Program: Match Funding

Development of 3D-printed cardiac organoids for -omics applied to personalized medicine

Our project, made possible with matched funding from Michael Smith Health Research BC, has been funded by Genome Canada’s Canadian Biotechnology Innovation and Commercialization program. This is a BC-based project, in collaboration with Axolotl Biosciences of Victoria. Axolotl is a start-up specializing in producing bioinks for 3D-bioprinting of stem cell-based tissues for applications in disease modeling. In this project, we will develop a bioink meant for stem cell-based heart tissues, to allow us to study heart diseases.

 

In the Laksman lab, we use personalized stem cells to produce heart tissues for in vitro studies. These stem cells are often from individuals with heart rhythm diseases such as atrial fibrillation, and who may have genetic variants of interest. Using our custom-engineered imaging system, we can measure several properties of the heart tissues at the same time – including both electrical and physical properties of the tissue. The ability to 3D-print heart tissues using a novel bioink will increase the speed and consistency of our studies, and enable high-throughput applications such as drug screening.

 

To carry out this work, we will use our multi-parameter imaging system in combination with studies of gene expression, and we will identify bioink formulations that produce 3D tissues that more closely resemble adult human hearts than current heart tissue models. This will have potential value in both drug discovery and drug toxicity assays. Ultimately, this project will allow us to identify therapies for patients.

Longitudinal, Deep-Phenotyped Pediatric Databank of Medical and Drug Therapy Outcomes

This sequencing project will enable improvements to drug safety and effectiveness for children by making genomic data on their responses and adverse reactions to various medications more widely accessible to researchers and health regulatory agencies.

Abstract: This project will leverage the existing resources of the Canadian Pharmacogenomics Network for Drug Safety (CPNDS) to bring a pediatric component to the Pan Canadian Genome Library and allow CPNDS to continue its work in making medications safer for children locally, nationally and internationally. Over the past 20 years, the CPNDS has collected DNA and biological samples from over 12,350 patients together with comprehensive demographic and clinical data that characterize their responses to over 100,000 medication uses and over 10,000 severe adverse drug reactions. This number is remarkable given that pediatric diseases like cancers are rare and severe adverse drug reactions are rare occurrences as well. Some patients have more than 40 years of longitudinal data. These patients were recruited and enrolled from 14 academic health centres in geographically diverse locations across eight provinces in Canada (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec, Nova Scotia and Newfoundland). This funding is critical for the continuation of this network.

This project has four primary objectives to support the Pan-Canadian Genomics Library (PCGL):

1. Contact previously recruited patients in the CPNDS databank and re-consent them for inclusion of their de-identified clinical and genomic data into the Pan-Canadian Genomics Library (PCGL)

2. Continue to prospectively recruit and enroll patients at our 10 existing study sites over the course of this four-year project (n=4,000). This additional recruitment will be conducted through the lens of significantly enhancing inclusion, diversity, equity and accessibility (IDEA) of the cohort. These samples are being added to ensure that future research beyond this project has a richer and more diverse database of clinical and genomic data to work with.

3. Improve the genomic data holdings from genome-wide genotype typing data (GWAS) to whole-genome sequencing data – short-read sequencing will be conducted for n=10,985 and long-read sequencing will be conducted for n=1,000. This will allow for much more in-depth investigations of drug-induced harm.

4. Conduct genomic analyses using the generated whole-genome sequencing data to explore and identify biomarkers that are predictive of drug-induced harm associated with seven severe adverse drug reactions experienced by pediatric oncology patients in Canada while facilitating dialogue and engaging with the multidisciplinary team assembled for this project. The generation of this data will facilitate research and innovation to improve drug safety and effectiveness in children by making these data more widely accessible to researchers from academic, charitable organizations, health centres, for-profit private companies and health regulatory agencies.

Link: https://genomecanada.ca/project/longitudinal-deep-phenotyped-pediatric-databank-of-medical-and-drug-therapy-outcomes/

Optimization of a tumor-specific antibody for the treatment of cancer

The McNagny and Roskelley research teams are thrilled to receive generous Matching Funds from Health Research BC in support of our 2025 GlycoNet Strategic Initiatives Grant from the Canadian Glycomics Network Centre of Excellence. This critical funding, made possible through Canada’s Networks of Centres of Excellence and Strategic Science Fund programs, will accelerate our mission to develop novel groundbreaking cancer immunotherapies.

