Extracellular vesicle associated glycans as a novel platform for breast cancer detection

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

 

Breast cancer is the most common cancer amongst women in Canada. Breast cancer cells shed tiny pieces of themselves into the blood stream called extracellular vesicles. These tiny pieces, or cell fragments, are different from those of a healthy breast cell and we think they could be used to detect a breast cancer at its earliest stage. Importantly, we can isolate and study these fragments from the blood of healthy females and breast cancer patients. We think that by looking at the sugars and proteins they contain we will find markers that could help in the detection of breast cancer. We are also going to look at tumor cell fragments from patients whose cancer came back years after treatment, a process known as metastasis, and find unique markers that could predict this outcome. By identifying breast cancer early and figuring out whose at risk for a having their cancer come back we can improve how women are treated and reduce the chances of the cancer coming back.

 

This Pan-Canadian project involves research teams in British Columbia and Alberta. Dr. Williams, lead PI, is an assistant professor at UBC’s Faculty of Pharmaceutical Sciences and her team includes clinical pathologist Dr. Peter Watson (BC Cancer) and Professor of Chemistry Dr. Lara Mahal (University of Alberta).


End of award update: November 2021

 

Most exciting outputs

Our project successfully isolated small cell fragments, termed extracellular vesicles, from blood plasma of hundreds of breast cancer patients and healthy females. From this, we were able to look at the sugars and proteins on these fragments to identify ones unique to breast cancer patients. This has allowed us to find a couple unique markers that we think can be used to identify breast cancer at its earliest stage of development.

 

Impact so far

Detecting cancer at the earliest stage will support the best outcome for patients. This is particularly relevant in breast cancer as it is well established that a disease diagnosis at an early stage, Stage I, is associated with the highest rates of patient survival. Our project has identified novel sugar and protein based biomarkers with utility in identifying breast cancer. Validation of newly identified biomarkers could lead to the development of a blood-based test for breast cancer screening.

 

Potential future influence

Our project aims to reduce the mortality associated with a breast cancer diagnosis. To do this we are aiming to develop a non-invasive test that will support the detection of breast cancer at its earliest stage.

 

Next steps

We plan to validate our newly discovered breast cancer biomarkers and work towards translating our results into a product that could be used as a simple point-of-care test by a family doctor.

Please visit GlycoNet to learn more about this project.

The EARLY study: Economic evAluation of a novel pRostate cancer gLYcan-based diagnostic tool

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

 

Early detection of prostate cancer uses methods that are controversial and lead to uncertainty in care; this leads to a lot of overdiagnosis and overtreatment in men who are healthy or have inactive disease. We recently developed a test using a sugar found on aggressive cancer cells that acts as a biomarker to detect high-risk cancer in patients and support biopsy decision-making. But, for this test to be taken up in Canada to improve patient care, it needs to be evaluated for its potential value for money for the healthcare payer. This pan-Canadian project is the first analysis of the cost-effectiveness of a new sugar-based prostate cancer diagnostic tool. It will tell us whether the maximum possible gains from the new test versus status quo (or other new technologies) are worth their costs, and in which subgroups of patients we see the most positive net benefit.

 

The leading PI is Dr. Conklin, assistant professor at UBC’s Faculty of Pharmaceutical Sciences and scientist at UBC’s Centre for Health Evaluation and Outcome Sciences (CHEOS). Dr. Conklin’s BC-based team include Drs. Wei Zhang and Larry Lynd (also Scientists at CHEOS) and Dr. Williams (inventor of the new sugar-based test); the team also includes Dr. Liu, a clinician collaborator from Sunnybrook Hospital in Toronto.

 

This economic evaluation project will address a critical gap in test development early on to avoid the pitfall of creating an economically non-feasible test. The output of this project could contribute to improved patient care and to better decision-making of patients, guideline developers and health ministers.

 

Please visit GlycoNet to learn more about this project.

Towards clinical implementation of pharmacogenomics to improve the treatment of people with depression in BC

This award is being co-funded by Michael Smith Health Research BC, Genome BC, and Genome Canada.

 

In Canada, more than 1 in 10 people will suffer a major form of depression at some point in their lives. There are many effective treatments for depression, including drug therapy. Finding a medication that both works and does not cause severe side effects is often a matter of trial-and-error. This may contribute to the high non-adherence rates and, subsequently, to poorer health outcomes and increased costs. An individual’s genetic makeup is thought to be partly related to whether particular drugs work and whether there are side effects with the drug. “Pharmacogenomic” testing, that is, using the patient’s genetic information to determine which particular drug might work best, at the right dose, with the fewest side effects, is a new and promising approach.

