Michael Smith Health Research BC funds UBC researchers to lead health research and improve patient outcomes

The majority of bacterial infections grow as biofilms: bacteria surrounded by nanoscale structures made of biomolecules such as DNA, sugars, and proteins. Antibiotics often attach to these sticky nano-architectures and fail to reach their bacteria targets, leading to severe antibiotic resistance. Nanoparticles (NPs) can act as tiny drug carriers that protect drugs within NPs until they reach their targets. However, it is unknown how NPs should be designed to travel within biofilms and deliver antibiotics most effectively. This challenge in designing NPs is compounded by a lack of benchtop biofilm models that represent the biofilm nano-architecture found in infections. My lab develops nanoscale materials such as NPs that have directed bacterial interactions to guide them within the biofilm environment and trigger drug release. This will improve drug efficacy and reduce side effects. We are also developing nanomaterials that mimic the natural biofilm architecture to be used as a new biofilm model that will help us develop next generation nano-therapeutics. By using advanced microscopy and mouse models of infection, we will assess and optimize nanomaterial design to improve antibiotic efficacy and treat resistant biofilm infections.

Our bodies contain unique molecular markers that can reveal important information about our health, but analyzing these markers is challenging due to the vast amounts of noisy and complex data. Our research aims to develop new computational tools that make it easier and more cost-effective to interpret these molecular signals, with two main goals: First, we’re creating methods that could be applied to detect cancer earlier through blood tests by detecting fragments of DNA from various organs in the body. Second, we’re studying how environmental factors in early life influence prenatal and long-term health by examining what causes these molecular changes. We will create user-friendly software tools that enable scientists and doctors to analyze molecular data more effectively and affordably. This could lead to better cancer screening tests and help us understand how early-life experiences affect health. We’ll also evaluate how well these tests work in different healthcare settings to ensure they benefit diverse patient populations. Ultimately, our work will advance both cancer detection and our understanding of child development while making cutting-edge molecular analysis more accessible to the research community.

Urban Indigenous people in British Columbia, representing 78% of the province’s Indigenous population, are largely underserved by health research, which often lacks meaningful engagement, limits their agency, and inadequately represents their diverse Nations, cultures, and lived experiences. This five-year program aims to address these gaps by co-developing scalable, culturally responsive health research governance models that center urban Indigenous perspectives. Guided by Indigenous and Community-Based Participatory Research methodologies rooted in relational accountability, respect, and reciprocity, the program will engage urban Indigenous health leaders, community members, and health researchers through surveys, interviews, sharing circles, and workshops to co-create community-informed pathways for health research engagement. These models will inform future research policies and practices, enhancing the relevance of health research for urban Indigenous populations. Ultimately, this will advance the field by embedding Indigenous perspectives into health research, ensuring that health studies better reflect and serve urban Indigenous communities across BC.

In Canada and British Columbia, youth (ages 12-24) struggle to find health care for mental health and substance use concerns, like depression, vaping, and drinking.

In the last ten years, British Columbia has tried to improve access to care for mental health and substance use by launching integrated youth services. These bring together health and social services and providers, such as doctors, nurses, and counselors, that a youth might need in one place. While this might be a promising way to help youth, we do not currently have a lot of research about these services.

The goal of my research is to answer important questions about what impacts these new services are having on youth, communities, and the health care system and how we can improve these services. I will talk to youth, families/caregivers, service providers, and decision makers to hear more about their experiences with these services. I will also compare information, like the number of hospital visits, between youth who access the services and youth who do not access the services. I will work closely with youth, families, service providers, and decision makers so that my research answers the questions that are most important to them..

Cytomegalovirus (CMV) remains one of the most common infections after transplant and despite medical advances, still poses significant challenges. Currently, transplant patients at risk of developing CMV infection are either given antiviral medications or are monitored by blood tests that detect CMV. However, these medications can have serious side effects and may only delay but not eliminate CMV infection. Furthermore, monitoring the blood for CMV ideally requires weekly blood draws.