 

Led by Prof. Kelly M. McNagny from the School of Biomedical Engineering and co-applicant Prof. Calvin Roskelley, both at the Vancouver Campus of the University of British Columbia, this project merges world-class academic expertise and cutting-edge industrial innovation. We are proud to collaborate with MetaStem Therapeutics (a UBC startup) and iProgen Biotech, two pioneering BC-based companies committed to bringing the next-generation of antibody drug conjugate (ADC) therapies to the clinic. Their invaluable industry expertise and in-kind support will help drive this research forward to meet a critical unmet clinical need in treating patients with metastatic cancer.

 

Our work builds on groundbreaking insights into the function of the stem cell glycoprotein, podocalyxin, a key driver of aggressive tumor cell behavior and an effective predictor of poor outcomes in most types of solid tumors. From these insights, we have developed a prototype ADC-based immunotherapy engineered to selectively bind and eliminate tumor cells while sparing healthy tissues. Based on these crucial findings, we will now refine and optimize our ADC to enhance its effectiveness against recurrent ovarian and pancreatic cancers, laying the foundation for the rapid transition of this therapy into clinical trials.

 

Our ultimate goal is to develop more effective, less toxic treatment options for patients battling these devastating cancers. Thanks to this generous support, we are one step closer to making this very novel therapeutic approach available to those patients for which there are currently few effective clinical options.

CHILD-BRIGHT: Child Health Initiatives Limiting Disability — Brain Research Improving Growth and Health Trajectories – Phase 2

Health Research BC is providing match funds for Phase 2 of the Network, which is funded by the Canadian Institutes of Health Research’s (CIHR) Strategy for Patient-Oriented Research (SPOR) Networks in Chronic Disease.

 

Supported through CIHR’s Strategy for Patient-Oriented Research and 15 generous funding partners, CHILD-BRIGHT is a pan-Canadian patient-oriented research (POR) network that focuses on brighter futures for children with brain-based developmental disabilities (BDD) and their families.

 

Dr. Dan Goldowitz, Professor Emeritus of Medical Genetics at UBC and senior scientist at the Centre for Molecular Medicine and Therapeutics at the BC Children’s Hospital Research Institute, is one of CHILD-BRIGHT’s three co-PIs, along with Drs. Steven Miller at UBC, and national PI Annette Majnemer at McGill University.

 

Our national Network of 350 researchers, clinicians, decision-makers, youth and parents have co-created a novel research program based on priorities identified by patient-partners and other stakeholders that incorporates new technologies and interventions to advance health practice and policy. In our initial phase (2016-22), thirteen projects focused on early intervention that promotes brain/child development, strategies that support mental health of children/families, and service delivery redesign that addresses gaps in service.

 

A major focus for our Network is moving research into action through insight, inclusivity and methods grounded in implementation science (IS) and knowledge mobilization (KM). In Phase 2 (2022-26), we will accelerate the uptake and use of the knowledge generated in Phase 1 to enhance child health and family well-being within BC and across Canada. Our goal is to become a movement for change by moving patients and families into research teams, moving research into practice and policy, and ultimately moving children and families forward to brighter futures.

 

Dr. Goldowitz is co-leading CHILD-BRIGHT’s Training and Capacity-building Program with implementation scientist Dr. Celia Laur from the University of Toronto. In concert with his UBC team, they will engage with relevant groups including patients and families, trainees, and researchers to build a comprehensive training program that will enhance core competencies in POR, KM, IS, and EDI.

 

In addition, a core Phase 2 project spearheaded by Drs. Hal Siden and Tim Oberlander will receive funding support.  “Pain and Irritability of Unknown Origin (PIUO): Implementing a Diagnostic Pain Pathway in Community Clinics” will translate the findings from Phase 1 into a readily available tool that can help community pediatricians systematically assess the potential root causes of pain and irritability in children with complex medical needs

 

Canadian Primary Care Research Network – Phase 2

Health Research BC is providing match funds for the BC Primary Health Care Research Network (BC-PHCRN) Phase 2, the BC node of the Canadian Primary Care Research Network (CPCRN), which is funded by the Canadian Institutes of Health Research’s (CIHR) Strategy for Patient-Oriented Research (SPOR) Primary Care Network. 

 

The goal of the BC-PHCRN is to encourage, facilitate, and support collaborations between government, health authorities, health professionals, patients and researchers. The CPCRN and BC-PHCRN objectives include:

  • Expand PBRLNs by recruiting new primary care practices and providers  to include more electronic medical record data for research purposes,
  • Participate in CPCRN research and quality improvement projects and other projects as well,
  • Support development of a pan-Canadian primary health care information system that integrates electronic medical records with Patient Reported Experience Measures (PREMs) and Patient Reported Outcome Measures (PROMs),
  • build a network of primary care researchers, patient partners, clinicians, decision-makers and trainees to facilitate communications and knowledge mobilization, and
  • build capacity in patient-oriented primary care research in BC and beyond.

