Exogenous ketone body (KB) ingestion is an emerging therapeutic strategy for combating the harmful health conditions associated with type 2 diabetes (T2D), including a heightened risk for neurological disease and cognitive decline.
Evidence from animal models and early studies in humans supports its potential; however, high-quality research trials examining the effect of KB ingestion on brain function in humans with T2D have not been performed.
Dr. Walsh’s research will investigate the acute (single dose) and short-term (14 day) effects of KB supplementation on aspects of brain function in people with T2D, including measures of cognition (i.e., memory and attention) and circulating growth factors related to cognition.
The results of this research will help determine the therapeutic potential of exogenous KB supplementation for improving brain, vascular, and metabolic health in people with T2D.
Resistance training has been shown to improve myriad health indicators, including quality of life, in people with rheumatoid arthritis (RA). However, resistance training participation rates among people with RA are remarkably low (1-14%), even in those with well-controlled disease. Anecdotally, unique barriers exist that prevent those with RA from participating in resistance training, including fear, health care provider knowledge, and functional limitation.
Resistance training-specific promotional efforts are sorely needed; however, understanding and research into changing resistance training behaviours is only in its early beginnings. The barriers to participating have yet to be scientifically explored and the state of behaviour change theory testing in resistance training behaviour is almost non-existent.
Dr. Ma’s will conduct a four-phase study to better understand the barriers and facilitators to resistance training, select promising behaviour change theories, and develop knowledge tools proposing resistance training interventions. The overarching aim is to launch the field of resistance training behaviour change, aid the uptake of guidelines, and improve health outcomes for patients with RA.
Inflammatory bowel disease (IBD) is characterized by chronic, relapsing inflammation of the gastrointestinal tract, and includes Crohn’s disease (CD) and ulcerative colitis (UC).
The gold standard induction therapy for treating active pediatric CD is “exclusive enteral nutrition” (EEN), which is a nutritionally complete liquid diet provided by tube feeding that excludes normal food intake. This nutritional strategy is superior to standard induction therapies; however, treatment must be maintained for 6-12 weeks to induce remission, and relapse rates are high after stopping EEN.
To date, EEN in pediatric patients with UC has not been shown to be effective and as a result is not regularly used. Also, the standard enteral formula does not contain fibre and is low in vitamin D, even though both factors lead to beneficial changes in gut bacteria and reduce inflammation in IBD.
Dr. Healey will recruit pediatric CD and UC patients to determine if enteral formula with fibre and concurrent oral vitamin D3 improves IBD beyond standard EEN and medications. Her research will also include undertaking animal studies to explore the mechanisms of this novel EEN strategy. The results of this research could lead to improved treatment strategies and outcomes for children with IBD.
Youth with obsessive compulsive disorder (OCD) often experience distressing experiences (for example, unwanted thoughts) which they try to prevent or relieve through obsessive strategies such as repeated hand-washing. Without treatment, OCD tends to remain a problem for youth and makes their lives very difficult.
Cognitive behavioral therapy (CBT) has been shown to reduce symptoms and improve quality of life for most youth with OCD. However, CBT is a broad term that can include different strategies and exactly which strategies are the best to use has not been carefully studied.
Dr. Selles’ research will involve implementing a five-day intensive CBT program for youth with OCD, comparing two different strategies for youth and two different strategies for therapist involvement. This study will examine how well the treatment works and compare the impact of these strategies on symptoms, child and family wellness, family preference, and cost.
This research will help bring a needed clinic service to British Columbia while providing therapists with clearer ideas about how to provide treatment in a way that will benefit youth with OCD the most.
Dementia with Lewy bodies is the second most common form of dementia following Alzheimer’s disease. This disease can be challenging to identify because symptoms can resemble those of Alzheimer’s disease, Parkinson’s disease, and/or mental illness. Currently, there is no test that can spot dementia with Lewy bodies and the only way to confirm the presence of this disease is by autopsy.
In this type of dementia, deposits known as Lewy bodies accumulate in the brain. Lewy bodies are formed by a protein inside neurons called alpha-synuclein. Alpha-synuclein is also found in cerebrospinal fluid, which is the fluid surrounding the brain and spinal cord. While we know that alpha-synuclein in cerebrospinal fluid is helpful for distinguishing dementia with Lewy bodies from Alzheimer’s disease, further work is needed to improve this test.
The goal of Dr. Singh’s research program is to develop a test that can identify dementia with Lewy bodies and distinguish and the disease from Alzheimer’s. She will create a diagnostic tool for clinical use to measure alpha-synuclein, and also explore modifications of alpha-synuclein that occur in disease that could improve our ability to identify dementia with Lewy bodies.
Myocarditis is defined as inflammation of the heart muscle, most often associated with viral infections. While the true occurrence of myocarditis is difficult to establish, it affects all ages and sexes and is a major cause of sudden death in young people.