 

In this study, we want to know if pharmacogenomic testing for depression treatment should be routinely used in British Columbia. Through a series of research activities, we will evaluate how much improved health patients might see, as well as whether the testing is good value for money for the health system. As a whole, the project will provide tools for evaluating and addressing societal and economic considerations for the implementation of pharmacogenomics tools into clinical practice.

 

Dr. Stirling Bryan (Principal Investigator) is a health economist, Professor in UBC’s School of Population and Public Health, a Senior Scientist at the Centre for Clinical Epidemiology and Evaluation (Vancouver Coastal Health Research Institute), and President of the BC Academic Health Science Network. Dr. Jehannine Austin (co-Principal Investigator) is a genetic counsellor, Professor in Psychiatry & Medical Genetics at UBC and executive director of the BC Mental Health and Substance Use Services Research Institute. The remaining multi-disciplinary Canadian team has expertise in health policy research, simulation modeling, systematic reviewing, knowledge translation, and includes patient partners.


Project Update – February 2022

Pharmacogenomic Testing for Major Depression: A Simulation Model

To provide your thoughts on the model described in the video, please contact:

Louisa Edwards, PhD
Research Program Manager
School of Population & Public Health
University of British Columbia
Email: louisa.edwards@ubc.ca

 

Useful Links

A scoping review of literature on different models of allocating funds to facilitate integrated care

Health Research BC is providing match funds for this research project, which is funded by CIHR’s Strategy for Patient Oriented Research (SPOR) Primary and Integrated Health Care Innovations (PIHCI) Network – Knowledge Synthesis Grants.

 

Jason Sutherland is Professor in UBC’s Centre for Health Services and Policy Research in the School of Population and Public Health. He is also a Scholar of the Michael Smith Foundation for Health Research.

 

This is a two-province research team, though the scope of the project is examining integrated funding models across the globe. Little is known regarding how other countries have developed and implemented policies for supporting integrated healthcare. This study will conduct an extensive review of the literature and synthesize the evidence regarding the scope and breadth of policies and their effectiveness to improve integration of healthcare across sectors of the delivery system.

 

Knowledge translation activities:

  • Policy roundtable to disseminate findings to knowledge users in Calgary, Alberta
  • Policy roundtable to disseminate findings to knowledge users in Vancouver, British Columbia
  • Patient Groups Compensation (honorarium, travel cost, parking) in Calgary, Alberta
  • Patient Groups Compensation (honorarium, travel cost, parking) in Vancouver, British Columbia
  • Open Access Publication jointly by University of Calgary and University of British Columbia
  • Webinar and YouTube video preparation by the University of British Columbia

The team expects to share findings of the project with key public stakeholders regarding attributes of policy and delivery systems that integrate sectors of the healthcare delivery system to improve care and outcomes.


End of Award Update – April 2022

Most exciting outputs

In my opinion, the most exciting outputs from this project include the development of a multi-institution collaborative to collect surgical patients’ health and health outcome information. The information that this project has generated has led to innovative insights into the value of operative treatment for the patient, health system and government. This information has led to creative ways of re-configuring access to elective surgery, improving mental health in addition to physical health, and training students on the importance of patients’ perceptions of their health.

 

Impact so far

The impact of this project is local, national and international. Locally, operative patients, the health system and the province are benefiting from understanding the gain in health attributable to surgery. Nationally, this work is garnering significant attention from outcomes researchers and health systems seeking to understand variability in health and healthcare outcomes from surgical care. Internationally, this work is attracting interest from countries with public health systems with similar problems in accessing surgical care and cost-efficiency of healthcare delivery, international agencies, such as the International Consortium for Health Outcomes Measurement (ICHOM), and academic institutions.

 

Potential future influence

The project is continuing to expand with financial and in-kind support from new organizations. In 2021, PHSA and the Heart and Stroke Foundation (B.C.) began funding the expansion of the project.

 

Next steps

  1. Continued expansion with existing and new collaborators.
  2. Renewed knowledge translation with government and healthcare organizations.
  3. Attract new funding from national and provincial research organizations.