In British Columbia, the network is participating in both funded and non-funded research projects. Funded projects include:

  • OECD PaRIS to measure the outcomes and experiences of health care that matter most to people,
  • SPIDER to deprescribe potentially inappropriate prescriptions among elderly living with chronic conditions, and
  • Choosing Wisely antibiotic prescribing to provide CPCSSN providers with portrait detailing their antibiotic prescribing for respiratory tract infections.

Non-funded projects include:

  • Evaluation of ICD-11 and ICPC-3 codes to build evidence for updating Canada’s Disease Classification Systems in primary care, and
  • Team-based care to understand functioning of teams in primary care.

The Nominated Principal Investigator of BC-PHCRN is Dr. Rubee Dev. Dr. Dev is an Assistant Professor in the UBC School of Nursing & Associate Faculty in the Centre for Health Services and Policy Research, University of British Columbia, with research foci in global health and primary health care nursing. Dr. Dev leads the BC PHCRN along with Dr. Nathaniel Hawkins who is also Director of Research and Associate Professor at the UBC Division of Cardiology.

Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) Network – Phase 2

Health Research BC is providing match funds for Phase 2 of the Network, which is funded by the Canadian Institutes of Health Research’s (CIHR) Strategy for Patient-Oriented Research (SPOR) Networks in Chronic Disease. 

 

The Can-SOLVE CKD Network is Canada’s largest-ever kidney research initiative. This national partnership of patients, researchers, health care providers, and policy-makers is working to transform treatment and care for Canadians affected by chronic kidney disease.

The network coordinates and conducts innovative research using a patient-oriented approach. During Phase 1 (2016-2023), 18 research teams developed projects seeking to diagnose kidney disease earlier, discover better treatments, and deliver innovative patient-centred care. These projects took many forms: treatment and education interventions, e-health decision aids, and clinical trials testing new therapies.

 

For Phase 2 (2022-2027), the focus shifts to mobilizing these innovations and implementing them into health care policy and practice on a national scale. The goal is to apply this knowledge to clinical practice in order to improve patient care. Can-SOLVE CKD Phase 2 also aims to change the culture of kidney research by strengthening Indigenous cultural competency and equity, diversity, and inclusion (EDI) in health research.

 

Patients have been central to these accomplishments. The network’s Patient Governance Circle has enabled a system in which all research activities are developed collaboratively by patient partners, researchers, and other key stakeholders.

 

In British Columbia, the network is delivering the Kidney Check program. This initiative brings point-of-care screening for chronic kidney disease and its risk factors to rural and remote First Nations communities. Mobile screening technology, including a custom-built iPad app, enables real-time result sharing and the creation of personalized treatment plans. The goal is to support early detection of kidney problems and ensure timely follow-up care. With appropriate treatment, fewer individuals will suffer from kidney failure requiring dialysis, resulting in better health for communities and lower costs for our health care system.

 

The Named Principal Investigator of Can-SOLVE CKD is Dr. Adeera Levin. Dr. Levin is the former president of the International Society of Nephrology and was awarded the Order of Canada in 2015 for her work’s impact on those living with chronic kidney disease. As Senior Medical Lead, Integration Clinical and Academic Networks at Providence Health Care, Dr. Levin has played an important role in facilitating implementation and impacting policy in British Columbia.

A Chemogenomic Platform for Identifying Orphan Glyco-immune Checkpoints

Health Research BC is providing match funds for this research project, which is funded by GlycoNet’s Collaborative Team Grant.

 

This Canada-wide project is a collaboration between Prof. Landon Edgar (University of Toronto, lead PI) and Prof. Simon Wisnovsky (UBC). Both PIs research the ways in which cellular sugar molecules control the activity of immune cells. All of the cells in our body are coated with different types of sugar molecules. Cells in our immune system have ways of “tasting” these sugars. Some types of sugars taste good to our immune system, signaling that our cells are healthy and that everything is normal. Other sugars (like those attached to invading bacteria, viruses or cancer cells) taste bad to our immune cells, triggering them to activate and try to protect us from disease. Sometimes our cells can become altered in ways that lead them to produce different or abnormal types of sugar molecules on their surface. When this happens, it can lead our immune cells to either overlook unhealthy cells (in the case of cancer) or inappropriately attack healthy cells (in the case of autoimmune diseases). Understanding the details of how this happens can help us develop new drugs to treat such diseases. We face the problem, however, that these cellular sugar molecules are not like the sugar that we eat. Cellular sugars are notoriously chemically complex, making it difficult to predict exactly how specific types of sugar molecules will affect our immune system. This proposal attempts to solve this problem by using advanced genetic techniques to better understand the ways in which immune cells interact with cell-surface sugars. The goal of the project is to identify specific proteins that bind to cancer-associated sugars whose activity can then be blocked for therapeutic purposes.

