Best research practices and honest reporting are cornerstones of science. Society assumes that research is performed carefully and reported openly. But there are unseen threats to science—85% of the investment in biomedical research is avoidably wasted due to poor conduct and reporting of research results. When we rely on science to inform decisions about patient care and health policy, society must strive for reliability in science.
Only 3 out of every 100 clinical trials conducted in Canada between 2009 and 2019 provided enough information for researchers, clinicians, patients and policymakers to decide whether the research is meaningful and worth implementing in practice.
I will lead a project to develop and evaluate an online training programme that aims to teach researchers how to maintain an accurate public record of their research—from its beginning all the way through to sharing the results with the scientific community and the public. The training program will roll out across at least 12 universities (out of 16) in British Columbia and culminate in testing how well researchers and institutions in British Columbia register and report the results of their research.
The avian influenza virus H5N1 is shed in infected birds’ saliva, mucous, and feces. Still, other infected animals may shed bird flu viruses in respiratory secretions and other body fluids (e.g., cow milk). The virus can spread rapidly through poultry flocks and among wild birds. Thus, developing diagnostic tests to identify the virus at early stages before dissemination is crucial to contain a pandemic at early stages.
Detecting pathogens during a pandemic has mainly been based on PCR amplification. Although PCR is relatively fast, samples must undergo a lengthy extraction process, especially for environmental samples. Sequential sequencing also requires highly trained personnel, expensive equipment, and specialized facilities. Thus, the current project will develop a rapid test for the surveillance of H5N1 in human communities, point-of-care settings, animal farms, water supply, sediments of wetlands, farming- and human-derived sewages, animal processing plant sewage, and personnel working in animal husbandry.
The project will take place in BC. The project will develop engineered antibodies against the virus H5N1. These antibodies will be used to generate a rapid test. Samples from different environments, such as water supply, sediments of wetlands, farming- and human-derived sewages, animal processing plant sewage, etc., will be sampled, analyzed, and validated by the BCCDC using PCR techniques. The impact of the rapid test will be a fast delivery across the province for the early detection of the H5N1 virus to contain the dissemination and allow better management of the disease.
Sudden cardiac arrest (SCA) is a major health issue where the heart unexpectedly stops beating, and blood no longer circulates through the body. In Canada, there are about 60,000 cases of SCA each year. Quick action, such as starting cardiopulmonary resuscitation (CPR), is crucial. The longer it takes to start CPR, the less likely a person is to survive. Unfortunately, most SCAs happen in places where no one is around to help. Therefore, one of the biggest challenges in improving survival rates is the delay in recognizing that a cardiac arrest has occurred. Consumer wearable technologies have great potential to continuously monitor cardiac function and automatically recognize signs of disruption or loss of blood circulation at any time. If a problem is detected, these devices could automatically call emergency services for help. Our previous studies have shown that wearable sensors combined with artificial intelligence (AI) can recognize some signs and symptoms associated with a cardiac arrest, such as absence of a pulse. The overarching goal of the proposed project is to validate the performance of such a system for real-world SCA detection.
Infants born extremely prematurely, especially before 26 weeks’ gestational age (GA), are classified as micropreemies and are considered the most vulnerable population. These babies often face serious short and long-term health challenges. One common problem is intraventricular hemorrhage (IVH), a type of brain bleed that remains the leading cause of death in this vulnerable population. Severe IVH (sIVH) can lead to significant lasting effects such as cerebral palsy, reduced IQ, and overall neurodevelopmental disabilities. Clinical trials have shown that preventative indomethacin, a nonsteroidal anti-inflammatory drug, can prevent sIVH and death. In Canada, babies born before 26 weeks’ GA from 2018-2022 who received indomethacin had a 5% lower death rate and were 4% more likely to survive without sIVH in comparison to those who did not receive the drug. Although past studies have shown that prophylactic indomethacin can reduce both sIVH and death, its use in clinical practice remains inconsistent due to concerns about potential negative effects. The proposed study, PRophylactic Indomethacin in MicropreemiEs (PRIME), specifically examines the impact of prophylactic indomethacin on short- and long-term neurodevelopmental outcomes in the micropreemie cohort. The pan-Canadian retrospective observational study will link data from the Canadian Neonatal Network and Canadian Neonatal Follow Up Network to investigate the relationship between preventative indomethacin and death and disability in extremely premature infants. Additionally, neurodevelopmental outcomes will be explored at 18-24 months. Una Spasovski, a master’s student in the Women+ and Children’s Health program at the University of British Columbia, will lead this study in British Columbia. Under the supervision of Dr. Souvik Mitra, her research specifically focuses on improving outcomes for extremely premature infants at the BC Children’s Hospital Research Institute.