Useful links

Scaling up Trauma and Violence Informed Outreach with Women Affected by Violence

Health Research BC is providing match funds for this research project, which is funded by a Social Science and Humanities Research Council of Canada (SSHRC) Partnership Grant. Additional support is provided by UBC (Vancouver and Okanagan) and an anonymous donor.

 

Through community-based research design and implementation we aim to address an urgent priority of providing access and receipt of services among women and youth affected by violence who experience the worst severity in terms of types, duration, frequency and impact of violence for their lives. This pan-Canadian team includes 31 co-investigators and 14 partner organizations, across academic, public service, not for profit and private organizations.

 

Together, this team will implement an innovative, trauma and violence informed approach to outreach and community service integration in 4 Canadian cities including two in BC, testing the efficacy of this model to positively impact women’s engagement with an array of health and social services that can help women recover from and prevent ongoing violence in women’s lives. Study outcomes will provide essential information about the current primary care services in the BC Sites, and offer evidence informed strategies with transferability within these and other BC locations to enhance primary care for vulnerable women.

 

Additionally, because our model includes an integrated service approach we will be investigating how not-for-profit service organizations navigate and collaborate with primary care services to support appropriate referral for the women to whom they provide services. This information can also support more effective collaborations between these two service provider sectors.

 

The principal investigator is Victoria Bungay, Associate Professor, School of Nursing, UBC-Vancouver and Canada Research Chair in Gender, Equity and Community Engagement. Other BC team members are:

  • Jennifer Baumbusch, School of Nursing, UBC-Vancouver
  • Aggie Black, Providence Health Care
  • Linda Dewar, Inner City Women’s Initiatives Society
  • Kasari Govender West Coast Legal Education and Action Fund (West Coast LEAF)
  • Kim Hawkins, Rise Women’s Legal Centre
  • Angie Lohr, H.O.P.E. Outreach in Kelowna
  • Karen Mason, Kelowna Women’s Shelter
  • Michelle Novakowski, Central Okanagan Elizabeth Fry Society (COEFS)
  • Will Panenka, Department of Psychiatry, UBC-Vancouver
  • Eli Puterman, School of Kinesiology, UBC-Vancouver
  • Paul Van Donkelaar, School of Health & Exercise Sciences, UBC-Okanagan

 

The team also includes an incredible advisory of women with expert knowledge in accessing supports and services within their respective communities.

 

Learn more: “Scaling Up” project website

An Inter-provincial comparison of innovative programs that help individuals and families affected by life-limiting chronic illnesses navigate end-of-life

Health Research BC is providing match funds for this research project, which is funded by CIHR’s Strategy for Patient Oriented Research (SPOR) Primary and Integrated Health Care Innovations (PIHCI) Network – Comparative Program and Policy Analysis Grant. 

 

Dr. Kelli Stajduhar is working with a team of researchers across Canada including PI R. Urquart (NS), and Co-Is K. Pfaff (ON), G. Johnston (NS), B. Lawson (NS), C. Tschupruk (NS), and G. Warner (NS). Using a realist evaluation, survey questionnaires, and in-depth interviews with program personnel, programs users and family members, this study will focus on gaining an improved understanding of innovative community-based navigation programs across Canada with a focus on end-of-life care and support.

 

Of particular interest are those programs that have been developed and successfully put into place across various health jurisdictions and which help educate patients and families, link them to critical health system and community services and supports, and facilitate coordination of services and supports across healthcare settings. Generally speaking, the programs of interest will help patients access the services and resources they need, though it’s expected the way in which they do so will vary from program to program.

 

It will be examined 1) whether and how these navigation programs work across different community and health system contexts; and 2) what is needed to integrate successful community-based navigation programs into currently existing primary healthcare services and systems of care so they are sustainable, and can improve patient and family outcomes across Canadian jurisdictions and healthcare settings at the end-of-life.

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

Supporting integration through primary health care teams: A comparative policy analysis across four Canadian provinces

Health Research BC is providing match funds for this research project, which is funded by CIHR’s Strategy for Patient Oriented Research (SPOR) Primary and Integrated Health Care Innovations (PIHCI) Network – Comparative Program and Policy Analysis Grant. 

 

Dr. Nelly Oelke is undertaking this pan-Canadian project across four provinces (BC, AB, ON, and QC) with a team of researchers including the following PIs: S. Montesanti (AB), S. Johnston (ON), and M. Breton (QC).

