Research Location: St Paul's Hospital

Exercise therapy to reverse sepsis-induced immune suppression

Sepsis is a serious and life-threatening condition that arises from infections. Although medical advances have reduced the mortality rates of sepsis, many survivors have a weakened immune system and are at a higher risk for subsequent infections. Exercise represents a powerful tool to recover the immune system and reduce post-sepsis hospitalization. Through my research, I will explore how exercise impacts the immune system of sepsis survivors by specifically investigating immune cells called myeloid cells, which become dysfunctional following sepsis. Initial results in a mouse model of sepsis have found that four weeks of exercise improves survival to a subsequent lung infection due, in part, to restoration of immune system function and that female mice respond differently to sepsis than male mice. To understand this better, I will investigate how exercise changes immune cells and differences between sexes. In collaboration with an ongoing clinical trial in sepsis survivors, I will explore whether molecular changes in immune cells are present in human patients. Overall, my proposed research will lead to more effective exercise treatments for sepsis survivors to improve their quality of life and return back to health.

Clinical Genomics for Enhanced Infectious Disease Diagnosis

This research will use advanced DNA sequencing techniques to enhance the way we diagnose and treat infectious diseases. In many serious infections, the cause cannot be identified, and the patient must be treated with broad-spectrum antimicrobials, which can either kill the pathogen and harm the microbiome, or even fail and promote resistance. We will use a novel technique, metagenomic sequencing, to analyze patient samples and identify the exact cause of the infection, including those caused by rare and unknown microorganisms. DNA sequencing will also be used to study these microorganisms in real time and determine the genetic mechanisms by which they cause disease and develop resistance to antimicrobial drugs. Armed with the genetic information of these microorganisms, we will also be able to create new, rapid tests to quickly identify them in patient samples. This research will improve patient care by enabling faster and more accurate diagnosis of infectious diseases, leading to better treatment outcomes and potentially reducing the spread of antimicrobial resistance.

Integrating Genetics Care in Nephrology to Study and Empower Precision Medicine

One in ten Canadians have kidney disease which can ultimately require treatment with dialysis or kidney transplant or lead to death. Treatment of kidney disease depends on us understanding its cause. Genetic causes of kidney disease, due to changes in people’s genes or DNA, are increasingly recognized as important causes of adult and childhood disease. We do not know how many people in British Columbia have genetic kidney diseases or their impacts on health.
One in eight people with kidney disease do not have a clear explanation for the cause of their kidney disease, termed unexplained kidney disease. We think there are unidentified genetic changes that explain some of these peoples’ kidney disease.
We will look at how many people in British Columbia have genetic kidney diseases based on clinical genetic testing and how genetic kidney diseases impact their health . This will include a few pre-specified groups of people with common genetic conditions. We will then perform whole genome sequencing on people with unexplained kidney disease to try to find new genetic changes that explain why they have developed kidney disease. We expect these findings to improve the health of people living with kidney disease in British Columbia.

The effects of dietary nitrate supplementation on exercise tolerance in patients with fibrotic interstitial lung disease

Health Research BC is contributing matching funds to support the CANTRAIN-CTTP & Michael Smith Health Research BC Doctoral Studentship 2023 Award Program. Olivia Ferguson is a Ph.D. student at the University of British Columbia. Olivia will be conducting a clinical trial in patients with chronic lung conditions under the supervision of Dr. Jordan Guenette at the Cardiopulmonary Exercise Physiology Laboratory at St. Paul’s Hospital in Vancouver, BC.  