We are designing a blood test, the CMV-AIM assay, as a personalized approach to monitoring the immune system against CMV after transplant. This test will not require additional blood collections as it will be done concurrently with routine blood tests, and not more frequently than once monthly. We have previously shown in kidney transplant patients that the CMV-AIM assay done early after transplant can predict those patients that later go on to develop CMV infection requiring treatment. The goal of this study is to trial and expand the CMV-AIM assay to all solid organ transplant patients, including lung, heart, liver, and kidney transplant patients and to validate this test in the clinical immunology laboratory to incorporate it into patient care.

Parkinson’s disease (PD) is the fastest growing neurological disorder. A loss of dopamine producing brain cells is thought to cause movement difficulties and various nonmotor symptoms in PD, and the majority of patients are prescribed dopamine replacement therapy (DRT). Although DRT is effective, many patients develop fluctuations in its effects and different patients respond differently to DRT. This research program will use non-invasive imaging to investigate how brain activity changes in real-time after patients with PD take DRT, in terms of “on-target” effects on brain areas associated with symptom improvement and “off-target” effects on uninvolved areas. Magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) recordings, which provide detailed information about the “when” and “where” of brain activity, will be collected at multiple time points alongside measurements of movement and cognitive symptoms while a patient’s normal DRT takes effect. An understanding of how patients’ brains respond to DRT will help develop methods to more precisely determine an appropriate DRT regimen for patients who experience motor and cognitive fluctuations, and guide future research on PD medications and neuromodulation.

One in ten Canadians have kidney disease which can ultimately require treatment with dialysis or kidney transplant or lead to death. Treatment of kidney disease depends on us understanding its cause. Genetic causes of kidney disease, due to changes in people’s genes or DNA, are increasingly recognized as important causes of adult and childhood disease. We do not know how many people in British Columbia have genetic kidney diseases or their impacts on health.

One in eight people with kidney disease do not have a clear explanation for the cause of their kidney disease, termed unexplained kidney disease. We think there are unidentified genetic changes that explain some of these peoples’ kidney disease.

We will look at how many people in British Columbia have genetic kidney diseases based on clinical genetic testing and how genetic kidney diseases impact their health . This will include a few pre-specified groups of people with common genetic conditions. We will then perform whole genome sequencing on people with unexplained kidney disease to try to find new genetic changes that explain why they have developed kidney disease. We expect these findings to improve the health of people living with kidney disease in British Columbia.

Type 2 diabetes (T2D) remission, which means that blood sugar levels return to sub-diabetes levels without taking any glucose-lowering medications, is possible for many people living with T2D through changes to diet/lifestyle. T2D remission can offer new hope to those living with diabetes and empower them to make positive lifestyle changes. Despite this potential, many individuals living with T2D and most importantly, their healthcare providers, remain unaware that remission is possible.

This research project will offer a new and complete approach to help people achieve T2D remission. Using social media, we will find and connect with individuals living with T2D, informing them about how changes in diet and lifestyle can lead to remission. They will then be referred to registered dietitians who have been specially trained in our program’s lifestyle strategies for T2D remission.

This project will greatly benefit health research, the healthcare system, and the overall well-being of individuals living with T2D. By closing a full circle of awareness, specialized healthcare training and personalized expert support, our program will empower people living with T2D to successfully reach and maintain remission.

Indicators of harmful use of non-prescribed addictive substances—reflected in healthcare visits, hospitalizations, and deaths—are rising in Canada, signaling an urgent crisis. Addressing this issue requires a focus on identifying and supporting demographic groups that are disproportionately impacted. One notably vulnerable group is individuals with psychosis, who show alarmingly high rates of substance use disorders (SUD). Substance use relapse in this population is associated with increased hospitalization, incarceration, and a heightened risk of early death due to opioid overdoses, suicide, or infectious and cardiovascular diseases. However, individuals with SUD and psychotic illnesses are often excluded from clinical research, resulting in a lack of evidence to guide best practices for prescribing antipsychotics, SUD treatments, and other psychotropic medications. This project aims to develop guidance by analyzing real-world clinical evaluations, diagnostic data, and prescribing patterns and linking them to outcomes such as substance use relapse, medication side-effects, and healthcare utilization using electronic medical records along post-discharge data from two provincial centers in BC.

