Nineteen postdoctoral fellows recognized with health research training program

Is fuel flexibility the key to making better stem cell-derived insulin secreting beta cells for type 1 diabetes therapy?

Pancreatic β cells produce insulin to control blood glucose. Loss of β cells results in type 1 diabetes (T1D), a chronic disease affecting ~56000 BC residents. One potentially curative therapy is transplantation of stem cell-derived (SC) β cells. Insulin is secreted from β cells in response to multiple nutrients, primarily glucose, but also amino acids and fats. Mature human β cells effectively switch between fats and glucose as fuels. SCβ cells do not properly activate this switch, resulting in a failure to secrete insulin in response to glucose. This project compares fat composition, storage, and use in β cells from stem cells and adult human donors and will provide critical understanding of how SCβ cells work and identify ways to improve their function. My preliminary work found a missing factor in SCβ cells with a potential role in fuel use and insulin secretion. I will be part of a collaborative setting at the Centre of Excellence (CoE) for Diabetes Research at UBC, receiving mentorship studying SCβ cells, donor islets, and lipid signalling. The CoE will also support the rapid mobilization of my findings towards transplantation trials and dissemination of results to the keenly interested and involved public affected by T1D.

Extracellular Vesicle–Mediated Mechanisms and Therapeutic Targeting in Viral Myocarditis

Viral myocarditis is an inflammatory heart disease that can lead to heart failure or sudden death, especially in children and young adults. It currently has no approved treatments. This project investigates tiny particles called extracellular vesicles (EVs), which are released by infected heart cells and can spread viral material while triggering harmful inflammation. We aim to understand how these EVs contribute to heart injury and immune responses, and to develop a novel therapy using engineered EVs to deliver a specialized drug directly to heart cells. This drug targets the harmful EVs while the engineered EVs support heart repair. This approach could reduce heart damage, improve recovery, and provide a new treatment strategy for viral myocarditis and other inflammatory heart conditions.

Brain-based prediction of dying duration after life support withdrawal

Organ donation can only occur after death is confirmed. However, when life-support is withdrawn in potential organ donors, doctors often cannot predict how long it will take for the person to pass away. If death takes too long, organs may not stay healthy enough for donation and donation may not be possible because there are strict time limits for when organs can be used. Doctors currently rely on their experience and limited predictive tools to estimate this timing, which can be stressful for families and may lead to fewer successful organ donations.

This project will collect medical information, such as blood tests that show brain injury and signs of increased pressure in the brain from potential organ donors after life-support is stopped. We will use this information to build a low risk predictive tool that helps doctors better estimate how long the dying process may take.

Improving dying predictions will support families, help doctors make confident decisions and increase the number of healthy organs available for transplant. We will share this knowledge with Canadian organ donation organizations and front-line doctors to strengthen donation practices across the country and world-wide.

Elucidating and manipulating the role of the Unfolded Protein Response (UPR) to improve outcomes of stem cell-derived pancreatic islet transplants

Diabetes is a metabolic disorder characterized by the inability of patients to manage blood glucose levels because of insufficient insulin production. Insulin is secreted by Beta cells localized to islets in the pancreas. Injection of insulin is required to manage diabetes in some patients, requiring frequent blood glucose monitoring. Regenerative medicine approaches are being developed as an alternative in which pancreatic islets are transplanted into patients to restore autonomous insulin secretion. Stem cell-derived pancreatic islets (SC islets) have the potential to provide an unlimited supply of islets for transplantation. My research aims to improve SC islet transplants by improving our ability to generate SC islets in the lab and their longevity after transplantation. I will develop tools to study cellular pathways that allow cells to manage high secretion levels and perform studies to better understand the role of these pathways in generating SC islets and their survival. I will then use these findings to inform strategies to improve SC islet generation and longevity. The increased accessibility and success of SC islet transplants will drastically improve the health and quality of life of patients seeking these treatments.