 

Interstitial lung disease (ILD) is a chronic progressive lung disease of either known or unknown cause, with a mean survival of only three years. ILD leads to progressive scarring of the lungs and debilitating reductions of exercise tolerance and functional abilities, which is strongly associated with reduced quality of life and mortality. Breathlessness and severely low oxygen levels in the blood are the hallmark features of ILD, which worsen with exercise. Unfortunately, very few effective and safe pharmacological therapies that target the lungs are available for ILD. Thus, preserving or enhancing muscle and heart function is essential to offset the progressive decline in lung health and for maintaining quality of life and independence. It is strongly advised that individuals with ILD undergo pulmonary rehabilitation, which is a structured exercise program; however, this may not be suitable for individuals who may not be able to handle strenuous exercise that can enhance muscle and heart function. Using nitrate in the form of concentrated beetroot juice, a safe and commercially available dietary supplement, may improve the delivery and efficiency of oxygen use at the site of exercising muscles. Orally ingesting dietary nitrate may improve the use of diminished oxygen availability rather than relying on external sources of supplemental oxygen, a common practice in ILD, which lacks real-world practicality. This novel therapeutic may allow individuals with ILD to reach exercise intensities sufficient for improving their overall exercise tolerance. If successful, it would enable them to sustain their functional abilities and engage in regular daily tasks, promoting independence and improved quality of life.

Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE)

Health Research BC is providing match funds for the Master’s Studentship 2023 Award, supported by the Canadian Consortium of Clinical Trial Training Platform (CANTRAIN). As part of my work, I will be conducting the Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE) study. The ACCURATE, BC-based study is also funded by Genome British Columbia and Vancouver Coastal Health Research Institute (VCHRI).  

Familial hypercholesterolemia (FH) is one of the most common genetic diseases, affecting 1 in 250 individuals and elevating the risk of early onset heart disease. About 1 in 14 individuals who have a heart attack under 60 years old have FH, but 99% of them were not aware of it before their heart attack. In British Columbia, over 85% of individuals with FH remain undiagnosed due to the lack of genetic testing, leading to missed opportunities for early intervention.  

The ACCURATE study aims to investigate how genetic testing for patients hospitalized with acute coronary syndrome (ACS) can improve the diagnosis of FH, influence physicians’ treatment approaches, patients’ medication use, and ultimately reduce the disease burden for these patients.  

The outcomes will contribute to understanding how genetic diagnosis influences patient care in acute cardiac settings, with the hope of influencing healthcare practices in the entire province. This will improve the health of British Columbians and enhance the reputation of BC as a leader in genomic clinical care. 

 

 

End of Award Update – December 2024

 

Results

The ACCURATE study found that 8% of young acute coronary syndrome (ACS) patients with untreated LDL-C >4 mmol/L had a genetic diagnosis of Familial Hypercholesterolemia (FH). This is a prevalence 24 times higher than in the general population. Importantly, genetic testing reclassified 88% of these patients initially categorized as “unlikely” or “possible” FH to a confirmed diagnosis of “definite” FH. These findings show that genetic testing can identify FH in patients who would otherwise be missed using traditional clinical criteria alone. Additionally, 24% of patients were identified as having polygenic hypercholesterolemia. These patients did not carry variants in the known FH-causing genes but had a high LDL polygenic risk score (PRS), indicating that other genetic factors contribute to their elevated cholesterol and heart disease risk. Altogether, our current results highlight the value of both genetic testing and polygenic risk scoring in detecting, diagnosing and understanding FH in young high-risk patient populations.  

 

Impact

The ACCURATE study has addressed a significant gap in care by diagnosing FH-positive patients in an acute cardiac care setting where genetic testing is not currently performed and therefore, these patients would likely remain undiagnosed. By providing treating physicians with genetic test results within 1 month of their patients’ ACS event, this study has raised awareness of the genetic basis underlying their patients’ premature cardiovascular events. While it is too early to measure changes in long-term outcomes, this approach ensures physicians are better informed to consider these insights in real-time clinical decision making and follow-up care. The rationale for conducting this research and the early results from ACCURATE has also inspired conversations with policy makers, industry experts, and healthcare providers in BC about the importance of integrating clinical FH genetic testing in the province. 

 

Potential Influence 

This study has the potential to change the standard of care for young patients with heart attacks by making FH genetic testing routine, especially for those with high LDL levels. This would lead to earlier detection of FH and may also highlight the importance of tailoring treatment intensity based on genetic findings, thus allowing physicians to identify those who may require more aggressive interventions to achieve lipid targets and prevent further cardiovascular events. Over time, this approach could help lower the rates of heart attacks and other cardiovascular events caused by undiagnosed or undertreated FH in British Columbia. Beyond its local impact, the study may provide a clear model for integrating genetic testing into acute cardiac care that can be adopted nationally and internationally.  