End of Award Update – April 2024

Results:

With our genome-wide CRISPR screening approach, we have identified several novel immune receptors that bind tumor associated carbohydrate antigens. We are currently seeking to validate these receptors as targets in immune oncology assays.

 

Impact & Potential Influence:

There is an urgent need to uncover novel targets for cancer immunotherapy. Our work has uncovered several tractable immune receptors that may be excellent targets for the development of novel immune checkpoint inhibitor therapeutics. In the long-run, our work lays the foundation for the development of broad-spectrum immunotherapies for a range of different cancer subtypes.

 

Next steps:

We are currently putting a grant application together to get this project funded in the longer term by the Cancer Research Society. We hope to publish a small methods-focused paper on this research in the coming year.

Dissecting regulation of the CD44-hyaluronan axis in cancer metastasis

Health Research BC is providing match funds for this research project, which is funded by GlycoNet’s Collaborative Team Grant. Additional funding is provided by the Cancer Research Society. 

 

This BC-based research project is a collaboration between UBC cancer researchers Prof. Simon Wisnovsky (lead-PI), Prof. Pauline Johnson and Prof. Cal Roskelley. The research of all three Principal Investigators focuses on defining ways that cellular carbohydrates can act as drivers of cancer progression. The majority of deaths due to cancer occur as a result of cancer spread (called metastasis). Thus, it is important to identify molecules that drive metastasis, in order to develop targeted therapies to limit cancer spread. Here, we will determine how one widely expressed cell surface molecule, CD44, drives metastasis and we will identify novel cellular factors that regulate this process. To do this, we will use mouse models of melanoma and breast cancer metastasis, where cancer cells spread to the lung. We will use cancer cells expressing particular forms of CD44, or mutated forms of CD44, and test whether the interaction of CD44 with a long sugar molecule (called hyaluronan or HA) promotes metastasis. We will also determine if one variant of CD44, CD44v6, drives melanoma metastasis. We will then use these mouse models to determine at which stage CD44-HA interactions and CD44v6 affect the metastatic process: migration, survival, or growth in the lung. Next, we will use two innovative high throughput screening approaches (siRNA and Crispr-Cas9) to identify genes that regulate CD44 binding to HA and CD44v6 expression in cancer cells. Putative regulatory genes will be validated, then cancer cells with these genes deleted will be tested in our mouse models of metastasis. Our goal is to identify new proteins that regulate CD44 functions and reduce metastasis. These proteins will provide new targets for intervention and the development of novel anti-metastatic therapies to help cancer patients both in BC and internationally.

End of Award Update – April 2024

 

Results:

In this project, we used advanced genetic techniques to identify genes that drive metastasis in breast cancer. We have uncovered a number of exciting potential targets that could be candidates for the development of anti-metastasis therapeutics.

 

Impact & Potential Influence:

Our results have significant translational potential, and we are excited to expand our research to validate hit genes from our studies as potential drug targets.

 

Next steps:

With the foundational data produced with this study, we have applied for funding from the Canadian Cancer Society and are also preparing a CIHR Project Grant application to fund this project long-term. Our goal is to systematically evaluate a set of novel hit genes as regulators of cancer metastasis using preclinical models, with the ultimate long-term goal of developing new therapeutics that can inhibit cancer metastasis.

Clinical Trial for Montbretin A (MbA) in Diabetics

Health Research BC is providing match funds for this research project, which is funded by GlycoNet’s Translational Grant. 

 

This fully B.C.-based project will undertake a Phase 1 human clinical trial of a promising natural product from plants, Montbretin A (MbA), for control of blood glucose levels in diabetics. The team comprises a chemist (Stephen Withers), a clinician (Robert Petrella), a plant biochemist (Joerg Bohlmann) and a biochemist/coordinator (J.P. Heale). Earlier B.C. work identified MbA as a potent inhibitor of amylase, the principal human enzyme that degrades starch in our guts leading to glucose release into the bloodstream. Subsequent studies in diabetic rats confirmed that orally administered MbA lowers blood glucose levels and is safe, even at very high dosages. On this basis Health Canada approved a Phase 1 clinical trial to evaluate the safety of MbA in humans. This funding will allow us to carry out that trial in a side-by-side evaluation with the drug acarbose that is currently used but causes unpleasant side effects. Due to its different mode of action of MbA should be better tolerated yet highly active.