Knowledge gap: Diabetes is a leading cause of amputation because it causes nerve damage (numbness, pain), skin wounds (infections), muscle loss (weakness), and bone thinning (fractures, osteoporosis). Acute intermittent hypoxia (AIH, breathing cyclical low & normal oxygen levels x2 hours) promotes healing and treats other diseases of the nervous system. We believe AIH will improve the effects of diabetes on the nerves, skin, muscle, and bone of the leg.

Aim 1 (Rodent Model): we will investigate if AIH treats nerve, skin, muscle, and bone of the diabetic leg. Animals with diabetes treated with AIH will be compared to no-AIH controls using behaviour testing, specialized imaging, and assessment of tissue samples.

Aim 2 (Clinical): we will investigate if AIH improves recovery of sensation, decreases pain and improves wound healing for human patients with diabetes. Fifty patients will be recruited from the multidisciplinary lower limb reconstruction program for inclusion.

Expected Outcomes: Based on preliminary data, we believe AIH is a safe and effective strategy to treat the diabetic leg.

Impact: Without the need for surgery or medications, AIH may provide treatment for diabetic patients to treat pain, infection and amputation.

This research will use advanced DNA sequencing techniques to enhance the way we diagnose and treat infectious diseases. In many serious infections, the cause cannot be identified, and the patient must be treated with broad-spectrum antimicrobials, which can either kill the pathogen and harm the microbiome, or even fail and promote resistance. We will use a novel technique, metagenomic sequencing, to analyze patient samples and identify the exact cause of the infection, including those caused by rare and unknown microorganisms. DNA sequencing will also be used to study these microorganisms in real time and determine the genetic mechanisms by which they cause disease and develop resistance to antimicrobial drugs. Armed with the genetic information of these microorganisms, we will also be able to create new, rapid tests to quickly identify them in patient samples. This research will improve patient care by enabling faster and more accurate diagnosis of infectious diseases, leading to better treatment outcomes and potentially reducing the spread of antimicrobial resistance.

Around one in four Canadians have high blood pressure (BP), also known as hypertension. High BP is a major risk factor stroke, heart attack, and kidney disease. Lowering BP levels by a small amount, can reduce risk of heart disease and stroke. Hypertension control rates in Canada are the lowest that they have been in a decade. Patients with hypertension frequently need to visit the emergency department (ED) due to high BP. Hypertension is one of the chronic diseases that can be managed effectively with digital health technology. We do not know the best way to manage BP after people are discharged from the ED. Many doctors worry that their BP may go too high or low if we treat or do not treat their BP. We do not know if digital health technologies can be used to safely monitor these people as they transition from the hospital to home and help control their BP. We will test to see if home blood pressure telemonitoring (HBPT) plus pharmacist case management will result in better BP control for participants who are discharged from the ED with uncontrolled high BP compared to standard care. We hope to create a toolkit on how to implement a HBPT program for people discharged from the ED with high BP and inform guidelines on high BP.

Persons living with kidney disease may develop imbalances in gut bacteria, which in turn may produce substances (metabolites) that can increase inflammation, worsen health, and increase risk of kidney disease progression. We are conducting a study to assess the types of gut bacteria present in stool samples and types of metabolites in blood samples from people with kidney disease not on dialysis. We will include some people with normal nutritional status and some with a nutrition disorder called ‘protein-energy wasting’ that commonly occurs in kidney disease. This research program will assess the interactions between gut bacteria and metabolites in the blood, how they vary by nutritional status, and how they relate to kidney disease progression.

This work will help us develop personalized treatment strategies to improve nutrition in people with kidney disease, and to prevent progression to kidney failure. Throughout the research process, we have collaborated with 2 patient partners and consulted with the BC Renal Dietitians Committee. We plan to share study findings through publications, webinars and patient educational materials.