 

Primary health care (PHC) models in Canada continue to change. There are still many gaps in understanding what works and what doesn’t work for PHC teams, specifically, to promote integration and continuity of care for patients with complex needs (e.g. more than one chronic condition). The goal of this research is to study provincial and regional policy documents (guiding principles and courses of action) that support health services integration for patients with complex needs through PHC teams. Patient engagement in developing and applying policies will also be looked at.

 

This study will include three phases.

  • Phase 1: Collecting and analyzing all policy documents from the four provinces. Individual case reports will be developed and then policies will be compared across provinces.
  • Phase 2: Patient interviews from each province and then a disussion session with those patients to review the results and come up with an action plan.
  • Phase 3: Feedback will be gathered through online and web-based discussions from a broad group of provincial and national stakeholders including patients. These stakeholders will be asked to develop recommendations and actions based on the research results.

The results of this study will provide a better understanding of BC’s current policies for PHC teams, and how these support or create barriers to integrated health services delivery. It will also provide a better understanding of how BC patients and caregivers are involved in developing and applying policies in this area. Given BC’s focus on primary health care transformation, these will be most beneficial in supporting change.

 

Finally, the study will provide a set of leading national practices for integrated health services delivery through PHC teams that will be helpful to all participating provinces, other provinces in Canada, and internationally.


End of Award Update: May 2022

Most exciting outputs

 

1. Primary Health Care (PHC) teams need to be integrated at the individual level (at the point of care to improve patient’s care), PHC teams also need to be integrated at the health system level to facilitate integrated health services delivery.

  • Clearly defined roles for team members are needed for effective PHC teams.
  • Strong support for co-located teams, but not always feasible given geography, and the increase in virtual care. More research is needed in comparing co-located and virtual teams, particularly in today’s context of increased virtual care delivery.
  • Interoperability and access to electronic health records, impacts team functioning. An accessible and shared electronic health record is needed for teams to function effectively.
  • Financial remuneration models continue to impact effective functioning of PHC teams.
  • Limited structure and information exist on performance measurement in PHC teams and integrated health services delivery. More work is needed at both the clinical and health system levels in performance measurement.

2. Ontario was more advanced in terms of engaging patients in policy activities, however, patients, family members, and caregivers who were engaged had similar experiences in policy engagement across the provinces. Patients were more often engaged in the development of policy, but engagement throughout the policy process (development, implementation, and evaluation) was much less clear.

3. Three key themes were identified: motivation for policy engagement, experiences with policy engagement, and barriers to engagement in policy, such as opportunities for engagement, power imbalances, tokenism, bureaucracy, accessibility, racism, sexism, and ageism.

4. Training in policy for patients, family members, and caregivers is needed to be better engaged throughout the policy process.

5. Opportunities for patients, family, and caregivers to engage in policy should be increased to facilitate inclusiveness and increase the diversity of perspectives.

 

Impacts so far

 

Our policy analysis on PHC teams and integrated health services delivery in four provinces in Canada, is to our knowledge the first of its kind. Our research results have been shared and we have discussed the same with the Primary Care, BC Ministry of Health. We have also shared the results of patient engagement in PHC policy with various stakeholders via the Putting Patients First Conference and the Canadian Association for Health Services and Policy Research Conference. Policy analysis results were also shared with international audiences through conferences and publications.

 

Potential future influence

 

Our research results have the potential to improve integrated health services delivery through PHC teams and to increase patient, family member, and caregiver engagement in PHC policy. The findings of the study can be utilized by other projects investigating what really makes PHC teams work, and which also include a policy analysis as well.

 

Next steps 

 

Knowledge translation: A virtual national knowledge translation event with patients, researchers, policymakers, decision-makers, and providers to share the results, as well as gather feedback on the findings. We will also share the results via plain language summary, infographics, and publications in academic journals.

 

Useful links

Cultural agility in Northern BC’s healthcare system: Increasing Indigenous employment participation and responsiveness to Indigenous well-being

Health Research BC is providing match funds for this research project, which is funded by a Social Sciences and Humanities Research Council (SSHRC) and Canadian Institutes of Health Research (CIHR) Healthy and Productive Work Partnership Grant. 

 

Primary Investigator Dr. Sarah de Leeuw and Co-Investigator Dr. Margo Greenwood, together with northern and provincial partners, lead a five-year, 1.3 million research project focused on further enhancement of Indigenous health and the healthcare climate in northern BC.