One of the most devastating consequences of cervical spinal cord injury (cSCI) is the loss of hand movements, which severely impacts independence and quality of life. Nerve transfer surgery (NT) is emerging as a promising method to restore functions like hand opening and closing. While previous research shows NT is safe and potentially effective, robust scientific evidence of the effectiveness of NT is lacking. To address this gap, a national collaborative effort led by BC-based physiatrist and clinical assistant professor Dr. Michael Berger is conducting the first multi-centre prospective study on NT for individuals with cSCI (https://clinicaltrials.gov/study/NCT05638191). The primary aims of this study are to evaluate NT’s overall effectiveness in individuals with cSCI, identify patient subgroups most likely to benefit from NT based on factors like age and injury level, and explore patients’ lived experiences post-surgery. This study, supported by the CANTRAIN-CTTP & Michael Smith Health Research BC Post-Doctoral Fellowship 2024 Award Program, is being conducted across four Canadian interdisciplinary clinical programs (Vancouver, BC; Toronto, ON; Kingston, ON; Halifax, NS). Over four years, participants will undergo comprehensive assessments at baseline and regular intervals for 24 months post-surgery, enabling researchers to track changes in functional, motor, and patient-reported outcomes. By rigorously evaluating the efficacy, safety, and broader impacts of this innovative surgical technique, our team aims to provide individuals with cSCI the knowledge and confidence to make informed decisions about their treatment options.
Head and neck cancer is the seventh most common cancer worldwide, with over 660,000 new cases and 325,000 deaths each year. After removing a tumor, a common reconstructive method called Free Tissue Transfer (FTT) is used. This involves transplanting skin, muscle, or bone, along with its blood supply, from one part of the body to the surgical site.
A proper blood supply to the transplanted tissue is crucial. If blood flow is inadequate, complications or tissue death can occur, which may require further surgery or even lead to death. Early detection of changes in blood flow and oxygen levels is key to preventing these issues.
Currently, FTT monitoring relies on hourly visual checks by trained medical staff, which are subjective and not continuous. To address this, our team has developed an optical non-invasive sensor using near-infrared spectroscopy (NIRS). This technology uses light to measure blood flow and oxygen levels in the tissue. It provides a metric called Tissue Oxygenation Index (TOI), which reflects the health of the transplanted tissue.
Initial testing on four patients showed the sensor could monitor tissue oxygenation continuously for 72 hours after surgery. Amir’s project aims to enhance this technology by creating a wireless, non-invasive sensor. It will transmit data to a monitor and remote systems, allowing doctors to track patient status and receive alerts if TOI changes.
The next steps include clinical trials with 60 FTT patients to establish TOI baselines and improve the sensor’s hardware and software. The device recently received approval from Health Canada and Clinical Trial governments body. This innovation aims to reduce FTT failures, improve patient outcomes, and lower healthcare costs.
Cancer cells develop ways of escaping and hiding from the immune system so that they are not recognized as unhealthy cells. If our immune cells could recognize the abnormal cancer cells growing in the body they would attack and kill the cancer cells. A big problem is that we don’t know enough about how different types of immune cells regulate their response to tumor cells; so we don’t how to manipulate the system to get the immune cells to engage and attack the tumor. One way that immune cells regulate their response to tumor cells is through the binding of sugars, called glycans. Glycans on immune cells and on tumor cells have been shown to be critical in the regulation of the anti-tumor immune response. Recently, we discovered unique glycan on immune cells in the breast tumor microenvironment. Patients whose tumors had high levels of this glycan on immune cells had worse survival outcomes. We think that this glycan controls the immune response and when expression levels are high, it prevents immune cell activation. To study how this glycan regulates the anti-tumor response, we propose to identify the immune cell subsets carrying this glycan and then study how this glycan effects their tumor killing functions. Our work will provide important details to help us understand how to trigger the anti-tumor immune response and may provide a new immune-checkpoint target for therapeutic development.
