Advanced multi-functional in vivo retinal imaging for ocular oncology

Ophthalmic imaging plays a crucial role in the evaluation, follow-up, and treatment decision-making in ocular oncology. This critical role is even more prominent when dealing with the early-stage choroidal melanoma or amelanotic tumor patients, in which diagnostic uncertainty is especially prevalent. This is due to the significant overlap in the clinical and imaging findings of benign and malignant choroidal tumors. Current imaging modalities are not helpful in reliably differentiating the malignant features in suspicious choroidal lesions and often require long-term serial follow-up that places a significant burden on patients and providers. Recent studies have shown that melanin alternation in the choroid is correlated to the malignancy and metastasis potential in choroidal tumor patients. The main goal of my research is to develop a novel high-resolution, molecular-specific clinical ophthalmic imaging system to visualize and quantify the melanin contents in choroidal tumor. This research outcome will provide important diagnostic clues in the evaluation of choroidal tumors, facilitating early non-invasive identification of high-risk features of malignancy.

Improving genomic epidemiology methodologies and practice through interdisciplinary data integration and analysis

Infectious diseases as shown by the COVID-19 pandemic, remains a serious threat. Genomic sequencing has revolutionized the detection and characterization of pathogens for surveillance and outbreak investigation, creating the new field of genomic epidemiology. During this ongoing pandemic, we have witnessed several gaps in establishing effective global responses that require coordinated action such as our ability to quickly adapt analytical methods to new pathogens and the ability to integrate several data sources to generate knowledge for enabling evidence-informed decision making. In this proposed research, I aim to further this field of genomic epidemiology by developing advanced data analysis methods. Additionally, I aim to optimize these methods to be capable of adapting to datasets from various pathogens, saving time to develop again for every outbreak. Finally, I want to combine genomics and advanced data analysis (bioinformatics) to establish a method of integrating epidemiological, political, and other contextual information with genomic data to improve public health preventive measures. This project will develop a program to use intersectoral genomic epidemiology for countering infectious diseases.

Molecular determinants of pathogenesis and clinical outcomes in high-grade B-cell lymphoma

One-third of patients with aggressive non-Hodgkin lymphoma relapse after conventional chemotherapy and die of their disease. We need new methods to identify, at diagnosis, which patients have a high risk of relapse to improve their treatment. Genetic profiling is a powerful tool that can identify these high-risk patients. ‘Double-hit lymphoma’ (DHL) is one type of lymphoma that responds poorly to standard treatment. Current testing strategies cannot accurately identify all patients with DHL. We aim to improve the identification and treatment of DHL with a new test that uses a unique ‘genetic blueprint’. We will apply this test on lymphoma samples from 900 aggressive lymphoma patients in British Columbia to find out its ability to identify DHL patients compared to current methods. Patients who carry this genetic blueprint may benefit from different treatment approaches that overcome the high risk of relapse. We will also conduct an in-depth genetic analysis of DHL to understand how these lymphomas develop in the body. This new knowledge will help design smarter therapies that target the tumour while sparing normal body cells. These ‘targeted therapies’ can avoid the significant side effects caused by intensive chemotherapy.

Smart Discharges for Mom+Baby: Saving mother-newborn dyads by developing a predictive risk model to identify vulnerable dyads and guide delivery of post-discharge care

The risk of a mother or baby dying is highest in the first six weeks after birth. The World Health Organization (WHO) recommends regular follow-up visits for all mothers and their newborns. This is not always possible. In resource-constrained countries, a lack of money and nurses at hospitals and limited time and money at home often stops mothers from seeking care. In our study, we will build a score to identify mother-baby pairs that are most at risk of getting sick or dying in Uganda. The health of a mother impacts the health of their baby, and vice versa. Our risk score combines the risk of the mother and baby so that both can get care when they need it. A nurse can use this score to guide the number of follow-up visits recommended for the pair. In this way, mothers and babies at higher risk receive more visits. We will also talk to parents and nurses to determine what stops mothers and babies from receiving a follow-up visit. We will work with our Ugandan partners to remove these barriers so that improvements in care are long-lasting. In the future, we can use this approach to improve the health of mothers and babies in smaller, remote towns in BC, where specialized care for mothers and babies is not always readily available.

Innate immune mechanisms of viral myocarditis: Role of the cytosolic DNA-sensing pathway

Coxsackie virus B (CVB) is the number one cause of viral heart inflammation leading to heart failure and sudden death in ~20 percent of infected children and young adults. In most people, CVB infection causes mild symptoms. However, individuals with underdeveloped and/or compromised immune systems are at increased risk of severe disease. Normally, our healthy immune system acts as a first line of defense against viruses, but excessive and sustained activation of our immune system can be harmful, leading to chronic inflammation and injuries to the heart. The objective of my project is to study how CVB hijacks a novel immune pathway called cGAS-STING, to trigger harmful inflammation in the heart. Our knowledge gap is that we do not completely understand how CVB hijacks the cGAS-STING immune pathway and whether blocking this pathway with drugs can protect the heart. To accomplish this goal, we will precisely identify which cells and immune pathways are responsible for harmful inflammation of the heart. Findings from this study have the potential to open new therapeutic avenues to combat existing and emerging viral threats.

