Triple-negative breast cancer (TNBC) is the deadliest breast cancer subtype, in part due to lack of targeted therapy. Therefore, there is a need to improve methods that determine if treatment is effective and to develop targeted therapies. Cancer cells reprogram their metabolism to enable tumour growth. In doing so, they release metabolites into blood and urine that can act as signals of tumour and treatment status, known as biomarkers. Rather than assessing treatment effectiveness months after therapy, measuring metabolite biomarkers may allow clinicians to determine response to therapy in real-time and early during treatment. Moreover, metabolite biomarkers can also indicate if a tumour is susceptible to specific treatment, thereby tailoring effective therapy to the individual patient. The proposed research program will determine how tumour metabolite biomarkers can indicate effective response and susceptibility to TNBC treatment. Ultimately, this work will contribute to validating metabolite biomarkers that can be used by clinicians to make informed patient care decisions and improve TNBC treatment.
Research Location: University of British Columbia - Vancouver Campus
Using an equity-informed approach to enhance care for children and youth with a neurological condition in British Columbia
Neurological conditions are a major concern for children and youth, with the potential to affect both physical and mental health. These conditions occur as a result of injury, genetics, and exposures which disrupt the normal functions regulated by the nervous system. Despite the reported rates of neurological conditions in Canada, there are no current estimates of children and youth in British Columbia (BC) living with these conditions. Further, there is a lack of understanding on how this population accesses health care. Therefore, we want to quantify the rate of neurological conditions by exploring the current prevalence of in the BC pediatric population. Second, we will identify the barriers to accessing neurological care, focusing on the social determinants of health. Lastly, we seek to address inequities by investigating the implementation of nursing-led care (i.e., assessment, education, and intervention) for children waiting to access neurological care. This work is equity-oriented, with a focus on underserved groups. Research will be performed at UBC and BC Children’s Hospital with input from key stakeholders across BC to enact knowledge translation, seeking to inform practice and create system level interventions.
Enhancing Early Relapse Detection in Testicular Cancer through Rolling Circle Amplification of microRNA Biomarkers
This project aims to improve the accuracy of early-stage testicular germ cell tumor (GCT) relapse detection in patients through rolling circle amplification (RCA) of plasma microRNA miR371. GCTs pose a significant challenge in clinical management due to the lack of sensitive and specific biomarkers for early relapse detection. Patients are at risk of over-treatment and long-term chemotherapy toxicity that negatively impacts life expectancy and quality of life. Patient blood samples from the BC provincial genitourinary biobank will be used.
Commonly used Polymerase Chain Reaction (PCR)-based detection methods have limitations such as precise temperature control requirements that other isothermal amplification techniques lack. RCA is an isothermal method that is effective in treatment and research applications. The clinical validity of microRNA miR371a-3p has been shown to be a potential biomarker for non-teratoma GCTs. However, the sensitivity of this biomarker in early-stage GCT detection using current PCR methods is low, and more accurate methods to detect smaller amounts of circulating miR371 are needed. RCA result sensitivity will be evaluated against PCR results.
The successful implementation of RCA will validate a more sensitive method for miR371 analysis. This will enhance clinical decision-making, reduce treatment toxicity, and extend the reach and applicability of early GCT relapse detection to resource-limited settings.
Andy Jia is a Master of Science student specializing in Interdisciplinary Oncology at the University of British Columbia (UBC). The project will be conducted in the Nappi Lab at the Vancouver Prostate Centre, which has extensive experience in miR371 analysis.
The Canadian Consortium of Clinical Trial Training Platform (CANTRAIN) and Michael Smith Health Research BC provide funding through the CANTRAIN-CTTP & Michael Smith Health Research BC Master’s Studentship 2023 Award Program.
End of Award Update – December 2024
Results
Our promising preliminary results demonstrated that the RCA method can successfully amplify and detect miR371 samples. Our findings indicate that synthetic miR371 was amplified to significant concentrations, and optimizations to our probe designs improved our results with each modification.