Decoding cis-regulatory logic in Kaposiform Lymphangiomatosis to target NRAS-driven pathogenic endothelium

Kaposiform Lymphangiomatosis (KLA) is a rare, life-threatening disease where abnormal lymphatic vessels grow throughout the body, causing bleeding disorders and fluid buildup around the heart and lungs. KLA is caused by a single genetic mistake in a small fraction of blood vessel cells. Current treatments can slow the disease but cannot cure it, leaving patients dependent on medications for life.

I aim to develop a gene therapy that finds and fixes only the cells carrying this genetic error while leaving healthy cells untouched. My approach combines three targeting layers: custom-designed genetic switches that turn on only in diseased cells, delivery particles that specifically seek out KLA cells, and a gene editor that corrects the typo. I will use artificial intelligence to design these genetic switches, test which cell surface markers can guide delivery particles to the right cells, and optimize the gene editor to fix the mutation safely.

This research will provide a one-time cure for KLA patients instead of lifelong treatment. The platform will also be adapted for other diseases caused by genetic errors in scattered cells, including certain cancers and other vascular disorders.

Applying a comparative effectiveness framework to evaluate perinatal outcomes of biosimilar versus originator biologic disease-modifying antirheumatic drugs

Managing rheumatic disease during pregnancy is challenging. Biosimilar medications, which are lower-cost versions of biologic drugs, have been shown in early studies to work as well and be as safe as the original versions. However, little is known about their effects on pregnancy outcomes. This study will examine how often biologic originators and biosimilars are used before and during pregnancy, and whether women continue or stop these treatments. I will then compare the risks of complications in mothers and babies between those using biosimilars and those using biologic originators. To do this, I will analyze provincial health data in British Columbia, including the perinatal registry of births and other health system records. The findings will provide much-needed up-to-date evidence on the safety of these medications in pregnancy, help guide treatment decisions for women planning families, and support cost-effective prescribing. Results will be translated to diverse knowledge through manuscripts, conference presentations, and patient-engaged outputs (lay summaries, visuals, presentations to the Arthritis Patient Research Advisory Board).

Co-creating mental health care from the ground up with autistic, AuDHD, and ADHD women

Masking involves social mimicry and emotional suppression, which autistic, AuDHD and ADHD (A3) women engage in higher levels due to societal expectations that place greater pressure on them to conform to social norms. This results in misdiagnosis, late autism diagnosis, ineffective treatment, and negative mental health impacts. As such, this study aims to develop educational resources for mental health care providers and A3 women. Research questions are: (1) What are A3 women’s experiences with mental health care? (2) What are their recommendations? (3) How can this inform a new therapy modality for A3 women? (4) How can this be translated into resources for clinicians and A3 women? Applying a critical grounded theory methodology, research activities include interviews with A3 women, online content analysis, and textual analysis of current therapy modalities. KT includes the development of a modular therapy guide for clinicians and online resources for A3 women. Anticipated outcomes are a specialized evidence-based therapy modality, training for clinicians, and resources for A3 women. Potential impacts include increased awareness of A3 women’s experiences and mental health care that meets their needs.

Clinical stratification of de novo metastatic prostate cancer by multi-region aggregate molecular features.

Prostate cancer is the most common cancer in men in Canada, with over 4000 new cases per year. Eight percent of patients are diagnosed with disease that has already spread to other organs. This ‘de novo’ metastatic prostate cancer (mPCa) is highly aggressive and ultimately lethal. While there are several life-prolonging treatments, patient outcomes can be variable despite similar clinical presentation. Evidence from other PCa settings suggest patient outcomes are strongly influenced by the molecular features of their disease, but these features have not been assessed in de novo mPCa.  To address this critical knowledge gap, I have assembled diagnostic tumor biopsy samples and blood samples from 488 British Columbians with de novo mPCa. I will use clinically-practical experimental techniques paired with cutting-edge computational approaches to stratify patients according to the specific molecular characteristics of their tumor. I will intersect these results with clinical data to understand relationships between cancer features and treatment response or resistance. Overall, this study will provide a blueprint for new precision diagnostics and tailored treatment strategies for Canadian men with aggressive prostate cancer.

