Evaluation of a manualized telehealth-based psychoeducation group for individuals at high risk for bipolar disorder

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.

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.