 

Next Steps

ACCURATE is ongoing as patients in the Active Testing Phase are still being followed to assess outcomes including treatment intensification, lowest LDL-C achieved, guideline lipid target attainment at 15-months post ACS, and the rate of recurrent cardiovascular events. Next steps include assessing how these genetic results for FH impact physicians and their patients, particularly how they are integrated into clinical care. For this reason, we plan to conduct a survey to explore physicians’ reactions to and concerns regarding FH genetic results, assess the influence on clinical workflow, changes in treatment plans, and identify ways to support physicians in better diagnosing FH and delivering optimal care for patients. Additionally, exploring genetic testing for first-degree relatives may be a future direction to help identify more individuals with FH, therefore extending the reach and impact of the study.  

Investigating psychomotor response to L-DOPA challenge as a biomarker for clinical outcomes in late-life depression: A pilot feasibility trial

Major depressive disorder (depression) is a common condition affecting older adults, also called late-life depression (LLD). Depression later in life can negatively impact overall health, including increasing the risk of developing dementia. With Canada’s aging population, it is important to develop more effective ways of managing this condition.  

 

LLD is frequently associated with a phenomenon called psychomotor slowing, which is a decrease in the speed of both physical movements and information processing. The presence of psychomotor slowing can signify more severe illness and a risk of worse outcomes in LLD. Psychomotor slowing in LLD is related to the abnormal functioning of dopamine, a neurotransmitter that influences motivation, reward, and pleasure in the brain. This slowing may be reversible by taking a dopamine-like medication called levodopa (L-DOPA). However, we do not know whether there is a link between psychomotor slowing, reversibility by L-DOPA, and treatment outcomes in LLD. 

 

I am a geriatric psychiatrist at St. Paul’s Hospital and a postdoctoral research fellow at the University of British Columbia. My study, which is supported by the CANTRAIN-CTTP & Michael Smith Health Research BC Post-Doctoral Studentship Award and conducted at St. Paul’s Hospital in Vancouver BC, will invite participants to receive two weeks of treatment with a drug called Levocarb which contains L-DOPA (an L-DOPA “challenge”). We will measure participants’ walking speed, overall speed of movements, and cognitive function before and after the challenge.  

 

The goal of this study is to evaluate whether psychomotor slowing in LLD changes in response to changes in brain dopamine levels, and whether this change can predict improvements in depression symptoms and cognitive function following standardized antidepressant treatment. These data will improve our understanding of the biology of LLD and may enhance our ability to predict which treatments will be most helpful for older adults suffering from depression. 

 

 

End of Award Update – February 2025

 

Results

My pilot clinical trial has provided some of the first-ever data on the psychiatric, psychomotor, and cognitive effects of levodopa (L-DOPA) in depressed older adults. So far, we are observing significant improvements in psychomotor speed, working memory, and depressive symptoms in response to a 2-week administration of L-DOPA. 

 

Impact

This clinical trial has provided, to my knowledge, the first BC-based opportunity to participate in clinical interventional research for older adults living with depression. This research is providing access to a novel treatment approach which will benefit health outcomes for older adults in BC and, possibly in the future, the rest of Canada and beyond. 

 

Potential Influence

This clinical trial is the first in a planned sequence of studies to investigate the usefulness of L-DOPA as a challenge medication to help predict response to other medications in late-life depression. If successful, this research will lead to a practical clinical tool that enables us to provide personalized, evidence-based treatment options for older adults with depression. 

 

Next Steps

Early results from this study are being prepared for publication and will be presented at upcoming conferences. A follow-on study with a randomized component is currently being planned, which will build off our promising pilot data. 