 

Key words: diabetes, obesity, blood glucose, amylase, inhibitor

Breaking Barriers: Empowering Primary Care Providers to be Instigators of Change in Hearing Health Care Practice

Health Research BC is providing match funds for this research project, which is funded by the Vancouver Foundation’s Participatory Action Research Investigate Grant. 

 

Up to 65% of adults in British Columbia (BC) aged 60+ will develop hearing loss. Fewer than one-quarter of these adults use hearing health care, with most delaying treatment 7 to 10 years on average. Untreated hearing loss affects health-related quality of life with links to social isolation, depression, greater risk of falls, and reduced financial security. For adults with concerns about their hearing, primary care providers (PCPs) are often a first point of contact for help seeking, and yet for reasons that remain unclear, PCP referrals to hearing health care are inconsistently and infrequently practiced. This problem was identified as a top priority through focus groups conducted in 2020. These graphics illustrate the focus group discussions that led to the development of this research question.

 

We will use a community-based approach to identify reasons for lack of referral and develop strategies that empower primary care providers to be key instigators for increased, timely uptake of hearing health care by individuals with hearing concerns.

 

The research team, all based in BC, is led by Lorienne Jenstad, PhD, an audiologist and associate professor at the University of British Columbia; Brenda Poon, PhD, the research program lead at the Wavefront Centre for Communication Accessibility; and Ruth Warick, PhD, president of the Canadian Hard of Hearing Association, Vancouver Branch. The team works closely with other individuals who have lived experience of hearing loss, physicians, nurses, clinical audiologists, and community organizations.

 

Ultimately we hope that primary care providers and the general public will have better recognition of the importance of hearing health and better understanding of the process to receive hearing health services, leading to timely uptake of hearing health care by individuals with hearing concerns and the potential to improve long-term health outcomes.

 

 

End of Award Update – February 2025

 

Results

We were interested in learning how to empower primary care providers (PCPs) to champion hearing health care. Our data collection and partnerships led us to the online platform Pathways BC as the go-to resource for PCPs. We found that Pathways contains very little information about hearing health for adults. Thus, our work can fill an identified gap (providing an algorithm for hearing health care for adults) on a platform that PCPs use regularly in their work.

 

We learned about systemic barriers to supporting adult hearing health by PCPs. Distrust of audiology (from patients and PCPs) with respect to places that sell hearing aids seemed to lead to a reluctance to make referrals for hearing health care. PCPs noted that time was a factor influencing their referral of patients to hearing health care. As noted by one PCP, discussion of hearing health with the patient would depend on “if I have the time to think of it when the patient did not come in with that specific problem or did not come in for an ear problem.”

 

 

Impact

Through our 3-year project, we identified recommendations for promoting hearing health for adults by PCPs in BC, and we developed (with our community advisory group) the content, format, and venue of a hearing health resource for PCPs. We identified that primary care providers hold an important role in promoting hearing healthcare for older adults; yet they encounter multiple barriers to providing optimal hearing health.

 

 

Potential Influence

As non-PCPs, we’ve learned about how PCPs navigate the system and how they want to access information, which has led us to explore opportunities for adding hearing-related data fields into electronic medical records in BC.

 

 

Next Steps

We will work with the online platform Pathwaysbc.ca that is frequently used by primary care providers in BC to access referral and patient information to finalize a hearing health resource for PCPs.

 

As identified through our research, the resource should include the following three learning objectives: 1. Identify/implement strategies for optimal communication with patients who have hearing loss; 2. Determine between a referral to an audiologist or ENT; 3. Use a specific validated tool to screen for hearing loss The format of the hearing health resource should be a one-page flowchart to aid in clinical decision making for older adult patients who report hearing concerns The venue for the resource will be the online platform Pathwaysbc.ca

 

Our plan for the next ~ six months is to finalize the product for primary care providers to access on Pathways BC, develop and deliver several Continuing Professional Development (CPD) sessions for primary care providers to orient them to the new Pathways resource and provide more context.

 

We will conduct evaluation studies regarding the hearing health resource we have developed for PCPs.