The ADAPT Project: Adaptation, Development, and Positive Trajectories in the context of childhood adversity

Over half of Canadians have experienced at least one childhood adversity (CA), which is linked to an increased risk of poor health and wellbeing across the lifespan. Current approaches have focused on linking CA to poor outcomes, yet this approach overstates the impact of risk and devalues the importance of protective factors enabling individuals to withstand, adapt, and recover. The focus on outcomes may also fail to capture the trajectories of wellbeing and cyclical nature of resilience and vulnerability.

This program of research utilizes a mixed-methods approach to explore pathways to wellbeing in the context of CA, focusing on the timing and type of protective factors. To fully understand how socio-environmental and biological factors contribute to health and wellbeing inequity due to CA, we must examine the pathways to impairment and wellbeing using a developmentally informed framework. Changing the question from ‘how are youth at risk’ to ‘how do youth adapt,’ and shifting to a model where those with trauma histories are not defined by their risk. Findings will produce actionable evidence for practitioners and policymakers to develop early intervention and prevention programs fostering health equity for those with CA.

Systems transformation for health equity: The PHAIRNESS Research Program

There are growing differences in health among population groups due to unfair social conditions that disadvantage some people more than others in British Columbia and beyond. Health systems play a role in holding this problem in place by presenting unnecessary barriers to accessing quality healthcare. Health systems also have a key role in closing these gaps by taking action to change the underlying conditions that shape health and wellbeing. The Population Health Approaches to Implementing Research (k)Nowledge for Equitable Systems & Strategies (PHAIRNESS) Research Program aims to make visible and intervene on systems-level problems in three connected systems: health systems, surveillance systems and research systems. By working closely with health systems, communities and people who are impacted by these issues, research findings will be relevant, useful, and ready to be rapidly applied to improve health systems and support the wellbeing of all people in British Columbia.

Evolutionary mismatch: a cause of cardiovascular disease in industrialized societies?

In the Origin of Species, Charles Darwin presented that species evolved to best suit their environments. Endurance exercise was central to the extensive hunting and gathering of early human ancestors. To support prolonged exercise in the heat, the cardiovascular system must work hard to keep the body cool and to provide blood to exercising muscles and the brain. Thus, having a cardiovascular system that supports endurance activity in the heat would have been beneficial to early humans. In stark contrast, humans in postindustrialized societies live in temperature-controlled, sedentary environments. Cardiovascular disease is the leading cause of death worldwide; however, it is extremely rare in preindustrialized societies, such as modern hunter-gatherer and subsistence farming populations. This project aims to investigate cardiovascular aging from an evolutionary lens. Over the next three years, we will compare vascular structure and function in semi-wild chimpanzees, hunter gatherers in Tanzania, subsistence farmers in Mexico, and sedentary residents of British Columbia. The results will help us to understand what normal cardiovascular aging in humans is.

Understanding counsellor-client interactions in spinal cord injury exercise counselling: a novel method to explain outcomes of randomized controlled trials by assessing intervention fidelity

Behavioural interventions often consist of conversations between counsellors and clients and can be a successful way to promote a healthy lifestyle. However, controlled intervention outcomes are not always successfully translated to real-world settings. A possible reason for this poor translation, is that researchers do not use information on how counsellors and clients interact with each other to explain intervention outcomes. Recently, a new method, called state space grids, has been developed to study and visualize how a counsellor and client interact with each other over time. This study will use state space grid methods to study conversations about health-enhancing exercise between counsellors and clients with spinal cord injury (SCI) to explain health outcomes. Participants receive tailored exercise counselling. Recordings of the sessions will be analysed using state space grids. The findings will help us to better study and understand how, when and why counselling is successful in changing health behaviour. These new insights can be used to develop training guides for counsellors and improve exercise counselling. In turn, understanding and improving effective exercise counselling will enhance lives of many people with SCI.

A novel strategy to mitigate secondary hypoxic injury following traumatic spinal cord injury through the augmentation of local microvascular oxygen supply

There are approximately 2000 new cases of traumatic spinal cord injury (SCI) per year in Canada, with an associated health care cost of more than $1,500,000 per patient over a lifetime. The severity of SCI is compounded by injury processes that arise following initial trauma, which are related to a reduced oxygen supply to the injured spinal cord tissue. This process, where oxygen supply is reduced, is modifiable and therefore an ideal target for treatments aiming to improve outcome in SCI patients. Despite the potential to improve oxygen supply to the injured spinal cord, current treatments have yet to demonstrate notable efficacy. This is because it is difficult to alter oxygen supply to the spinal cord without causing undesirable changes in a patient’s blood pressure. We will utilize novel breathing strategies to target a specialized blood flow control mechanism to improve oxygen delivery to the injured spinal cord in rodent models of SCI. Further, we will characterize the function of this blood flow control mechanism in SCI patients, which will allow us to establish the potential efficacy of an exciting new avenue for improving outcomes and reducing healthcare burden after SCI.

