Building bespoke artificial cells and tissues on a chip for drug discovery

Human cells are fascinating and complex: they reproduce, break down food to create energy and communicate with each other. The ‘skin’ of the cell, the cell membrane, plays a crucial role in choreographing interactions between a cell and the outside environment, for example by allowing or prohibiting the access of drugs from the cell exterior to the cell interior.

I design and build lab-on-a-chip devices, which are plastic chips the size of a postage stamp inside of which I can manipulate tiny amounts of liquids. I use these lab-on-a-chip devices to create artificial cells to be able to study how the cell membrane regulates access to the cell interior. Human cell membranes have lots of different components that are used to transport drugs into and out of the cell.

Since the cell membrane is complex, we do not always know exactly which component is interacting with the drug molecule, and what effect it has. The cost of developing a new drug is around 2.6 billion USD and a significant proportion of drug candidates fail because we cannot predict how they interact with cells.

My research will help design drugs that can interact with cells more efficiently, so that they can get inside the cell in order to work properly.

Managing the Risks of Future BC COVID-19 Outbreaks Using Mathematical and Statistical Modelling.

Cases of COVID-19 have gone undetected, likely causing future waves. The aim of our research is to develop mathematical and statistical tools for the early detection of future BC COVID-19 waves, and to evaluate control strategies for a future wave. A key component is the estimation of unreported cases and the probability of transmission in high-risk subgroups (such as the elderly and homeless). Our mathematical model will determine disease spread and testing policies interactions. We will then identify early detection strategies for future waves. To track the patterns of individual behaviours and evaluate intervention strategies, we will develop a computer simulation model. With other provinces facing the same problems, our tools can be applied to the national pandemic.

Evaluating and optimizing rural and urban lesbian, gay, bisexual, transgender, queer, intersex, and Two-Spirit (LGBTQI2S) engagement with hospice and palliative care in the Island Health Region

Existing research focused on the experiences of gay and lesbian older adults with the health care system report that there is a general distrust and reluctance to access healthcare based upon the cumulative effect of discrimination over the life course. At present, while 75% of Canadians have indicated they would like to die at home, 45% of Vancouver Island residents die of in acute care. Clearly there exists a service gap and it appears possible that such a gap may be larger in the LGBTQI2S community. It is therefore vital to explore the level of LGBTQI2S engagement with hospice and palliative care, in order to ensure this population is not further marginalized in end-of-life. Victoria Hospice and Island Health will facilitate access to healthcare service providers, and I will recruit rural and urban LGBTQI2S participants and their families throughout the Island Health region via the relationships I have built with community gatekeepers. A Participatory Action Research strategy will be used and a Community Steering Committee of older LGBTQI2S people representing various geographies as well as sexual orientations and gender identities will be established. The Community Steering Committee will become an integral part of the Project Working Group, comprised of healthcare service providers, Island Health, Victoria Hospice, and the University of Victoria supervisory team and will be integrated into every step of the research process including development of research questions, refining research objectives, participant recruitment, data collection and analysis, evaluation of our findings, and knowledge translation.

3D bioprinting personalized neural tissues for drug screening

Bioprinting can produce living human tissues on demand, opening up huge possibilities for medical breakthroughs in both drug screening and developing replacement tissues. The Willerth lab was the first group in the world to use the cutting edge RX1 bioprinter from Aspect Biosystems to bioprint neural tissues similar to those found in the brain using stem cells derived from healthy patients. Similar tissues can be printed using stem cells derived from patients suffering from Parkinson's disease, recapitulating the disease phenotype in a dish. These highly customized, physiologically-relevant 3D human tissue models can screen potential drug candidates as an alternative to expensive pre-clinical animal models.

This project will bioprint both healthy and diseased neural tissues using our novel bioink in combination with Aspect Biosystems' novel trademarked Lab-on-a-Printer system and evaluate their function. We will then validate these tissue models as tools for drug screening by exposing them to compounds with known toxicity to brain tissues.

Dr. Willerth has over 16 years of experience in the area of biomaterials and tissue engineering, making her the ideal choice to lead this project. This project will lead to better health outcomes for patients suffering from neurological diseases and disorders, which account for 6.7% of the healthcare burden in Canada and improve the quality of life for B.C. residents suffering from such diseases.

