Fucosylation inhibitors for convenient production of fucose-deficient antibodies

Therapeutic antibodies have revolutionized the treatment of cancers. The efficacy of many of these antibodies depends on their ability to recognize and bind to cancer cells. These antibodies then recruit immune cells to kill the cancer cells. Recent interest has focused on the different sugar molecules attached to the antibody and their role in helping or hindering the recruitment of immune cells. Specifically, eliminating one specialized sugar known as fucose from antibodies dramatically improves their ability to recruit immune cells and kill cancers. Industry is therefore interested in ways to prevent this sugar modification and to thereby produce improved anti-cancer antibodies.

We have developed a new family of chemical compounds that block the addition of fucose onto antibodies as they are being produced. We now aim to translate this work to drive the generation of improved therapeutic antibodies. Because the fucose-deficient antibodies are much more potent, it is expected that lower doses of these antibodies can be used leading to a lowered risk of side effects. Additionally, the increased potency should lead to improved efficacy of therapeutic antibodies and outcomes for cancer patients in British Columbia and elsewhere.

Evaluation of innovative risk mitigation services in the context of dual crises of COVID-19 and overdose among people who use opioids in Vancouver, BC

Through funding from the Canadian Institute of Health Research (CIHR) and MSFHR, Principal Investigators Dr. Kanna Hayashi, Research Scientist at the BC Centre on Substance Use (BCCSU) and St. Paul’s Hospital Chair in Substance Use Research and Assistant professor in the Faculty of Health Science at Simon Fraser University (SFU) along with Dr. Kora DeBeck, Research Scientist at the BCCSU and Associate Professor in the SFU School of Public Policy aim to conduct preliminary evaluation of two novel measures introduced by the BC government in March 2020 to address the dual crisis of overdose and COVID-19.

Specifically, these measures include expanding the opioid agonist treatment (OAT) prescription guidelines and pandemic prescribing of pharmaceuticals (e.g. opioids) to people who use illicit drugs. By providing pharmaceutical alternatives to the toxic illicit drug supply, the interventions are intended to reduce physical encounters involved in obtaining illicit drugs and the use of toxic street drugs, thereby supporting both overdose and COVID-19 prevention efforts. To date, however, the impacts of these interventions have not been evaluated.

The proposed BC-based research aims to fill critical knowledge gaps by examining the reach and preliminary impacts of pandemic prescribing and expanded OAT prescription services among people who use opioids in urban Vancouver. Through this work, the research team, which consists of highly productive investigators and knowledge users with direct clinical and policy expertise, seeks to inform efforts to improve the delivery and effectiveness of the interventions.

Funding Competition: CIHR Operating Grant: COVID-19 Mental Health & Substance Use Service Needs and Delivery Funding Opportunity

Funders: CIHR; MSFHR

Determinants of sexual and reproductive health care for im/migrant women: a community-based mixed methods study to realize comprehensive primary care in BC

Primary care is key to a working health care system. Good primary care is based on relationships with a provider who knows a patient over time and sees the whole person in context, so they can address social needs that particularly impact the health of marginalized groups. Although im/migrants are a big part of the population in Canada, they have less access to good primary care. We use ‘im/migrant’ including all people that arrive in Canada from another country, including refugees, economic and undocumented im/migrants. Some groups (refugee claimants, precarious status) have even more limited access to primary care and may face worse health. This is especially true for im/migrant women of reproductive age. An important feature of primary care is sexual and reproductive health (SRH) care, like contraception, cervical cancer screening, and pregnancy care. We can learn about and improve primary care for im/migrant women by looking at their experiences with SRH. Guided by im/migrant women, this project uses interviews and information from the health system to describe their SRH within primary care in BC. This will produce collaborative solutions for SRH in primary care that promote equity for im/migrant women and families in BC.

Genome-wide screen to identify genetic modulators of glucocerebrosidase activity

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Despite PD affecting millions of people worldwide, no disease-modifying treatment is available yet. As the progress of the disease is closely related to aging, improving our knowledge of the mechanisms and factors leading to PD is of great interest. Mutations in the gene GBA, which encodes the enzyme glucocerebrosidase (GCase), are the greatest genetic risk factor for PD. The link between GCase and PD however, remains poorly understood. Here, we propose to use a chemical genetic screening approach to identify new genes that affect GCase activity. As a pilot study, we will target known PD-associated genes and evaluate their effects on GCase activity using a new GCase activity-based assay in live cells. A complementary approach using genome-wide screen will be carried out to identify candidate genes in an unbiased way. Candidate genes from these screens will be validated with downstream experiments leading to two valuable outcomes. First, the discovery of new genes that regulate GCase could provide new targets for potential treatments. Second, we expect these findings will uncover new fundamental understanding regarding the mechanisms contributing to PD.