Impact
The project relies on plasma samples from patients enrolled in the provincial Genitourinary Cancers (GU) biobank that have already been collected and analyzed. Hence, the findings of this project can profoundly impact the clinical management of testicular cancer. RCA can be easily implemented in resource-limited settings, including rural areas and developing countries, extending its reach and applicability beyond the laboratory setting.
Potential Influence
The impact of this research project is expected to be significant. The primary expected result is validating a new sensitive method for miR371 analysis that could predict tumor relapse in patients with clinical stage 1 testicular germ cell tumors. This validation will enhance clinical decision-making, improve patient management, and reduce unnecessary treatments, leading to reduced healthcare expenses in British Columbia.
Next Steps
Continued optimization of the RCA protocol will be implemented. Patient samples will be used extensively, and to reach a lower temperature of RCA incubation and ensure accurate detection, new probes will be designed, and different reagents will be tested. RCA implementation with electrochemical biosensors for point-of-care detection will be investigated in depth when a lower temperature of RCA amplification has been successfully reached.
Useful Links
- To learn more about the overarching miR371 project: https://clinicaltrials.gov/study/NCT04435756
- The Nappi Lab website: https://nappilab.med.ubc.ca/
Defining research priorities for trauma-informed design of digital health interventions in sexual health
There has been an increase in the adoption of digital health interventions, especially among people with sensitive and potentially stigmatizing sexual health challenges. While digital health technologies can be convenient and cost-effective, there are concerns that negative online activities could inadvertently trigger emotional trauma among end-user patients. Trauma-informed design has emerged in response to the threats of technology-mediated trauma. Yet, this important field is lacking clear research direction on the best and meaningful ways to conduct research that satisfies the collective interest of all the stakeholders that are typically involved in the design and deployment of digital health interventions. This proposed interdisciplinary stakeholder engagement brings together experts in digital health, trauma-informed care, and patient partners in sexual health to explore research priorities on trauma-informed design of digital technologies. This project will identify key research priorities on trauma-informed design that reflect the collective interest and priorities of the stakeholders.
Sharing knowledge to connect, collaborate and co-create Dementia-inclusive Spaces for Community Access, Participation, and Engagement (DemSCAPE)
The Dementia-inclusive Spaces for Community Access, Participation, and Engagement (DemSCAPE) study is a two-year research project (2021-2023), that brings together researchers, trainees, advocacy organization members and municipal partners in Metro Vancouver and Prince George. The project identified patterns in activities outside the home by people with dementia. It also explored how the environmental features of the neighbourhood influenced participants’ mobility and community participation.
To promote community engagement and increase awareness, we will create educational activities with people with lived experiences and community and municipal partners. These activities will showcase the project findings by video and photo exhibits to the general public virtually. Moreover, we will have two public discussion sessions called World Cafés to encourage conversations, collaborative learning and new ideas with in-person video and photo exhibits and interactive games. Our aim is to enhance understanding of the features of a dementia-inclusive environment and advocate for positive changes.
This project will have a significant impact in increasing awareness of dementia-inclusive communities.
Celebrating World Thrombosis Day: Raising Awareness to Save Lives
Our bodies need to be able to form blood clots after injuries such as cuts; these clots are essential because they keep us from bleeding to death. However, blood clots can also form in parts of our bodies where they are not supposed to. The formation of these “wrong” blood clots is called thrombosis, and is the cause of many life-threatening conditions, including heart attacks, strokes, and deep vein thrombosis (DVT). Thrombosis is the cause of death for 1 in 4 people worldwide. October 13 is declared as “World Thrombosis Day” – a day dedicated to raising awareness and educating the public about thrombosis, how to prevent it, and how to recognize the signs of a medical emergency. The purpose of this Reach Grant application is to support a “Café Scientifique” – an openly accessible and inclusive information session aimed at the general public. Our team of physicians and blood researchers will host a panel discussion on World Thrombosis Day (October 13, 2023) to inform the public about the prevention and management of heart attacks, strokes and other thrombosis-related conditions. A better public awareness of thrombosis will help to reduce thrombosis-related sickness and disability in our communities, and ultimately save lives.