A smart multifunctional wound dressing for continuous monitoring and treatment of chronic injuries

Wound management is a major global challenge and poses a significant financial burden to the healthcare system due to the rapid growth of chronic diseases such as diabetes, obesity, and aging population. The ability to detect pathogenic infections and release drug at the wound site is of the utmost importance to expedient patient care. We recently developed an advanced multifunctional dressing (GelDerm) capable of colorimetric measurement of bacterial infection and release of antibiotic agents at the wound site. We demonstrated the ability of GelDerm to detect bacterial infections using in vitro, ex vivo, and small animal tests with accuracies comparable to the commercially available systems.

Wireless interfaces to digital image capture hardware such as smartphones were used as a means for quantitation and enable the patient to record the wound condition at home and relay the information to the healthcare personnel for following treatment strategies. Additionally, we showed the ability of GelDerm to eradicate bacteria by the sustained release of antibiotics.

In this I2C application, we propose to support the commercialization of GelDerm through

  1. developing a multi-nozzle automated dispensing system as a scale-up manufacturing methodology for producing high volumes of GelDerm,
  2. developing a sterile packaging strategy for long-term storage of GelDerm and
  3. performing preclinical safety and performance studies in porcine model.
     

Employing A Choir to Reduce Dementia-Related Stigma: A Toolkit for Knowledge Mobilization

Co-leads:

  • Debra Sheets
    University of Victoria
  • Marilyn Malone
    Island Health

Trainee:

  • Mathilde Cervantes
    University of Victoria
  • Timothy Lukyn
    University of Victoria
  • Michaella Trites
    University of Victoria
  • Sebastian Santana
    University of Victoria

Over half a million Canadians are living with dementia, and 25,000 new cases are diagnosed each year. The estimated costs of dementia exceed 10.4 billion per year (Alzheimer Society of Canada, 2018). Dementia refers to a set of symptoms that include progressive, degenerative declines that affect memory, reasoning, the ability to communicate, judgment, and mood (Dugeon, 2010; Wetzels et al., 2010).

Alzheimer's is the most common cause of irreversible dementia and the numbers of people with dementia are projected to double by 2031. One of the biggest issues facing people living with dementia is the stigma and social isolation they face within their communities. Social isolation and loneliness significantly affect the quality of life of persons living with dementia and their caregivers. Social engagement can delay or reduce dementia symptoms and possibly decrease the rate of disease progression (Tuokko & Smart, 2018).

An intergenerational dementia choir can allow persons living with dementia to participate and contribute in meaningful ways to the broader community. Our research on intergenerational choirs indicates that they can significantly reduce the stigma of dementia and the social isolation. Choirs are inexpensive and common in most communities but a social movement is needed to make them dementia friendly.  Knowledge mobilization of our research findings will encourage stakeholders to explore ways to sustain and replicate our innovative intergenerational choir program.  

New strategies for unclogging microcirculatory obstructions in the healthy and diabetic brain

Recent work from our laboratory has shown that the brain capillaries routinely get 'stuck,' clogged by cells and debris even under healthy conditions. Most of these clogged capillaries clear within seconds to minutes, however, some can remain stuck for much longer. We also reported that about one third of these clogged capillaries were eliminated from the blood vessel network and never get replaced. Importantly, there are certain conditions which can increase the risk of clogged blood vessels in the brain such as diabetes. However, we still do not have a good mechanistic understanding of how these capillary obstructions can be cleared, or even what impact they have on brain function.

In this study, we will characterize capillary obstruction and pruning rates in healthy and diabetic mice brain. Next, we will focus on devising new strategies to enhance the clearance of capillary obstructions. At various time points, the mouse brain will be imaged to assess obstruction clearance and capillary elimination rates. These aims will provide new insights into microcirculatory changes that occur in healthy and diabetic brains, as well as a mechanistic understanding of how capillary obstructions can be cleared.

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

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). MSFHR has contributed matched-funding to support the CIHR Strategy for Patient-Oriented Research funding. 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.