Design and Development of Novel Molecular Beacons for High-Precision T-Cell-Targeted mRNA and saRNA Delivery

Lipid nanoparticles (LNPs) are delivery vehicles approved for nucleic acid delivery, notably mRNA, as used in COVID vaccines. Although mRNA is a potent therapeutic, LNPs accumulate in the liver, limiting mRNA from broader clinical applications. To direct LNPs to other areas in the body, cell-specific antibodies (proteins created by our immune systems) may be attached to the LNP surface in a process called active targeting. However, the chemistry and fabrication process used for active targeting is inconsistent and difficult to manufacture, resulting in variable treatment efficacy. 
To improve the consistency of active targeting LNPs, we propose a solution that leverages "click" chemistry, a process where two complementary components selectively bind to each other. First, a cell-specific antibody is administered to bind to the diseased cell to act as a beacon, followed by LNPs that click to the beacon. This process will ensure consistent antibody function, improving its targeting efficiency for more reliable LNPs. This work will broaden our understanding of how antibodies and LNPs interact with cells, allowing us to broaden the clinical applications of mRNA to fight cancers, autoimmune diseases, and other hard-to-treat conditions.

Building an Evaluation Framework to Monitor Indigenous-Specific Anti-Racism in BC’s Health System

Indigenous Peoples in BC continue to experience racism in the health system, which has a negative effect health, creates unsafe care, and leads to preventable illness and death. Currently, many parts of the health system are trying to address Indigenous-specific racism, but right now there is no way to clearly see whether these efforts are actually working. Without a way to measure progress, systems can claim change without being accountable for outcomes.

This project will build practical tools to monitor how Indigenous-specific anti-racism work is making real change. First, we will map how anti-racism work is currently being evaluated across BC’s health system. Then, we will work with Indigenous and settler leaders to define what meaningful progress should look like. Finally, we will create an evaluation framework and performance management tool that can track progress of ISAR initiatives at the individual, team, and/or organizational levels.

By the end of the project, we aim to have system-wide tool(s) that can help us know where change is happening, where resistance remains, and what steps are needed to move closer to the eradication of Indigenous-specific racism in BC’s health system.

Understanding how African, Caribbean, and Black families experience and conceptualize early childhood sleep in Canada: a mixed-methods study

Canada’s Black population continues to grow, especially in terms of families with children. Early childhood is a critical period to establish healthy practices that support positive long-term wellbeing. Early childhood sleep, an essential building block in childhood growth and development, has received increasing attention in recent years. However, African, Caribbean, and Black (ACB) communities are not well represented in this research area. In response, my project will map out what we know of early childhood sleep among ACB communities globally; survey ACB families to describe their experiences and practices related to early childhood sleep in Canada; explore how ACB families make sense of early childhood sleep health, especially as it relates to social, cultural, and structural factors that shape early childhood sleep practices and experiences; and voice ACB families’ priorities for early childhood sleep support. This project will help identify ACB families’ strengths and areas of needed support and enrich health professionals’ understanding of how ACB families navigate early childhood sleep in Canada. Findings will also inform how we can better support early childhood sleep health for ACB children in Canada.

