eat” and use nutrients to grow or burn energy to kill cancer cells will help develop better therapies to treat pediatric cancer.
Outcomes of a ketogenic dietary intervention on the gut microbiome-microglial brain axis and schizophrenia-like behaviour in mice exposed to a double-hit immune challenge
Alterations in microorganisms present in the gut are associated with various mental health disorders. It is possible that this is due to changes in microglia, the immune cells that fight infections in the brain. Microglia can consume neurons, which are the cells that talk to one another in the brain. It is possible that changes in gut microorganisms make these immune cells to eat up brain cells excessively and uncontrollably, which causes mental illness. To understand this, we will infect laboratory mice with infectious agents during pregnancy and expose them to stress during adolescence. After testing the mice for behavioral alterations, we will use imaging techniques to assess how gut microorganisms can influence microglia. We will then determine if ketogenic treatments with a clinically approved high fat and low carbohydrate diet, showing benefits on the gut and brain, can reverse harmful effects on these immune cells in the brain. Together these investigations will provide novel insights into how the gut microorganisms can affect the brain immune cells and alter behavior, resulting in mental illnesses. This research may provide new targets for the therapeutic management of mental health conditions that include schizophrenia.
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.
Linking administrative and survey data to examine substance use related diagnoses, hospitalization and mortality among gay, bisexual and other men who have sex with men in Metro Vancouver
Every day, over 400 Canadians are hospitalized because of drug and alcohol-related causes. These admissions are widespread, costly and deadly. This issue is especially problematic in British Columbia (BC) where hospitalizations related to alcohol abuse are highest in the country. Population data consistently highlight that licit and illicit substance use is more common among gay, bisexual and other men who have sex with men (GBM) compared with heterosexual individuals. However, research assessing substance use related mental and behavioral disorders, hospitalizations and mortality is lacking for GBM due to the lack of identifiers for sexual orientation in administrative research. This study links administrative and survey data to examine substance use related outcomes from 2012 to 2020 and compare these rates between GBM and heterosexual males in BC. Further, we will use cohort survey data to examine behavioural and structural factors associated with substance use related disorders, hospitalizations and mortality among GBM in BC. Our results will inform recommendations to improve substance use healthcare for GBM and support reductions in hospitalization costs related to substance.
Walking away from depression: Leveraging physical activity to treat symptoms and improve well-being in individuals with major depressive disorder
Major depressive disorder (“MDD”) is a chronic condition characterized by sadness and loss of pleasure. MDD is a leading cause of disability (WHO, 2020), and costs the Canadian economy billions each year (CAMH, 2021; CASHC, 2016). In 2016, the Canadian Network for Mood and Anxiety Treatment recognized exercise as a first-line treatment for MDD. This statement should have revolutionized care: not only does exercise reduce symptoms, but it also improves health and quality of life. However, the past five years have seen little progress in “mainstreaming” exercise as a treatment option. This means patients are being denied access to a safe and effective treatment.
We are left with a question: How can we get more people with MDD more active more often?
The purpose of my postdoctoral fellowship is to answer this question. I will oversee a program of research that examines how British Columbia’s public health system can provide exercise as a treatment for MDD. I will investigate barriers to uptake; strategies to overcome barriers; and engage in program development and evaluation. This research will be conducted in collaboration with patients, healthcare providers, and communities to ensure it is feasible, relevant, and sustainable.
Mapping the Continuum of Respectful Experiences (CORE) in perinatal care among historically marginalised women and people in British Columbia
Evidence of disrespect and abuse during pregnancy and birth is increasing globally; however, little is known about the experiences of childbearing people in BC and high-quality data is needed, to address this serious issue. While it is essential to ensure a positive birthing experience regardless of the person’s background, research suggests that racialized and minority groups are more likely to report disrespectful treatment by care providers and are less likely to access high-quality care during pregnancy and birth.
In my study, I plan to analyze the pregnancy and birth stories from childbearing people, using several data sources and analysis approaches. Body mapping is a participatory method of data collection that will help to depict experiences of respect, disrespect and abuse. My goal is to create a Continuum of Respectful Experiences (CORE) model to describe complex, multi-layered experiences each birthing person may encounter during perinatal care. This model can be used as a tool to change patterns in care provision. It can teach care providers ways to reduce disrespect and abuse; enable person-centered decision making and understand the needs of people with different identities.
Structural exploration of locked nucleic acids (LNAs) for incorporation into anticancer oligonucleotides
Antisense oligonucleotides (AON) are short lengths of RNA or DNA molecules which are used to change gene expression to treat diseases like cancer and Parkinson’s disease. Like DNA, AONs are made up of chains of nucleotide units, but to make them useful as drugs, these nucleotides have to be structurally changed. Locked nucleic acids (LNAs) are a very useful type of altered nucleotide unit, since they are not broken down as quickly in the body, and attach strongly to the gene they are targeting. The problem with LNAs is that they are very difficult to make, so it is hard for chemists to make a lot of different changes to the structure of LNAs in order to find the best one to use in AONs.
The Britton research team recently discovered a new way to make LNAs very quickly and easily, in large amounts, from simple compounds. Using this new technology, we want to make a large number of structurally unique LNAs and, test them to find the best ones to use in AONs for the treatment of cancer.