Embedding Health Care Technologies in Real-World Contexts: Developing the Scale-up, Spread and Sustainability of Assistive Technologies in Homes, Communities and Health Systems

Co-leads:

Executive sponsor:

  • Heather Davidson
    BC Ministry of Health

Too often, promising technological innovations are not adopted, are abandoned or face other serious challenges to their uptake, spread and sustainability in real-world contexts (including in people’s homes, community settings, or health systems more broadly). This project aims to apply a new framework for theorizing and evaluating this phenomenon to several innovative assistive technologies (ATs) currently being developed in British Columbia for older adults.

By using a community-based participatory research methodology, the team will bring researchers, key health system decision-makers, technology developers, caregivers and older adults together into an inquiry team, focused on overcoming challenges to embedding ATs in end-users’ real-world contexts and identifying positive factors that support their uptake, spread and sustainability.

This project will directly address two BC health system priorities. Focusing on patients with complex medical conditions as well as the commitment to keeping seniors in their homes as long as safely possible (aging in place), the ATs are focused on improving the health and quality of life of older adults living with complex care needs and multiple chronic health conditions, as well as the onset of frailty.

The research will also contribute to enhancing access to effective primary health care. ATs are a crucial medium for enhancing access to primary health care, as many of the innovations are aimed at making communication and interventions between older adults and their primary health-care practitioners, including physicians, nurses and home support workers more effective.

The project’s objectives are to:

  • Contribute to the body of knowledge concerning effective implementation science approaches to the uptake, spread and sustainability of assistive technologies in home and community care settings.
  • Provide the provincial health system with a more effective framework for innovative technology assessment and evaluation and to give BC Ministry of Health and provincial health authority staff training opportunities in using the framework.
  • Directly improve the uptake, spread and sustainability of promising ATs in British Columbia.
  • Develop and sustain effective partnerships between the research community, the BC Ministry of Health, CanAssist and other relevant organizations.

Priority setting for children’s right to protection in BC: A knowledge mobilization symposium

Co-leads:

  • Ziba Vaghri 
    University of Victoria
  • Deborah Chaplain 
    Vancouver Island Health Authority
  • Bernard Richard
    Representative for Children and Youth of BC

Team member:

  • Sally (Yue) Lin
    University of Victoria

Trainee:

  • Lindsay Shaw 
    MA student

Dr. Ziba Vaghri and her research user co-leads — Mr. Bernard Richard and Ms. Deborah Chaplain — propose a knowledge mobilization symposium with participants from a range of advocacy organizations, policy makers, service providers, and researchers in the areas of child rights and/or early child development (ECD) across British Columbia (BC).

The symposium is a stakeholder engagement event with a goal of improving the state of ECD in BC. It will support evidence-based decision-making by presenting data collected in the pilot of the Early Childhood Rights Indicators (ECRI) in BC. 

ECRI is a comprehensive child rights monitoring tool for young children aged 0 – 8. The innovative ECRI tool is a series of indicators designed to verify the state of rights relevant to young children, as articulated in the United Nations Convention on the Rights of the Child (CRC); it aims to enhance children’s health and development through fulfilling their rights. The user-friendly digitized tool combines the indicators framework with information technology to facilitate the monitoring of existing capacities to support child rights, and to measure their impact on children’s health and development. Such information will be useful for policy makers, researchers, and service providers concerned with evidence-based decision-making.

The symposium objectives are to:

  1. Inform stakeholders of the findings of the ECRI BC pilot.
  2. Bring guest speakers to present the current state of knowledge on issues outlined in the pilot report to further inform stakeholders.
  3. Engage participants in constructive dialogue to discuss priorities for child protection in BC.

The symposium outcomes are to:

  1. Raise participants’ awareness of the status of child rights for young children in BC.
  2. Increase communication and collaboration between child rights and ECD stakeholders in BC, as these two sectors have traditionally remained disconnected from each other.
  3. Build the capacity of stakeholders in promoting child rights, child development, and well-being.

The expected symposium outputs are a summary report, newsletter op-ed article, and policy brief developed by the research trainee under Vaghri’s supervision and in collaboration with attendees of the symposium.