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.

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.
     

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.

Developing long-, short-, and near-term dynamic models of risk and resilience for intentional self-harm in BC youth

My research aims to answer two questions: when and under what circumstances do some young people intentionally physically harm themselves, and how can we improve our clinical tools to reduce these behaviours? Intentional self-harm is alarmingly prevalent in young British Columbians: around 5-7% of BC youth have attempted to end their own lives, 10-15% have experienced serious suicidal thoughts, and 15-18% have engaged in non-suicidal self-injury. These behaviours can have devastating impacts on youth, their families, and their communities. Providing care for suicidal youth is among the most stressful tasks that mental health professionals face, due in part to the difficulty of accurately predicting risk.

To address this important health problem, we need to improve knowledge of:

  1. signs of imminent, near-term risk of intentional self-harm, and
  2. dynamic processes of accumulating risk or resilience in vulnerable youth. My research uses linked provincial health records, prospective cohort studies, and smartphone and wearable technologies to study how risk and resilience for intentional self-harm evolve over hours, days, weeks, months, and years. The research will be used to create and improve decision-making and self-monitoring tools that youth, caregivers, and clinicians can use to reduce and prevent self-harm.

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.

HIV pre-exposure prophylaxis implementation to key priority populations across British Columbia: Towards HIV elimination

Co-leads:

Executive sponsor:

  • Mark Gilbert
    BCCDC

What are the barriers and facilitators to optimizing HIV Pre-Exposure Prophylaxis (PrEP) implementation in different geographies and priority populations across BC?

HIV PrEP is now universally covered in BC for those deemed at high risk for HIV; however, there is still sub-optimal uptake and adherence of PrEP for a wide range of reasons, including a lack of understanding of PrEP effectiveness, low perception of HIV risk, lack of awareness, and social stigma.

This project will synthesize available surveillance, administrative, and survey data to provide quarterly reports for different regions to provide crucial information on uptake of PrEP at initiation of program/intervention, changes over time, and trend analyses. For example, data from the BC Centre for Excellence in HIV/AIDS (BCCfE) DTPPrEP database on PrEP program users could be linked to inform PrEP referral and uptake based on risk indicators.

This research could also link to qualitative interviews and focus groups with providers and patients regarding health care, social and other barriers. Social community mapping activities could also be used within different communities/regions to better understand the health care networks and community members’ experience trying to navigate these to access PrEP.

Key outcomes from this project will be supporting health authorities, community groups, health care providers, and patients to use PrEP; and contributing towards HIV elimination.

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. The non-adoption, abandonment, scale-up, spread, and sustainability (NASSS) framework will be app/node/5126lied to several innovative assistive technologies (ATs) currently being developed in British Columbia for older adults.

By using a community-based participatory research methodology, this work will bring researchers, key health system decision-makers, technology developers, care-givers 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 the health system priority of services for seniors with complex medical conditions and the commitment to keeping seniors in their homes as long as safely possible (aging in place). The ATs in this project will be 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.

This research will also contribute to enhancing access to effective primary health care. ATs are a crucial medium for accomplishing this, 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.

This project will work towards directly improving the uptake, spread and sustainability of promising ATs in British Columbia, and will develop and sustain effective partnerships between the research community, the BC Ministry of Health, CanAssist and other relevant organizations.

Positive Living, Positive Homes: The online HIV housing toolkit

Co-leads:

Trainee:

  • Joanna Tulloch
    University of Victoria

Housing is an important structural determinant of health. Positive Living, Positive Homes (PLPH) is a longitudinal, qualitative, community-based research (CBR) study conducted in three British Columbian (BC) communities (Prince George, Kamloops, and Greater Vancouver). PLPH has investigated the complex relationship between housing and health for people living with HIV, and how policies and programs across BC interact with health and wellbeing of PLHIV.

In keeping with the tenets of CBR and the greater/meaningful involvement of people living with HIV/AIDS (GIPA/MIPA) principles, in each site, the team engaged people living with HIV, service providers, and other partners to participate as study team members in study implementation, data analysis, and knowledge translation activities.

Between June 2015 and October 2017, 99 adults living with HIV across the three BC study sites participated in baseline in-depth interviews for PLPH, with follow-up interviews one year later (72 people completed the follow-up interviews). In addition, in-depth, semi-structured interviews were conducted with 42 HIV and/or housing service providers and policy makers working in a range of community and government organizations at the three sites.

A key finding of the study related to the impact of stigma and discrimination across the housing spectrum for people living with HIV. Several participants were denied access to housing upon disclosure of living with HIV. Stigma and discrimination also drove some participants into isolation and away from care and resources related to their health and housing. Given this, the PLPH CBR team recommended that an essential KT tool would be an Online HIV Housing Toolkit that would increase access to housing information for people living with HIV and service providers who support people living with HIV, and ultimately help people living with HIV and service providers better navigate BC’s housing system.

PLPH is led by Dr. Catherine Worthington (Public Health and Social Policy, University of Victoria) and Evin Jones (Pacific AIDS Network (PAN), which holds CIHR HIV/AIDS CBR operating grant funds for the study (2014 – 2018)). PAN is a member-based coalition with almost 50 member organizations responding to HIV, HCV and related issues across BC. PAN is uniquely positioned to develop and host an Online HIV Housing Toolkit because they have developed and hosted many training and online tools for its member agencies and other key provincial partners.