Targeting rural healthcare professionals, trainees and patients in disseminating neuroscience-based research
Ischemic brain injury refers to brain injuries that occur from a lack of blood flow and oxygen delivery to the brain. Current clinical management strategies and therapeutics have shown little effect on patient outcomes. As such, urgent research is ongoing with promising breakthroughs in this field by a multidisciplinary group of researchers in British Columbia. Given the urgency of disseminating research findings, this project will involve knowledge translation activities that target three main groups of knowledge users: a) healthcare providers in rural and remote settings in BC; b) healthcare professional trainees; and c) patients, caregivers and the general public. By undertaking targeted knowledge translation activities to each of these groups, the implementation of research findings will be equitable (for all British Columbians including those from rural settings), long-lasting (healthcare professional trainees will be equipped up-to-date knowledge) and patient-centered (disseminating the findings directly to patients and the public).
Making medications fit for older adults: advancing the science and implementation of deprescribing guidelines
As people age, they can end up taking many medications. Certain medications might have made sense when they were started. But as people get older, some medications may no longer be needed, or may be unsafe. It makes sense to consider stopping such medications. It can be tough for prescribers and patients to decide when and how to stop a medication. From 2014 to 2017, we developed guidelines and resources to help patients and prescribers make decisions about stopping medications. Our guidelines and resources are used in Canada and across the world. However, guidelines and resources need to be up to date with the most current evidence. There also needs to be ongoing strategies to ensure guidelines are used in the real world. This project, led from UBC Vancouver, will first survey patients and prescribers to assess needs and priorities for guidelines on stopping medications. We will then update our guidelines based on needs and current evidence. Finally, we will design knowledge translation materials together with patients and prescribers (called “co-design”), and spread the word about our updated resources. We strive to help patients/prescribers decide when and how to stop medications and improve well-being of older adults.
The contribution of metabotropic glutamate receptor 5 (mGluR5) to impaired control of brain blood flow in Alzheimer’s disease
Alzheimer’s disease is a major crisis and a huge burden on healthcare system. It causes a decrease in memory and affects women more than men. The memory decline in Alzheimer’s is linked to poor blood supply to the brain. The causes for poor supply are unknown but it starves brain cells of essential materials leading to improper function. I will study how a molecule present in the cells of the brain called metabotropic glutamate receptor 5 (mGluR5) contributes to the poor blood supply to the brain and the development of Alzheimer’s symptoms. My group at UBC is interested in mGluR5 because it attaches to the “toxic molecules” commonly found in Alzheimer’s brain. I will use mice sick with Alzheimer’s and samples from Alzheimer’s patients to study how the attachment of the “toxic molecules” to mGluR5 can lead to the short supply of blood to the brain and memory loss. I will also study if the role of mGluR5 in Alzheimer’s is different between males and females. In addition, I will test if the drugs that act on mGluR5 can help Alzheimer’s patients by correcting blood supply to the brain and improving memory. I also will work with patient and community partners to help interpret and communicate my findings and guide future work.
Integration of shared decision-making in heart failure pharmacotherapy
Around 375,000 Canadians live with heart failure with reduced ejection fraction (HFrEF). HFrEF worsens quality of life, and leads to hospitalizations and death. There is no cure for HFrEF, but it can be managed with medications. Many people with HFrEF are unaware of the medications available to treat HFrEF and do not receive the best medications for them. Decision aids are tools that can help inform patients about available treatment options so they can be better involved in shared decisions about their health. This study will be conducted at UBC and will recruit from five Canadian HF clinics. This study will help us better understand what matters most to people with HF when making decisions about their medications, and use this to develop an effective decision aid to support shared decision-making. To do this, we will conduct interviews of people with HF and their healthcare professionals. After this, we will ask people with HF to complete a special online survey called a discrete-choice experiment to understand what matters most to them, and by how much, when making decisions about their HF medications. Then, we will develop a web-based decision aid and test how it improves the quality of medication-related decisions and quality of life.