Bridging the gap: screening for fontan associated liver disease (FALD)

One in 3,000 children is born with one, instead of two, heart pumps, and as a result of a surgery called the “Fontan”, survive well into into adulthood. This surgery creates an artificial path that collects blood low in oxygen from the veins and sends to the lungs (instead of using a right heart pump) to pick up oxygen; leaving the single pump to send blood with oxygen to the body. We are learning these patients are developing many issues in adulthood including liver disease. The best way of identifying significant liver disease is through a liver biopsy, but it is not reasonable to perform biopsies regularly. We do not know the best way to easily identify and monitor liver disease in the Fontan population, yet this knowledge is critical to maintaining Fontan liver health, reducing co-morbidities ultimately benefiting our health care system. The first part of the study will be undertaken at St.Paul’s Hospital and Mazankowski Heart Center in Edmonton. We will perform a number of liver related blood tests/imaging to determine the best combination that identifies significant liver disease as diagnosed by liver biopsy. The second part will take place at five adult sites across Canada and will confirm our findings from the first part.

Familial hypercholesterolemia patient engagement forum: Family care and women’s health

Familial Hypercholesterolemia (FH) is the most common inherited disorder, with a prevalence of 1 in 250 Canadians, characterized by lifelong elevation in blood cholesterol leading up to 22-fold increased risk for heart disease. Despite this, in BC alone, more than 85 percent of cases are undiagnosed and only a minority receive appropriate treatment. A key component for improving care for this population is by increasing awareness through patient education, engagement and dissemination of recent FH research results. The purpose of this proposal is to organize an updated educational forum on FH, focusing specifically on family-based care and women’s health, including lectures by patients, physicians, dietitians and genetic counsellors, and interactive group sessions including patients’ testimonials. This forum will provide an opportunity for patients to learn about new developments in diagnosis and treatment of FH, including management in special populations, such as pregnant women and children. The goal is to empower patients to become advocates for the FH community by increasing awareness of the disease and recognizing the importance of screening their families for early identification, treatment and ultimately heart disease reduction.

Team members: Iulia Iatan (UBC, Centre for Heart and Lung Innovation); Nancy Pratt-Najera (St. Paul’s Hospital); Lubomira Cermakova (St. Paul’s Hospital, Healthy Heart Program Prevention Clinic); Durhane Wong-Rieger (Canadian Organization for Rare Diseases).

Determination of the optimal SARS-CoV-2 vaccination strategy to achieve a robust and long-lasting immune response

Global COVID-19 vaccine distribution has been inequitable, with high-income countries afforded widespread access to vaccines and boosters, while among the low-income countries only 2 percent of individuals are vaccinated. Consequently, over 50 percent of the world’s population remains unvaccinated. Fortunately, however, data from vaccinated cohorts can inform the most efficient and effective community-level vaccination strategies for the unvaccinated populations. Currently approved mRNA vaccines were initially tested with dosing intervals of 21-28 days; however, this may lead to suboptimal immunity. Further, data informing the optimal timing and frequency of booster doses is lacking. This project will answer critical questions regarding the optimal vaccination strategies to achieve a robust long-lasting immune response. In this study I will employ data from a prospective national cohort of adult paramedics, providing sociodemographic data and serum blood samples. I will identify the optimal vaccination strategies to achieving a robust immune response at 12, 18 and 24 months, including examining differences between sex, race, and age. These data will inform ongoing global vaccination efforts, to maximize efficiency and long-term protection.

End of Award Report – June 2025

 

Results

My project led to several important findings that have helped improve how we understand and manage COVID-19, especially for frontline workers like paramedics. One major result was showing how immunity from COVID-19 vaccines can decrease over time. This helped inform decisions on when people should get booster doses to stay protected—an issue that was especially important for high-risk groups in British Columbia.

We also found that bivalent booster vaccines—which target both the original virus and newer variants—produced stronger immune responses than earlier vaccines. This helped guide vaccine policies and gave reassurance that updated vaccines were working better for people on the front lines. Another exciting part of the research was studying how many vaccines people had and how that affected their immunity against newer variants like Omicron. We also looked into a theory called antibody imprinting to understand how previous exposure to the virus or vaccines might shape future immune responses. These findings offered new insights into how the immune system remembers and reacts to COVID-19.