Scaling-up a community-based diabetes prevention program: A longitudinal matrixed multiple case study to examine implementation context

One in three Canadians are affected by diabetes. Diabetes prevention programs can help people considerably lower their risk for Type 2 diabetes. Yet, research understanding how to put programs in place (implement) in community settings is low. Site-specific context is often ignored, limiting program success. This means very few Canadians have access to effective diabetes prevention programs. Small Steps for Big Changes (SSBC) is a program for individuals at risk of developing Type 2 diabetes. This effective program was successfully implemented within two community sites. The program is ready to be implemented across Canada. This project will examine the implementation of SSBC in 10 unique community sites. Each site will be a case study to discover factors that affect implementation. A matrix will organize all the cases to compare results within and between sites. This method will reveal how context impacts implementation (what works, where and why). Results will offer lessons learned on how to successfully implement diabetes prevention programs across different contexts. Ultimately, this project will increase access to an effective diabetes prevention program across Canada.

Transcutaneous spinal cord stimulation for treating neurogenic bladder dysfunction following spinal cord injury

As much as 80 percent of people with a spinal cord injury (SCI) develop urinary bladder problems. Recovery of bladder function is consistently rated as a top treatment priority for people with SCI. Left unmanaged, bladder dysfunction can result in frequent urine leakage or unwanted urine retention that often cause kidney or urinary tract infections which drastically reduce overall quality of life. Despite the prevalence of this issue, treatment for restoring bladder function remains under-emphasized in SCI research. Of even greater concern are consequences associated with rapid, and often life-threatening, increases in blood pressure triggered by bladder care. Electrical spinal cord stimulation via surgically implanted electrodes is a potential treatment option that has been shown to promote functional recovery after SCI by modulating silent spinal circuits. However, the surgical implantation of electrodes and the stimulator is invasive, expensive and has inherent risks. We propose to improve bladder function and prevent associated blood pressure surges via non-invasive spinal cord stimulation using electrodes placed over the skin, thereby minimizing patient risk and obviating the need for invasive and expensive surgery.

Envisioning urban Indigenous-led pathways to mental wellness through community-based research in the interior of British Columbia and new partner engagement in the north

Colonialism, racism, and a lack of culturally safe care result in poorer mental health outcomes for Indigenous peoples in Canada. Indigenous-led services grounded in local values and priorities improve culturally safe care and wholistic health for Indigenous peoples. Urban (off-reserve) Indigenous peoples are, however, often excluded from mental health planning that affects them. This is especially felt by urban Indigenous peoples residing in rural and northern areas. Building on established partnerships with five British Columbia (BC) Interior Friendship/Métis Centres, and Interior Health, this research aims to change this. Together we will: 1) renew/strengthen existing relationships; 2) explore local mental wellness needs and priorities; 3) develop community-led pathways for promoting mental wellness; and 4) engage new community and health system partners in Northern BC. Local Elders, community research liaisons, and advisory teams will direct and facilitate information gathering and sharing. This may include surveys, talking circles, and community gatherings. Results will be community-owned, and shared with directions from communities.

Mechanisms underlying syncope: Defining the role of postural sway and gastric distension, and investigating the possibility of a cerebral trigger

Some people faint often, negatively impacting quality of life. Fainting occurs when the heart cannot pump enough blood to the brain. Standing still pulls blood into the lower body reducing its return to the heart. However, even when standing still, our body sways and these movements may prevent fainting by pushing blood to the heart. Water drinking might also help by stretching the stomach, raising blood pressure. Also, seeing blood/having blood drawn can cause fainting, suggesting the brain may trigger a faint, not the heart. We will examine: i) the role sway plays in fainting, ii) if fizzy water drinking wards off fainting, and iii) brain activity during emotional triggers. Using wearable sensors, we will compare heart rate, blood pressure, and sway patterns in the lab and in soldiers who faint on parade. We will test if drinking fizzy water increases blood pressure more than still water. We will also compare blood pressure, heart rate, and brain activity in fainters and non-fainters while participants watch a video of a blood draw to show the role of the brain in initiating faints. These studies will help us better understand fainting, relieving the healthcare burden and improving quality of life for people who faint.

The role of the innate immune system in hypoxic ischemic brain injury post cardiac arrest

In Canada, more than 50,000 cardiac arrest (i.e. “heart attack”) patients simultaneously suffer from brain injury due to reduced brain blood flow and oxygen delivery. Primary brain injury occurs following the initial reduction in brain blood flow following cardiac arrest, and in some cases, secondary brain injury occurs after brain blood flow is restored to normal levels. However, the physiological mechanism(s) responsible for secondary brain injury following cardiac arrest remain unclear, and the data available in humans are very limited. We hypothesize that a key contributor to secondary brain injury following cardiac arrest is due to consequential activation of the human body’s innate immune system, which signals for excess brain inflammation and results in cellular damage. The proposed investigation, which will be conducted at Vancouver General Hospital, aims to measure key biological markers to quantify brain inflammation in post cardiac arrest patients. The findings from this study will improve our overall understanding of the mechanism(s) that contribute to brain injury characterized by reductions in blood flow and will potentially identify potential therapeutic targets and improve quality of life in these patients.