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.
     

Novel nanomedicines for resolving inflammation as a treatment for type 2 diabetes

This project proposes a new nanomedicine approach to treat type 2 diabetes (T2D). Studies in humans and mice have shown that inflammation in fat tissues and the pancreas is a major driving force for the development of obesity-induced insulin resistance and diabetes. A major limitation of current drugs is that they distribute over the entire body, exposing all cell types, while only a small amount reaches the desired target cells at disease sites, such as macrophages in inflamed tissues. This results in limited drug efficacy and unwanted side-effects. We aim to develop a new treatment for T2D that exploits the natural physiological processes to suppress inflammation in macrophages within fat tissues and the pancreas with high potency. We will use lipid nanoparticles (LNP), which are drug delivery systems customized to stably carry a large amount of drugs to macrophages.

Scientific development in this project will involve testing of LNP containing immune-modulating drugs in obese, diabetic mice, and measuring the anti-inflammatory and anti-diabetic effects. With close to half a billion people worldwide suffering from T2D, we believe that the proposed cell-specific treatment can have a significant impact on health and the economy.

Developing a safe and effective analgesic for chronic pain relief

About 6 million Canadians report a form of chronic pain, yet half of the sufferers do not get enough pain relief from their medications. This severely affects their quality of life and has significant social and economic burdens. Opioid medications, such as morphine, are the most powerful pain killers available, but these drugs also cause serious side effects, such as suppressed breathing, leading to a high risk of death from overdose.

In 2016, there were 2,861 opioid overdose deaths in Canada, and British Columbia (BC) reported the highest opioid-related death rate, which was three times the national average. The overdose rate in BC increased 17-fold from 2011 to 2016. This worsening opioid epidemic resulted in changes in opioid prescribing standards, and half of the chronic pain sufferers can no longer access opioid drugs in BC. Dr. Li will lead a team to develop a new, effective, and safe drug for chronic pain relief. This new drug will improve pain relief options and access for patients who suffer from chronic pain.

The team will work with companies to ensure this new drug is readily available to pain sufferers through primary care to all populations in BC and the whole of Canada.

Improving cancer immunotherapy using G-CSF-blocking antibodies to overcome myeloid cell-mediated immunosuppression

Half of all Canadians will develop cancer and 1 in 4 will die of the disease. Cancer immunotherapy is a promising solution applicable to multiple types of cancer. The immune system plays a critical role in removing tumour cells. However, tumours escape the immune system to continue growing. Immunotherapy can enhance the immune system's ability to fight cancer and, in some cases, achieve long-lasting remission. However, many cancers do not respond to currently available immunotherapies.

In partnership with ME Therapeutics, we have developed antibodies targeting G-CSF, a protein overproduced by several major cancer types that induces immune suppression and may cause resistance to immunotherapy. Blocking G-CSF reduced the number of colon tumours and normalized immune system function in a mouse model of colon cancer.

We have selected a lead antibody that can successfully bind and inhibit G-CSF both in cell culture and mouse model systems. Our plan is to develop new animal models to test if blocking G-CSF can make resistant tumours sensitive to immunotherapy as well as to evaluate G-CSF in patient tumour tissue. Overcoming treatment resistance will substantially impact primary health care for cancer patients. 

Novel bioengineered probiotics increase colonization and persistence in the gut enhancing bioavailability and their therapeutic potential for inflammatory bowel disease

Inflammatory bowel disease (IBD) is a major global health burden and the rapid surge in pediatric cases in Canada over the past decade is raising alarm bells. Current pharmaceutical therapies are risky or ineffective, cost and health-wise, especially for long-term use and are associated with severe side effects. Therefore, new alternative therapies for IBD are needed urgently. Probiotic therapy, which is the ingestion of non-pathogenic microorganisms to provide health benefits, is considered a potential treatment option. However, clinical trials using probiotics for IBD treatment have yielded very inconsistent and difficult to interpret data.

Specific to IBD, the gut environment is highly inflamed and oxidized; these properties may interfere with the growth and therefore beneficial effects of probiotics. As such, current probiotics are ineffective at persisting in the hostile gut of IBD patients. A novel therapeutic approach is to engineer designer probiotics that strategically target these limitations. The present invention relates to bioavailable and optimized genetically-engineered recombinant probiotic bacteria with enhanced therapeutic potential, for use in treating IBD.

Here we propose that our novel patented next generation microtechnology is an alternative to traditional probiotics to enhance bioavailability and is a potential alternative therapeutic option for IBD. This proposal aims to test how the designer probiotics enrich gut health in pre-clinical
models.

A GlycoCaged drug delivery system to improve the treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) is lifelong, debilitating condition that afflicts one in every 150 Canadians. Worryingly, the number of people diagnosed with IBD is rising worldwide, including among new Canadians and children. There is currently no cure for IBD, so treatment options are limited to managing symptoms with anti-inflammatory drugs.

