Innovation and Translational Research Awards 2024 Recipients

Taking innovative research from concept to application is critical for improving health care systems and the health and well-being of patients. Vancouver Coastal Health Research Institute (VCHRI) is proud to support investigators and their groundbreaking health research with the Innovation and Translational Research Awards. This year’s recipients are putting new knowledge into practice, implementing research outcomes and turning discoveries into commercial opportunities.

The 2024 Innovation and Translational Research Award recipients are:

• Dr. Peter Black, uro-oncologic surgeon and professor in the Department of Urologic Sciences at UBC
• Dr. Naisan Garraway, trauma surgeon and clinical associate professor in the Department of Surgery at UBC
• Dr. Emilie Joos, trauma surgeon and clinical associate professor in the Department of Surgery at UBC
• Dr. Dirk Lange, associate professor in the Department of Urological Sciences at UBC
• Dr. Julia Naso, pathologist and clinical assistant professor in the Department of Pathology and Laboratory Medicine at UBC
• Dr. Dena Shahriari, assistant professor in the Department of Orthopaedics and School of Biomedical Engineering at UBC
• Dr. Karen Sherwood, director of the Vancouver General Hospital (VGH) Immunology Laboratory and clinical assistant professor in the Department of Pathology and Laboratory Medicine at UBC
• Dr. Brian Grunau, emergency physician and assistant professor in the Department of Emergency Medicine at UBC 

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Improving cancer screening in lynch syndrome using urine tumour DNA

Lynch syndrome (LS) is a common cause of hereditary cancer. The condition is associated with a change in the DNA sequence in mismatch repair (MMR) genes. Urothelial cancers of the bladder and urinary tract are the third most common cancer after colorectal and endometrial cancers in individuals with LS, with one in four lifetime risk of developing urothelial cancer.

While LS-related cancers are curable, early detection is crucial to increase the chances of successful treatment outcomes. Black’s clinical trial, which is spearheaded by his post-doctoral fellow Jussi Nikkola, will use novel urine tumour DNA (utDNA) technology to identify emerging asymptomatic urothelial cancers in LS patients, with the goal to demonstrate that a urine-based liquid biopsy protocol is a practical, cost-effective and non-invasive tool to improve cancer screening in LS. The project also aims to improve the understanding of early-stage urothelial cancers in LS and to strengthen utDNA-based cancer detection in other patient groups, ultimately to reduce disease advancement and the essential employment of invasive and expensive testing methods. 

“Adopting cutting-edge technologies like next generation sequencing of utDNA is essential to improve cancer detection and promote precision cancer care in B.C.,” says Black. 

New risk stratification tool for earlier recognition of traumatic hemorrhage

The most common cause of preventable mortality in trauma patients is uncontrolled bleeding. Up to 16 per cent of hemorrhagic deaths result from delays in recognition and intervention. The CAN-BLEED score is a novel clinical risk stratification tool that estimates the risk of major bleeding for trauma patients. 

Dr. Garraway’s study aims to validate the current CAN-BLEED score and compare its performance to existing risk stratification tools for bleeding assessment. Data will be collected from patients aged 16 years and older who arrive at VGH within three hours of trauma to the thorax, abdomen or pelvis, and who require trauma team activation. Data collected will include major interventions initiated, number of blood transfusions received, need for intensive care unit (ICU) admission, in-hospital mortality, 30-day mortality and hospital and ICU length of stay.

“The validation of a refined CAN-BLEED score and improvement over the existing scores is an important step toward nationwide efforts to make a practice-changing impact,” says Garraway. “Using this tool for earlier recognition of uncontrolled bleeding could lead to major decreases in mortality and hospital length of stay for trauma patients at VGH.”

Reducing venous thromboembolism complications through precision medicine

Around six per cent of patients admitted to VGH for a major trauma develop a venous thromboembolism (VTE) — a blood clotting condition associated with increased complications and death. If discovered early, VTE is preventable and treatable. However, perceived risks for clotting and bleeding vary for each patient, which makes decisions such as timing and dosing of anticoagulation medication challenging. 

In a previous meta-analysis, Joos found that using serum anti-Xa targets — a specific type clotting factor — to guide appropriate anticoagulation dosing, may be more effective than standard fixed dosing for VTE prevention. The goal of this randomized controlled trial is to evaluate the identification and recruitment of eligible trauma patients, as well as evaluate adherence with anti-Xa guided anticoagulation dosing, which will ultimately inform and support a larger study. 

“Our project will serve as a feasibility study for a larger research program that aims to reduce VTE complications and aid in clinical decision-making,” says Joos. “An improved strategy for pharmacologic VTE prevention will directly impact patient health at VGH and globally, resulting in significant reductions in patient morbidity and mortality.”

Using a silver-based antibacterial coating technology to prevent catheter-associated urinary tract infections

Current treatment strategies for preventing catheter-associated urinary tract infections (CAUTIs) include antibiotics and novel catheter materials. However, these often result in poor outcomes due to challenges, such as the development of antibiotic-resistant bacteria and the reliance on contact killing which results in the accumulation of dead bacteria on the device surface.

To address this urgent clinical need, Lange and collaborator Kizhakkedathu developed a novel substrate-independent covalent antibiofilm coating technology called Silver-based Antibacterial Film-forming Engineered coating (SAFEcoat). This is the only coating technology to combine both anti-adhesive and sustained silver releasing mechanisms, keeping the catheter surface clean, allowing for long-term release of antimicrobial silver to kill bacteria repelled into patients’ urine. 