Plant based anticancer drugs – from discovery to final products

Plants are endowed with biological catalysts (enzymes) that make natural drugs used to treat various human illnesses. Among these, the Chinese happy tree (Camptotheca acuminata) produces the anticancer drug camptothecin. Although camptothecin is readily convertible to the more potent drugs topotecan (Hycamtin) and irinotecan (Camptosar), this requires chemical synthesis steps which rely on toxic chemicals and petroleum-based resources.

Our research program aims at developing  multidisciplinary approaches to discover and modify happy tree’s enzymes that facilitate the production topotecan, irinotecan and new camptothecin-derived analogues. We aim to rapidly generate 25-50 camptothecin-derived analogues by biotechnological means and test these compounds using in vitro and cellular assays to assess potential anti-cancer activity.

Our biosynthetic approach will allow us to explore the untapped medicinal potentials of a whole host of novel camptothecin-related chemicals in addition to topotecan and irinotecan. Long-term efforts, also ongoing in our laboratory, will focus on synthetic biology approaches to scale up production of compounds that show promising bioactivity.

Molecular Tools for Monitoring and Controlling the Mechanobiology of Diseases

Cells in our body are constantly engaged in physical interactions. They stick together, squeeze through each other, and each possesses a primitive sense of touch. These physical interactions are crucial in processes that control how we grew from a single cell into a complex organism and how they function. In diseases from cancer to neurodegeneration to chronic inflammation, these mechanical regulatory mechanisms are interrupted or impaired, causing cells to lose control and wreak havoc in our body.

The research proposed here aims to understand the changes to mechanical interactions in diseases down to the molecular scale. To do so, we need to develop tiny molecular tools that will allow us to look at these mechanical interactions through a microscope and control them with drugs.

We will build these tools using the latest DNA nanotechnology, which gives us predictable control over the shape and function of these molecules. We will apply these tools to understand how cancer metastasize to a new place in the body and how neurons break connections in neurodegeneration. This will help us identify drug targets towards a cure to two major diseases with high impact to the health of people in our society.

Advancing Health Equity Action

The trajectories of people's lives are often shaped by things that fall outside of their control, having more to do with unearned disadvantages than with their own behaviours or biology. Despite solid evidence and practical policy solutions, systematic differences in health and health outcomes persist both within and between countries. Evidence shows the distribution of power, resources, and wealth along social gradients are causes of these inequities. Many people working in health and health research, and particularly in public and global health, describe their work as reducing health inequities or advancing health equity; but research shows their efforts are often poorly aligned the evidence, focusing on symptoms and not causes. 

This program of knowledge translation science supports researchers, students, and professionals in different settings (e.g., rural communities, municipalities, health systems) to align their equity intentions with evidence about causes of health inequities. By supporting people to integrate evidence-informed strategies and principles, efforts to improve population health can move toward more productive health equity action that focuses on addressing the causes, rather than symptoms, of inequities.

Novel bioengineered probiotics increase colonization and persistence in the gut enhancing bioavailability and their therapeutic potential for inflammatory bowel disease

Inflammatory bowel disease (IBD) is a major global health burden and the rapid surge in pediatric cases in Canada over the past decade is raising alarm bells. Current pharmaceutical therapies are risky or ineffective, cost and health-wise, especially for long-term use and are associated with severe side effects. Therefore, new alternative therapies for IBD are needed urgently. Probiotic therapy, which is the ingestion of non-pathogenic microorganisms to provide health benefits, is considered a potential treatment option. However, clinical trials using probiotics for IBD treatment have yielded very inconsistent and difficult to interpret data.

Specific to IBD, the gut environment is highly inflamed and oxidized; these properties may interfere with the growth and therefore beneficial effects of probiotics. As such, current probiotics are ineffective at persisting in the hostile gut of IBD patients. A novel therapeutic approach is to engineer designer probiotics that strategically target these limitations. The present invention relates to bioavailable and optimized genetically-engineered recombinant probiotic bacteria with enhanced therapeutic potential, for use in treating IBD.

Here we propose that our novel patented next generation microtechnology is an alternative to traditional probiotics to enhance bioavailability and is a potential alternative therapeutic option for IBD. This proposal aims to test how the designer probiotics enrich gut health in pre-clinical

Impact of Hypertension on Lung-Heart Interaction in Patients with Chronic Obstructive Pulmonary Disease

Over 2.5 million Canadians have chronic obstructive pulmonary disease (COPD), which is a progressive lung condition that blocks the airways and makes it difficult to breathe. These patients experience worsening shortness of breath, increasing exercise limitation, and reduced quality of life. Patients must work harder to breathe, and the lungs can over-inflate, which can squeeze the heart and affect how it functions. Further, more than 1-in-4 patients also have high blood pressure, which might amplify the negative effects of lung over-inflation on the heart. This is important because cardiovascular issues contribute to exercise limitation and account for 25% of deaths in COPD.

This study will use non-invasive imaging and monitoring to measure heart function and blood pressure. First, to understand the direct effects of lung volume and blood pressure on the heart, we will study how lung over-inflation can affect heart function when blood pressure is normal or high in healthy adults by using temporary experimental increases in lung volume and blood pressure. Second, we will perform a similar study in patients with COPD, which will allow us to better understand why patients who have COPD are more affected by cardiovascular disease.