Unfortunately, the oral administration of classical steroid IBD drugs is complicated by undesired side effects that result from premature uptake in the stomach and small intestine. Dr. Brumer and colleagues have recently developed a novel approach to link anti-inflammatory steroids to a complex carbohydrate from vegetables. This carbohydrate protects the steroids, allowing them to pass to the lower bowel, where they are released by beneficial bacteria of the microbiota.

Dr. Brumer and colleagues have validated this 'GlycoCage Technology' in the laboratory, including preliminary testing with human gut bacteria and in a preclinical animal model of IBD. The next steps in this research include further testing in additional animal models to determine dosage, safety, and efficacy. This will provide essential data before progressing to human trials and clinical application.

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.  

Familial Hypercholesterolemia – Patient Engagement Forum

Co-leads:

  • Liam Brunham 
    University of British Columbia 
  • Fred Hazen
    St. Paul's Hospital

Team Members:

  • Lubormira Cemakova
    BC FH Registry 
  • Dr. Durhane Wong-Rieger
    Canadian Organization for Rare Diseases

Trainee:

  • Dr. Miles Marchand
    University of British Columbia

Familial Hypercholesterol (also called FH) is the most common inherited form of high cholesterol, and affects 1 in 250 British Columbians. FH leads to lifelong elevation in blood cholesterol and up to 10-times increased risk for developing heart disease, which often occurs at a young age. Most patients with FH have not been diagnosed, and may not be receiving appropriate treatment.

Research into FH has advanced rapidly over the past several years, and we now know significantly more about the genetic causes of FH, how to diagnose it, and the best available treatments. Communicating and disseminating the results of this research to patients and their family members are critical to translate these research findings into improvements in care of these patients. The purpose of this proposal is to hold a patient forum on FH which will include lectures from physicians, nurses, dieticians, genetic counsellors and patients, as well as interactive small group sessions.

The goals of the forum are to disseminate research advances to patients with FH and empower patients to become advocates for the community with FH. With this funding we will be able to offer a number of travel grants to support patients from outside Vancouver to attend. 

A socially responsible dentist: an evidence-based curriculum to address stigma and discrimination

Co-leads:

  • Mario Brodani
    University of British Columbia 
  • Kinnon Ross
    Providence Health Care

Trainee:

  • Dr. Abiola Adeniyi
  • Michael Siarkowski
  • Maxine Harjani

Canadians suffering from drug addiction and mental illness experience higher rates of poor oral health than their counterparts. They may also experience stigma and discrimination by dental and dental hygiene providers while accessing much needed dental care services. There has been a call 'to teach cultural diversity' broadly within dental and dental hygiene education to foster practice that is inclusive, sensitive to diversity, socially responsible, and without prejudice.

The project team will:

  1. Include those in the community affected by drug addiction and mental illness to co-develop an evidence-based undergraduate dental curriculum that will inform dental and dental hygiene practices within the University of British Columbia, and
  2. Pilot this curriculum with the incoming class of 2020/21 undergraduate students to aid in skill-set development.

The team will co-develop an interactive curriculum based on a flipped classroom concept in a safe environment focused on educating oral heath care providers who are compassionate, fair, and socially responsible. The central research question is:  'How can we foster an interactive and open dialogue about social responsibility, in a transformative learning environment, when caring for those suffering from mental illness and/or addiction?'  

The above question is broad enough to be transferable to other health care disciplines and this new curriculum will be made available to them.  

No one size fits all for measuring what matters: Supporting the use of PRO data in healthcare

Co-leads:

  • Richard Sawatzky
    Trinity Western University
  • Jae-Yung Kwon International Society for Quality of Life Research, University of British Columbia

Trainee:

  • Ronak Brahmbhatt
    Trinity Western University

Patient reported outcomes (PROs), which allow patients to report on their physical and mental health and wellbeing, are increasingly used in clinical practice and decision making. However, patients may not be consistent in how they interpret and respond to these questions.

Differences in the meaning of PROs across individuals or over time are known as differential item functioning (DIF) and response shift (RS). Ignoring these differences could lead to erroneous healthcare decisions. Although there are statistical methods to adjust for DIF and RS, these are complex to interpret and apply. To address this, our team is developing resources on DIF and RS (introductory video, webinar, and analysis software code).

Building on this prior work, we now propose to facilitate wider uptake of knowledge for interpreting and analyzing PROs by developing a webinar that includes case studies and an online interactive learning module specifically for clinically-oriented audiences (clinicians and decision support analysts).

Expected outcomes include:

  1. Increased awareness of DIF and RS and their implications for clinical practice and decision making, and
  2. increased ability to analyze and interpret PROs data while accounting for DIF and RS.