The novel catheter technology may be able to treat a pre-existing infection and maintain a sterile environment to prevent hospitalization due to serious infections. Based on preclinical results demonstrating the safety and superior activity of SAFEcoat to prevent implantable-device infections, the research team’s next step is to assess SAFEcoat’s clinical efficacy and compare it to existing antimicrobial catheters, focusing on individuals living with spinal cord injury. 

“SAFEcoat has shown great potential to reduce one of the leading causes of health care-associated infections, which come with a significant burden to the health care system in terms of resource use and allocation,” says Lange. 

Identifying the origin of tumours to improve cancer diagnostics

Distinguishing between primary and metastatic squamous cell carcinomas is critical for treatment decisions. While new primary tumours still localized to their sit- of-origin may potentially be cured through removal, metastatic tumours that have spread from other sites may require more widespread systemic treatment. However, it can be impossible to determine a tumour’s site-of-origin with conventional approaches.

Naso aims to develop methods to distinguish primary and metastatic squamous cell carcinomas and determine their site-of-origin. This research includes: developing a shallow whole genome sequencing (sWGS) workflow, developing a methylation-based classifier for squamous cell carcinoma site-of-origin and determining classifier performance when applied to nanopore sequencing data. Findings from the study will form the foundation for the clinical implementation of sWGS. 

The proposed methylation classifier would provide the first comprehensive and accessible classifier for squamous cell carcinomas of unknown origin. Nanopore sequencing has never been clinically implemented for carcinoma tumour tissue for site-of-origin determination, but has the potential to provide critical diagnostic information in a clinically relevant timeframe. 

“We are focused on cost-effective and rapid testing methodologies that could be applied clinically, and are planning to offer global open access to the classifier,” says Naso. “Pioneering these approaches could leverage the promise of genomic and methylomic profiling across cancer diagnostics.”

Regenerative interfaces for enhanced upper limb prosthetics

While lower limb prosthetics usually improve a person's quality of life, individuals with upper limb amputations may prefer to not wear a prosthetic. Patient decision-making can be due to the impracticality of some prosthetics given the substantially greater number of motions made by upper limbs compared to lower limbs. In addition, the prosthetics cannot impart tactile and proprioceptive sensations to the user. Instead, patients must rely on visual cues to be aware of prosthetic limb location in relation to their surroundings.

Previous prosthetics research has involved the use of wearable sensors or implantable electrodes as an interface between prosthetics and patients’ muscles or nerves. While encouraging progress has been made, major roadblocks remain in place, including a lack of communication between devices and the different types of motor and sensory neurons within a person’s nerve. Shahriari’s study is developing a neural interface that enables relaying information from the cross-section of a person’s nerve, thus enabling a wider range of neural input and output via neural recording and electrical stimulation. 

"If successful, our study will introduce a technology that can eventually provide a bi-directional communication between a prosthesis and its user, potentially transforming the utility and efficacy of upper as well as lower limb prosthetics,” says Shahriari. 

Using single antigen beads to detect HLA-specific cells for improved transplant outcomes

While transplant survival has greatly improved in recent years, acute and chronic rejection remains a major cause of graft loss. Alloimmune T cells are the main driver of these rejections, resulting in increased efforts to identify these cells. Although several commercial products have been developed to screen donor serum for donor-specific antibodies, no such investigative procedure is currently available to identify donor-specific T cells. 

Sherwood’s study will repurpose an existing assay — a way of indexing underlying health markers within cells — for human leukocyte antigen (HLA) antibody screening to detect HLA-specific T cells using single antigen beads. If successful, the assay could be moved into a clinical setting to help reduce the incidences of rejection by decreasing the number of potentially dangerous patient-donor pairings, as well as through more precise monitoring of the reproduction of alloreactive T cell clones. 

“Making this assay readily available to transplant patients would provide an inexpensive and easy-to-use platform for immunophenotyping alloreactive T cells,” says Sherwood. “Additionally, the proposed assay would enhance our understanding of alloimmunity in general."

A novel biosensing wearable device for improved detection of sudden cardiac arrest

Approximately 36,000 Canadians experience an unexpected sudden cardiac arrest (SCA) each year, resulting in nearly 100 preventable deaths every day. These events require rapid access to professional intervention, as the chances of survival without brain damage decrease with each passing minute until paramedic arrival. Unfortunately, 75 per cent of SCAs occur when an individual is alone or asleep, with no one there to call 9-1-1.

Immediate recognition is the single greatest means of improving SCA survival. Grunau’s project will develop a wrist-wearable sensor that can accurately detect SCA and alert emergency service providers of a cardiac event. While commercial wearable sensors, such as smart watches, are currently available, they are only designed to assess normal physiological values and cannot identify when vital signs are missing. 

The research team will specifically examine the benefits of near infrared spectroscopy (NIRS), over traditional pulse oximetry, in identifying cardiac arrest with sensors placed at the wrist. As opposed to oximetry technology, NIRS sensors are not currently found in smart watches. Using data collected from current testing protocols, the team will use machine learning algorithms to accurately identify SCA.

“By developing NIRS-based biosensing wearable technology with a cloud-based, secure computing system, the device can continuously monitor sensor signals and make decisions on alerting 9-1-1,” says Grunau. “This could lead to an estimated 450 additional SCA survivors in B.C. annually.”