In addition, we explored the link between COVID-19 infections and long-term symptoms among vaccinated paramedics. This helped raise awareness of post-COVID or “long COVID” issues, even among people who had been vaccinated. My work didn’t just stay in academic journals—it was shared with public health officials and helped improve how COVID-19 is managed among paramedics and other healthcare workers in BC and across Canada. The results also have broader value for similar workers across North America.

 

 

Impact

The research supported by my partnered award has already made a meaningful impact on public health in British Columbia and beyond. Our findings have helped guide decisions about when booster COVID-19 vaccines should be given and provided evidence supporting the use of bivalent booster vaccines to strengthen protection, especially among frontline healthcare workers like paramedics.

My work has also raised awareness of long COVID symptoms among vaccinated individuals and contributed to improving occupational health policies for high-risk professionals. Public health officials and healthcare leaders have used our findings to shape vaccine rollout strategies, protect essential workers, and reduce COVID-related risks in real-world settings.

In addition, the project has led to the publication of 10 peer-reviewed studies, which are already being cited by researchers and health agencies, showing that our work is contributing to both scientific knowledge and real-world decision-making.

 

Potential Influence

The research supported by my partnered award has strong potential to continue influencing vaccine policy, occupational health practices, and pandemic preparedness. As COVID-19 evolves and new variants emerge, the evidence we’ve generated on vaccine durability, booster timing, and immune response patterns will help shape ongoing vaccination strategies and booster recommendations for high-risk populations across Canada and internationally.

Beyond COVID-19, our research framework—particularly our approach to studying immune responses in real-world frontline settings—can serve as a model for evaluating vaccines in future outbreaks or public health emergencies. The methodologies and partnerships developed through this award also lay the foundation for new collaborative research that could expand into other areas of infectious disease control and immunization science. Ultimately, this work will continue to guide decision-makers in protecting essential workers, refining immunization schedules, and adapting public health interventions to emerging challenges.

 

Next Steps

I will be focusing on further research on Long COVID (post COVID condition) burden among paramedics in Canada. Will also try to compare the burden of Long COVID among several essential healthcare workers in Canada

Translating research into practice: Investigating the impact of Alzheimer’s disease diagnostics in Canada (IMPACT-AD)

Health Research BC is providing match funds for this research project, which is funded by the Brain Canada Multi-Investigator Research Initiative (MIRI) – Improving Health Outcomes and Quality of Life. Additional support is provided by UBC Faculty of Medicine, Djavad Mowafaghian Centre for Brain Health, and Women’s Brain Health Initiative. The research is also being undertaken in collaboration with the Canadian Consortium on Neurodegeneration in Aging.

 

Early and accurate diagnosis of Alzheimer’s disease is critical as timely access to health care and community services has the potential to slow disease progression and improve quality of life. Current approaches for diagnosis rely on traditional imaging tests and observation of the signs and symptoms of the disease. Adding the measure of proteins found in cerebrospinal fluid (biomarkers) has been shown to help correctly identify the disease and predict those with mild symptoms that are likely to progress to dementia; however, such testing is not readily available in Canada.

 

The IMPACT-AD study specifically addresses barriers to uptake and use of Alzheimer’s disease biomarker testing in the Canadian health care system. This Canada-wide study will develop a comprehensive understanding of how biomarkers for Alzheimer’s disease impact clinical decision making and health care costs. Collaborating with patients, caregivers, and physicians, IMPACT-AD will also investigate the effect of testing on personal decision-making. The findings of this study will lay the necessary groundwork, modernize, and improve the care available to Canadians affected by Alzheimer’s disease and related forms of dementia.

 

IMPACT-AD is led by Dr. Mari DeMarco, a clinical chemist at St. Paul’s Hospital, and a clinical associate professor in Pathology and Laboratory Medicine at UBC. DeMarco is joined by a multidisciplinary team that includes both Canadian and international laboratory medicine specialists, geriatricians, neurologists, health economists, rural/remote clinicians, ethicists, and statisticians.

 

For more information about the study and how you can get involved, visit www.impactAD.org.

Award update: December 2021