Bipolar Disorder (BD) is a psychiatric condition that affects about 2 percent of people in BC. Individuals with BD experience extreme changes in their mood, as well as their energy and ability to function. These changes, however, are frequently underreported and unrecognized — especially in youth — which can delay the diagnosis and treatment of BD by several years. Dr. Kamyar Keramatian is a psychiatrist at Vancouver Coastal Health and UBC. His research team, including people living with BD, have developed a virtual group-based educational program for youth at high risk for BD. This program aims to increase knowledge of BD, reduce self-stigma, improve help-seeking and enhance resilience in adolescents and young adults who are at high risk of developing BD. His research will explore the feasibility of implementing this new program throughout BC and how it can help young people with BD to be identified earlier and receive more timely care. By facilitating early identification and treatment of BD, his research can potentially reduce health-care costs and lead to more efficient access to care and service delivery for youth with BD across BC.
Award Partner: Vancouver Coastal Health Research Institute
Portable MRI for multiple sclerosis: Feasibility establishment and technical development for clinical and research applications
Magnetic resonance imaging (MRI) is an important tool for diagnosing and monitoring multiple sclerosis (MS), a disease which affects millions of people. Unfortunately, current clinical MRI scanners are expensive to purchase and operate, have long wait times, and are often inaccessible for people in remote areas or with mobility issues. Recently, the world’s first portable and easy-to-use MRI scanner was developed by a commercial company (Hyperfine), and it will be available at the UBC MRI Research Centre in early 2021. Because this portable MRI scanner has a very low magnetic field and a small size, it has few safety concerns and can be easily brought to people anywhere. This platform will vastly improve MRI accessibility for clinical use, and make large-scale MS research possible. However, the portable MRI scanner’s ability to detect MS lesions in the brain needs to be tested. My project will compare the portable MRI scans with standard clinical MRI scans in terms of image quality for MS brains, and come up with a guideline for the use of portable MRI in MS. This work will be the first application of portable MRI to MS clinical care and research, and the ultimate goal is to bring MRI technology to everyone with equal opportunity.
Artificial intelligence based discovery of estrogen receptor activation function 2 (AF2) inhibitors as the first-in-class therapies for drug resistant breast cancers
Breast cancer (BCa) is the most common cancer and the second cause of death from cancer among Canadian women. While antiestrogens are effective initially, BCas eventually reach a state where they no longer respond to conventional treatments. In a first effort to develop new drugs for resistant BCas, we developed inhibitors with a novel mechanism of action, able to suppress the proliferation of BCa cell lines that do not respond to standard therapies. While promising, better compounds are required for effective treatment of resistant BCa.
Chemical libraries already contain more than one billion of compounds, starting a new era of computer-aided drug discovery. Unfortunately, screening of such amount of chemicals is not yet possible using standard methods due to the required computational resources. To overcome this limit, we have developed an artificial intelligence method, progressive docking, which allows to virtually screen such libraries for the first time ever. In this way, we will be able to discover new inhibitors by evaluating billions of available compounds, in order to improve the outcome of BCa for women in Canada and worldwide.
Unraveling disparate roles of Notch-1 and Notch-2 signaling in bladder cancer
Bladder cancer is the fifth most common cancer, yet it remains understudied and we are only now making strides in understanding it’s molecular make-up. Recently we and others have discovered that loss of the cell surface receptor Notch-1 drives growth of some bladder cancers, while increased Notch-2 activity drives growth of other bladder cancers. Here we aim to determine how Notch-1 and Notch-2 can lead to such differing effects on cancer growth even though they share many features. From this we aim to design a new drug to inhibit Notch-2.
We will:
- Create a mouse model that over-expresses Notch-2 in the bladder. We expect this will cause bladder tumours to form.
- Use advanced techniques to study the differences between Notch-1 and Notch- 2 signaling that make them have such different effects. We will especially investigate how each Notch protein controls the reading of genes in the cell nucleus.
- Develop a new a new drug to inhibit Notch-2 using computer-aided drug design.
End of Award Update – April 2024
Results
We have identified a candidate Notch-2 inhibitor that requires further testing in pre-clinical models before potential testing in patients with bladder cancer.
Impacts
Our work has explained an important pathway that drives growth and progression of bladder cancer in some patients.
Potential Influence
This new inhibitor could represent a novel way to treat bladder cancer.
Next Steps
We will publish the results on Notch when completed.
The effects of balance training with or without cognitive training in older adults with MCI and impaired mobility
Mild cognitive impairment (MCI) is an intermediate stage between normal cognitive function and dementia. The rate of progression of MCI to dementia in older adults has been found to be between 10-12% per year, whereas those without cognitive impairment acquire dementia at a rate of only 1-2% per year. MCI has been linked to poor dual-tasking, impaired balance and functional mobility, and is a significant risk factor for falls. Individuals with MCI need preventive therapies that target both the cognitive and mobility-related outcomes. Dr. Jehu has identified pairing targeted dual-tasking training with balance and mobility training as a promising preventative therapy.
In recent research, balance and mobility training (BMT), and balance and mobility plus cognitive training (BMT+C) programs have been shown to improve dual-tasking and functional mobility in the healthy older adult population; however no previous interventions have targeted dual-task training in individuals with MCI. Dr. Jehu will extend this work to individuals with MCI in order to improve cognitive and mobility outcomes. The BMT and BMT+C interventions will determine whether individuals with MCI can reverse cognitive and functional declines and improve to healthy older adult norms.
The timed up & go (TUG) is a commonly used clinical functional mobility assessment tool. TUG has been shown to be an independent predictor of cognitive decline following an ischemic stroke, and has accurately differentiated between healthy older adults and older adults with MCI. Dr. Jehu aims to use TUG to improve the diagnostic interpretation of important clinical measures used to evaluate individuals with MCI.
Dr. Jehu’s research may serve to improve the interpretation of clinical diagnostic tools, which could revolutionize the prescription of exercise in older adults with MCI and improve the overall interpretation of commonly used clinical assessment tools.
End of Award Update: April 2022
Most exciting outputs
In our study Sex differences in subsequent falls and falls-risk: A prospective cohort study in older adults (Gerontology, 2021), we found that modifiable risk factors related to cognition, physical function, psychological wellbeing, and health status predicted subsequent falls. In males, better mobility was not as protective of falls compared with females. This may be due to males’ poorer executive function, contributing to decreased judgement or slowed decision-making during mobility. These results may inform efficacious sex-specific falls prevention strategies.
Impacts so far
I would not have obtained a position as an assistant professor without my Health Research BC / Vancouver Coastal Health Research Institute Research fellowship. I am confident that the experience I had working with Dr. Teresa Liu-Ambrose provided me with the skills I needed to secure a job.
Potential future influence
During my fellowship, I learned the skills needed to become an independent researcher. Some skills include randomized controlled trial design, implementation science methods, how to conduct systematic reviews, skills in cognitive testing, grant writing, and working with patient populations such as older adults who fall and those with cognitive impairment
Next steps
I am now an assistant professor at Augusta University in Augusta Georgia. I was recently awarded an intramural grant to examine the effects of 6 months of exercise on cognition among people living with dementia. I am thrilled to be leading a team of interdisciplinary researchers and healthcare professionals.
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