Neuromuscular barriers to successful functional recovery after nerve transfer surgery in spinal cord injury

Spinal cord injury (SCI) causes severe muscle paralysis, significantly affecting daily activities, work, and participation in hobbies and sports. Nerve transfer surgery offers a promising treatment for SCI individuals, where a surgeon connects a healthy donor nerve to the injured nerve, with the goal of restoring nerve supply to paralyzed muscles While this surgery is now performed worldwide and has the potential to transform lives, there is limited understanding of its mechanisms. This knowledge gap makes it challenging to explain why some patients experience substantial improvements while others do not. Consequently, this makes it difficult for doctors to counsel patients about the expected results from surgery. Additionally, poor understanding of factors that lead to the return of muscle strength makes it difficult to know how to deliver rehabilitation after surgery. Our research team will use advanced nerve and muscle testing devices alongside specialized software to investigate how nerve transfer surgery works and uncover the factors influencing recovery. This information will be critical to improving doctor and patient decision-making regarding surgery and will greatly improve the quality of rehabilitation after surgery.

Preventing vaccine-preventable diseases among immunocompromised children in Canada – Optimizing dose schedules

Children with cancer or children with diseases (such as autoimmune conditions) that require long-term immune suppressing medications are less able to fight against infections. They may not respond well to vaccines. Thus, vaccine schedules usually recommend extra doses to improve protection. However, we do not know how often these children go to hospital for diseases that vaccines can prevent, or how those illnesses affect them, compared with healthy children. Also, we have minimal information on how much these extra vaccine doses improve protection.

In this project, we will use already collected data to study immunocompromised children admitted to hospitals across Canada with vaccine-preventable infections. We will examine their symptoms and outcomes, and severity of disease in relation to vaccine schedules.

We will work closely with doctors and nurses to make sure our research reflects real clinical needs. We will share our findings in easy-to-understand formats so families, health-care providers and policy makers can use the results.

Findings will improve understanding of vaccine preventable diseases in this group. This information will enable us to identify the best vaccination schedules for these very vulnerable children.

Frontline goblet cells: cellular drivers of barrier dysfunction in ulcerative colitis

Ulcerative colitis is a chronic, incurable inflammatory disease of the colon that can lead to lasting tissue damage, requiring surgery to remove damaged colon. A key source of damage in ulcerative colitis is failure of the protective mucus layer that normally shields the colonic lining. When the protective mucus is compromised, noxious substances in the feces can damage the lining, triggering or worsening inflammation.

In the digestive tract, mucus is produced by specialized cells called goblet cells. There are several subtypes of goblet cells, each of which has a distinct role, making it difficult to identify which population is most important for barrier failure in ulcerative colitis. This project will study intercrypt goblet cells (icGC), which sits on the lining surface where it meets the feces. I found that people with ulcerative colitis have fewer of these cells, which coincides with the presence of inflammation.

This study will determine if the loss of icGC causes mucus barrier collapse in ulcerative colitis,  and identify the factors that cause icGC to be lost or to recover. The work aims to find measurable signs of mucus failure and to point toward ways to protect the mucus layer and reduce intestinal inflammation.

Assessing capacity for admission into involuntary care for people who use drugs: An ethical analysis in British Columbia

Background: In 2025, the BC government began expanding involuntary treatment for people who use drugs. Although involuntary treatment has long existed under the BC Mental Health Act, there is no formal research that reports on how physicians decide patients need involuntary treatment and there is limited guidance given to physicians on performing these assessments. 

Objective: There are 3 aims: 1) To describe policy and guidelines for physicians on determining if patients need involuntary treatment; 2) Examine how physicians interpret and implement these guidelines; and 3) Provide recommendations for improving these processes.
Methods: For aim 1, we will review all policies relevant to admitting patients for involuntary care. For aim 2, we will interview ~20 physicians to see how they determine which patients need to be involuntarily admitted when presenting with signs of addiction. For aim 3, we will use results to generate recommendations to guide future assessments.

Knowledge Mobilization (KM) will include publications, presentations, and educational resources for practitioners. In providing this in-depth examination, we will generate critical evidence and resources to guide practice and policy that supports patient autonomy.