Unlike ‘liquid’ leukemias and lymphomas, most solid tumors are extremely difficult to target immunologically with antibody-based therapeutics. In an effort to overcome this limitation, we identified a novel peptidoglycan on the surface of aggressive solid tumor cells that are present in multiple cancer types. These include breast, ovarian, bladder, colorectal and oral squamous carcinomas as well as glioblastomas. Molecularly, this peptidoglycan is found on the extracellular domain of the cell surface mucin ‘podocalyxin’. Biologically, the emergence of the podocalyxin peptidoglycan is exquisitely tumor-specific and we have demonstrated that it can be successfully targeted immunologically in pre-clinical solid tumor assays in a manner that spares normal cells and tissues. This has been achieved using an antibody drug conjugate against the podocalyxin peptidoglycan that we have developed.
In this project, we will first use genome-wide editing screens to identify regulators of the tumor-specific podocalyxin peptidoglycan using CRISPR Cas9 technology. In preliminary proof-of-principle experiments we have identified twelve potential regulators from four different functionally-clustered intracellular signaling complexes. We will next manipulate such regulators, both genetically and pharmacologically with small molecule inhibitors, to precisely tailor the immuno-oncologic targeting of aggressive podocalyxin peptidoglycan-positive solid tumors. Finally, we will take a glyco-proteomic approach to identify additional tumor-specific peptidoglycans that can also be targeted immunologically. The overarching goal of this project is to develop a pipeline of novel antibody-based immuno-therapeutics that can be used to treat multiple aggressive solid cancers with precision and minimal side effects given that they will, by design, spare normal cells and tissues.
Stimulants (i.e. cocaine and methamphetamine) are increasingly detected in drug toxicity (i.e. overdose) deaths in BC. Our recent analyses reveal high rates of chronic disease among people who have died of stimulant and;or opioid overdose in BC. For example, we identified high rates of heart disease and mental illness among people who experienced stimulant overdose. These analyses suggest possible opportunities for intervention across the health system in chronic disease care, to reduce overdose risk.
At the Provincial Health Services Authority, a new data platform holds health records for emergency department visits, hospitalizations, and primary care visits for all BC residents. In the context of rising stimulant use in BC, and this new data source, there is an opportunity to use these data to fill knowledge gaps on stimulant use and overdose risk in BC.
We aim to address this knowledge gap by bringing together a group of people with lived and living experience of stimulant use to form a Peer Advisory Group. The group will advise on how these data can be used to investigate the intersections of chronic health conditions and overdose risk, with attention to the specific risks faced by people who use stimulants.
The impact of cannabis access and use on the development of high-risk substance use behaviours remains controversial during the opioid overdose crisis. To address this knowledge gap, I plan to:
1. Identify how cannabis access and use impact early substance use careers, including the use of opioids, stimulants and injection drug use among at-risk youth;
2. Analyze how cannabis access and use impact overdose, as well as risk factors for overdose (e.g., binge opioid use) among high-risk subgroups of people who use drugs (e.g., people with chronic pain, HIV);
3. Characterize how cannabis use impacts engagement and effectiveness of addiction treatments. We will also investigate how cannabis use intentions (e.g., recreational vs. therapeutic use) shape addiction treatment outcomes.
This project will analyze data from three studies (N=3,375) of people who use drugs (PWUD). Established partnerships with the BC Ministry of Health and community groups of people with living experience of substance use will support the production of scientific evidence, policy briefings and community resources that will be important to inform clinical and public health practice, as well as policy responses to the overdose crisis during the fentanyl era.