Mental health in later life: A stakeholder-informed approach to health and technology interventions for older adults

Feeling down or worried happens to everyone, but for some people these feelings are very strong, long-lasting, and can be damaging to them and their families. Mental illnesses, such as depression or anxiety, may include feelings of hopelessness, helplessness, guilt, or even suicide. Worldwide, mental illness affects one in five people aged 60+.

However, problems faced by older adults impacting their mental health are often overlooked, such as loneliness, loss of a spouse, or ill-health. We need to change the way we treat mental health, with services that consider older adults' specific needs and situations.

To this end, we will bring together an advisory board of older adults to help inform the project, providing insights into what contributes to their mental health and what sorts of technologies promote better mental health. Using these insights we will identify factors that contribute to older adults’ poor mental health. 

Additionally, we will work with older adults to test technology-driven interventions, for example mobile apps, that best suit the needs of older adults in improving their mental health.

Healthy Children, Healthy Communities: Co-Benefits of Children’s Action on Climate Change and Mental Health

Problem: British Columbia is being increasingly impacted by climate change and therefore the health and wellbeing of children in this region are at risk, and will be throughout their lives unless action is taken.

Overview: Conducted for, by and with children, this research will answer 2 questions: How is children’s health being impacted by climate change? Can taking action on climate change through community projects, strengthen and build resilience in children, even in the age of climate change? A central focus of this work will be on mental health and wellbeing.

Outcomes: After filling a significant scientific knowledge gap about the public health impacts of climate change on children in BC, evidence gathered will be used to help develop community projects that tackle a local impact of climate change.

Impacts: This research will identify why and how certain community projects on climate change protect, and even improve, the mental health and wellbeing of children and make recommendations for how other communities can use this information to build their own healthy children, healthy community projects. These successes will be shared with decision makers to support the choices they make around climate change and health.

Real-time Combined Genomic and Epidemiological Monitoring of COVID-19 in British Columbia

Viruses accrue small amounts of genetic variation over time. By sequencing the virus, we can see this variation and use it to understand where an individual virus likely came from and how it is moving through a population. This helps public health teams to estimate how many cases are due to local transmission as opposed to imported cases. In this proposal, we will establish ways to use virus sequences to understand transmission in a high-resolution way that is not possible with epidemiological or virus sequence data alone. To do this, we will combine viral sequences with epidemiological data in new ways, establishing high-resolution pictures of transmission. We will operationalize the use of these combined datasets for real-time COVID19 public health use in BC.

Preventing and Mitigating the Impacts of COVID-19 Among Im/migrants in British Columbia: Rapid Mixed-Methods Data to Inform Policy and Programmes.

In BC, migrants make up >25% of residents and are overrepresented in crucial roles as essential workers (eg, temporary foreign workers), yet may be disproportionately impacted by COVID-19 and face barriers to healthcare access. Despite purported shifts to ‘universal’ coverage for COVID-related care, many im/migrants report severe ongoing inequities, including gaps in healthcare coverage, unsafe living/working conditions, and confusion about how changes are put in practice. Rapid transition to virtual service delivery may also compound inequities due to language or technology barriers. We will use health system data and interviews to understand migrants’ experiences with COVID-19 related care and health services coverage to ensure “no one is left behind” in the COVID-19 response and beyond.

“Blind Spots”: People in Prison and Precarious Housing During COVID-19

Prisons and substandard housing pose serious risks to individuals and communities during the COVID-19 pandemic. Limits on physical distancing are associated with disease outbreaks in shelters, camps, and prisons. The high prevalence of pre-existing illness in the settings places people at risk for medical complications. This project will generate evidence of ways to reduce the spread and impact of COVID-19 by analysing hospitalizations among people who were in custody or inadequate housing during the first wave of COVID-19 in BC. The project will also develop recommendations on the use of mandatory testing. The project team is drawn from established networks of researchers, decision-makers, service providers, and people who have experienced homelessness and time in custody.

A Spatial Approach to Exploring Vulnerability in the Context of COVID-19 in British Columbia

Maps are an excellent way of simply communicating complex ideas. We will create maps that use sophisticated analysis techniques and draw on multiple information sources. Our maps will tell decision-makers where in BC they should focus COVID-19 mitigation efforts and other interventions. Drawing on population and location factors, our maps will show where in BC people are vulnerable to developing COVID-19 infections, where people are vulnerable to experiencing challenges to accessing ICU care for complex COVID-19 cases, and where people are vulnerable to experiencing health-related secondary impacts of the pandemic. We will work with officials to identify ways to improve our maps and integrate new evidence. Will also make maps they request to support their decision-making.