Engineering human immune organoids to study next-generation Treg transplant therapies

Organ transplant patients need strong, lifelong medications to prevent their immune systems from rejecting the new organ, but these drugs can cause serious health problems. To find safer alternatives, this project aims to develop lab-grown human lymph nodes (called organoids) to better understand how the human immune system responds to transplanted tissue. We will use these organoids to study how the immune system reacts to transplant signals and to test a promising new "living medicine" cell therapy called CAR Tregs. CAR Tregs are engineered immune cells that can help protect transplants by calming down harmful immune responses. By studying how these cells interact with other immune cells in the organoids, we aim to discover better ways to prevent rejection without heavy medication. This research could also lead to new treatments for autoimmune and other immune-related diseases.

Adherence to Opioid Agonist Treatment in the Era of Fentanyl

Toxic drug poisoning continues to be a leading cause of death in BC. Fentanyl, a powerful synthetic opioid, is present in most opioids purchased on the unregulated market and has made the drug supply far more unpredictable and dangerous. At the same time, medications such as methadone, buprenorphine-naloxone, and slow-release oral morphine, which are given to help prevent withdrawal symptoms and reduce cravings, remain the most effective medical treatment for people with opioid use disorder. This is referred to as opioid agonist treatment (OAT). People who are engaged with OAT are known to have better health and social outcomes.

However, many people stop OAT early. It may be that as fentanyl in the drug supply has become stronger, people have developed high tolerances, making it harder for current OAT medications to meet their needs. This might lead someone to resort to supplementing with other drugs, exposing themself to potentially harmful, toxic ones. My research will examine whether the changing strength of fentanyl in the unregulated drug supply affects how long people stay on OAT. Findings could help improve how OAT doses are set and support the use of drug supply monitoring in clinical and policy decisions.

Bile Acid Malabsorption as a Driver of Epithelial Barrier Dysfunction in Crohn’s Disease

Crohn’s disease (CD) is a lifelong intestinal inflammatory disease, with a rapidly increasing prevalence. A common but often overlooked complication of CD is chronic diarrhea, which is frequently caused by a condition called bile acid malabsorption (BAM), affecting nearly half of CD patients. BAM-associated diarrhea greatly reduces quality of life, limits daily activities, increases healthcare costs, and is associated with a higher risk of gastrointestinal cancers. Unfortunately, current treatments often fail to relieve symptoms. This, in part reflects the uncertainty regarding where and how excess bile acids, chemicals that build up in BAM, damage the cells lining the intestine. This project will use human intestinal tissue-derived models, to examine how intestinal cells and bacteria respond to bile acids buildup in the intestine, identify mechanisms of injury, and test strategies to repair the gut lining. Findings will be shared through scientific publications, conferences, and collaborations with clinicians, patient organizations, and industry partners. This research aims to define how BAs damage the intestine during BAM, as well as guide better treatments, and ultimately improve quality of life for people living with CD.

Evaluating the Role and Therapeutic Value of MAP1B in Prostate Cancer

Prostate cancer (PCa) is commonly treated by blocking male hormone signaling through suppression of testosterone production or blocking its binding to its main cellular receptor. While these treatments initially suppress disease progression, the cancer often develops resistance and recurs. In about 20% of cases, the disease returns as an aggressive and lethal form known as neuroendocrine prostate cancer (NEPC), which is associated with a median survival of under one year. There is an urgent need to define the mechanisms driving treatment resistance and NEPC progression. Our lab has identified a protein, MAP1B, that is upregulated in response to treatment stress and is highly expressed in NEPC. Suppressing MAP1B expression reduced cancer cell growth, decreased cell movement, and led to a loss of neuroendocrine-like features, suggesting that MAP1B may play a critical role in treatment resistance and NEPC progression. We plan to investigate how MAP1B is upregulated following treatment stress and how it promotes NEPC progression. We will also assess whether suppressing MAP1B slows NEPC tumor growth in an animal model. With these studies, we aim to uncover a biomarker for treatment-induced NEPC and a therapeutic target in advanced PCa.