 

“Cultural agility in Northern BC’s healthcare system: Increasing Indigenous employment participation and responsiveness to Indigenous well-being” aims to bring about a more culturally safe and humble health care environment in which to both provide and receive care, as well as inspire new generations of Indigenous professionals to join the healthcare systems of northern BC.

 

Funded through the SSHRC and CIHR, this is the first joint federal research partnership grant of its kind to be held at UNBC, and one of only nine such grants held across Canada. The work builds on a pilot project launched in 2016, with both projects part of the joint “Healthy and Productive Work Initiative”.

 

Central partners include Northern Health (NH), National Collaborating Centre for Indigenous Health (NCCAH), the Michael Smith Foundation for Health Research (MSFHR), Two Rivers Gallery, and the UNBC Office of Research. The project also includes and builds upon numerous new and existing Indigenous and non-Indigenous community partners and collaborators across the north. These include the First Nations Health Authority, the Northern Medical Program, UBC, McMaster University, the Rural Coordination Centre of BC, BC Cancer, Carrier Sekani Family Services, Central Interior Native Health Society, and the Prince George Nechako Aboriginal Employment and Training Association.

 

The partnership team coming together for this project leans heavily on a history of relationship, commitment, creativity and innovative problem-solving, and a continued need exists for strong relationships, individually, organizationally and systemically, within the shared goal to enhance culturally respectful and safe healthcare practice in northern BC.

Targeting amyloid propagation in Alzheimer disease: Structures, immunology and extracellular vesicle topology

Dr. Neil Cashman is one of five BC researchers supported through the British Columbia Alzheimer’s Research Award. Established in 2013 by the Michael Smith Foundation for Health Research (MSFHR), Genome British Columbia (Genome BC), The Pacific Alzheimer Research Foundation (PARF) and Brain Canada, the goal of the $7.5 million fund is to discover the causes of and seek innovative treatments for Alzheimer’s disease and related dementias.

 

As the incidence of Alzheimer’s disease (AD) continues to increase worldwide, a treatment or prevention for AD is a top priority for medical science. One of the main hallmarks of the disease are protein plaques that form inside the brain, and are believed to be the primary cause of brain cell (neuron) death. Research has shown that the protein, amyloid-β (A-beta) is the main component of these plaques.

 

While there are many forms of A-beta produced by brain cells, the specific one that causes AD is hotly debated by scientists. Dr. Neil Cashman, a neuroscientist and neurologist at the University of British Columbia (UBC) has discovered a novel way of identifying a unique form of A-beta that can become toxic and inflict the damage associated with AD.

 

Cashman, who holds the UBC Canada Research Chair in Neurodegeneration and Protein Misfolding, and his team have discovered immunological compounds that specifically recognize the potentially toxic form of the A-beta protein, and can exclusively detect this form in the brains and spinal fluids of AD patients. Furthermore, Cashman found that normal, healthy control patients did not have this dangerous form of A-beta. It was also found that some healthy people naturally develop immune responses against their A-beta oligomer-specific target.

 

Cashman’s team will exploit this knowledge and their unique tools to learn how toxic A-beta proteins can spread from cell-to-cell and region-to-region in the brain causing AD. The discoveries by Cashman’s lab may provide an effective early diagnostic tool for the disease, and ultimately could lead to the development of a preventative vaccine to neutralize the toxicity of abnormal A-beta, potentially slowing or stopping the spread of neurodegeneration in the brain.

 


End of Award Update

Source: CLEAR Foundation

 

What did we learn?

We know that Abeta oligomers, a “seeding species” in Alzheimer’s disease, are predominantly spread in the brain via naked protein aggregates, and not through extracellular vesicles.

 

Why is this knowledge important?

The development of oligomer-specific antibodies (Acumen, ProMIS Neurosciences) has enabled selective immunotherapies for Alzheimer’s disease that target the toxic molecular species of AD, while sparing precursor protein (APP), Abeta monomers, and Abeta fibrils in the form of plaques. Binding to any of these non-oligomer molelcular species of Abeta lead to adverse effects, most prominently plaque-disruption linked ARIA – a form of neurovascular brain edema.

 

What are the next steps?

Dr. Cashman is now the full-time Chief Scientific Officer of ProMIS Neurosciences, which is conducting IND-enabling studies of the oligomer-specfic antibody PMN310. Human phase 1 trials are set for late 2022 or Q1 2023.

 

Publications