Recognizing myocarditis in the clinic is challenging. Current tools for making a diagnosis are invasive (requiring access to heart tissue) and imprecise, leading to poor patient outcomes. Any delay in proper diagnosis may lead to dramatic measures like heart transplantation to ensure patient survival.
The goal of Dr. Hanson’s research is to develop tools to diagnose viral myocarditis more precisely, allowing for each patient to be treated in a timely fashion and on an individual basis. This will include applying knowledge from mouse models of viral myocarditis to humans. In these models, Dr. Hanson has so far discovered increased amounts of certain proteins in myocarditis hearts when compared to unaffected hearts. Previous work suggests these markers could improve our ability to identify patients with myocarditis, and may reliably distinguish those patients with viral infection in the heart muscle from others with inflammation but no infection.
This research will improve insight into what happens at the level of molecules during viral myocarditis, potentially identifying new ways to treat the disease. Ultimately, leading to the development of a non-invasive blood test to diagnose myocarditis, personalizing how patients with myocarditis are treated and managed.
Antibiotics revolutionized our medicine against pathogen infection. However, pathogenic bacteria have recently evolved resistance to multiple antibiotics, becoming a global health care risk. We urgently need to develop novel strategies to combat antibiotic resistance and develop evolution-proof antibiotics.
Dr. Han’s research will study and engineer enzymes that could be used as potential antibiotic reagents to degrade a key chemical molecule that bacteria utilize to develop virulence and resistance to antibiotics (biofilm formation). Specifically, Dr. Han will look to discover novel enzymes and perform detailed profiles of these enzymes to interpret their molecular mechanisms. Using state-of-the-art enzyme engineering and laboratory evolution techniques, he will engineer these enzymes for higher stability and functionality and demonstrate anti-virulence and anti-biofilm capabilities of these engineered enzymes, crucial for biotechnological and pharmaceutical applications.
This research program will provide the first mechanistic study of enzymes that disrupt the virulence of diverse pathogenic bacteria, and could have significant impact in the field. Most importantly, this research could provide novel and effective tools to control bacterial population and infection, crucial in the fight against the development of antibiotic resistance.
Prostate cancer is the second leading cause of cancer death. Comprehensive analysis of genomes has the potential to inform precise prostate cancer treatments. However, a major challenge of prostate cancer genomic analysis is the inaccessibility of metastatic tissue. Circulating tumour cells (CTCs) offer great potential as an alternative source of genetic material, which would enable the identification of the relevant mutations and aberrations that define prostate cancer subtypes.
Despite the tremendous potential of CTC genomics, there has been little progress in genotyping CTCs. This is due to the rarity of CTCs and their genetically heterogeneous population. Current methodologies have overcome this limitation by performing single-cell sequencing. However, existing methods for single-cell isolation require precise manipulations using contaminant-free tools, which are either extremely difficult to perform or are associated with unacceptable cell loss.
Dr. Choi’s research will look to develop a new method to rapidly target and select single CTCs based on their phenotypic profile. This method would enable both in situ immunostaining and single cell sequencing, which would provide important insights when interpreting data from genetic analysis.
The results of this research could be significantly beneficial in the development of personalized therapy, evaluation of anti-cancer drugs, and surveillance for disease recurrence.
Epilepsy is one of the most common brain disorders. The condition is characterized by uncoordinated brain electrical activity and recurrent seizures. Epilepsy patients may die unexpectedly with unknown cause, a phenomenon termed “sudden unexpected death in epilepsy” (SUDEP). SUDEP accounts for about 50% of deaths in individuals suffering from drug-resistant epilepsy in which severe seizures are followed by alterations in respiratory and cardiac functions.
The underlying mechanisms triggering SUDEP remain unknown. Using animal models of human disease and live brain imaging, Dr. Thouta’s research will work to define the specific brain regions that promote brain inactivity during SUDEP-like seizures. This will include testing novel anti-epileptic drugs as a potential preventative SUDEP agent.
The results of this research will provide an understanding of the cause of SUDEP and could have a significant impact on epilepsy drug development efforts, potentially leading to the discovery of novel therapeutics for SUDEP prevention.
The dispersal of tumour cells within malignant tissue relies on a process called chemotaxis, where tumour cells migrate in response to chemical signals in the local microenvironment. There has been longstanding interest in using chemotaxis assays to deduce how invasive a tumour is, and how it might respond to drug therapy. However, current chemotaxis assays are prone to extreme inter-assay variability, due to the inherent instability of the chemical gradient. Additionally, existing assays require a large number of cells, making it impossible to test primary patient tissue, which typically only yields a few hundred tumour cells.
Dr. Park’s research will work towards developing a microfluidic platform to generate highly stable and uniform chemical gradients for the chemotaxis assay of a small number of tumour cells. She will validate the technology by examining the response of cultured tumour cells to chemotherapy. Cells from murine tumour xenograft will further establish the relationship between migration with disease progression and drug-efficacy.
The results of this research could provide a reliable means to evaluate the migratory potential of patient tumour cells both before and in response to therapy, ultimately guiding clinical decisions in practice and within personalized clinical trials.
