Research Location: University of British Columbia

High throughput fabrication and characterization of a novel lipid nanoparticle library

My research in optimizing lipid nanoparticle formulations and developing next-generation drug delivery platforms is advancing translational health innovation in British Columbia. By integrating polymer and peptide-functionalized nanoparticles for extrahepatic delivery, and by establishing automated, scalable formulation platforms, my work accelerates the development of more effective and commercially relevant therapies. Through collaborations with both academic and industry partners, these efforts strengthen BC’s capacity for cutting-edge nanomedicine research, foster interdisciplinary training, and contribute to a vibrant ecosystem for health innovation in the province.

 

My research in lipid nanoparticle optimization and functionalized drug delivery systems directly addresses pressing health priorities in British Columbia by enabling safer, more effective, and targeted therapies for conditions that are difficult to treat, including cancer and systemic diseases requiring extrahepatic delivery. By integrating automated formulation platforms and fostering academic–industry collaboration, my work accelerates translational research, enhances BC’s capacity for innovative therapeutics, and strengthens the province’s leadership in developing scalable, next-generation health technologies.

A super-resolution platform for in situ molecular analysis of receptor co-localization mediated by co-stimulatory trispecific antibodies

Trispecific T cell-engager (TriTCE) antibodies are an emerging class of therapeutics designed to enhance the body’s ability to fight cancer by targeting three distinct sites. Bispecific TCE antibodies, which target two binding sites, have been developed and clinically approved for treating various types of cancer. These antibodies typically work by binding to both a tumor antigen and the T cell receptor (CD3), thus activating T cells and redirecting cytotoxicity towards cancer cells. However, their effectiveness relies on having a high baseline of T cell infiltration in the tumor microenvironment. This poses a challenge for treating solid tumors that are poorly infiltrated by T cells and rapidly growing, as the bispecific antibodies may not adequately inhibit their growth.

 

To overcome this limitation, co-stimulatory TriTCE antibodies have been developed. These antibodies not only target a tumor antigen and CD3, but also stimulate a second co-stimulatory T cell signal, known as CD28, which has been shown to enhance T cell activation. This trispecific design has demonstrated enhanced cytokine production and sustained T cell proliferation, leading to improved cytotoxicity against tumor cells. However, the precise mechanism by which TriTCE antibodies bring together the tumor cell antigen, CD3, and CD28 to enhance co-stimulation remains poorly understood.

 

Super-resolution microscopy offers a powerful tool to visualize and understand protein interactions within cells. Fluorescent imaging enables the direct visualization of the three key targets: the tumor cell antigen, CD3, and CD28. However, traditional fluorescence imaging does not have the resolution to visualize these interactions. With the ability to achieve up to 20nm resolution, super-resolution microscopy can directly image and distinguish the organization of the immune synapse by co-engagement of the tumor cell antigen, CD3, and CD28. Super-resolution microscopy will enable us to observe how TriTCEs organize their targets in the intact cell.

 

Our project aims to utilize super-resolution microscopy to gain insights into the mechanism of action of TriTCEs. The intern will play a crucial role in integrating super-resolution microscopy with research on TriTCEs. The intern will learn to apply super-resolution microscopy for therapeutic applications and learn to work in an industrial setting. The intern will utilize STED, dSTORM super resolution microscopes, as well as conventional fluorescence microscopy. The intern will optimize labeling parameters, such as antibody concentrations and microscope settings, to identify optimal imaging conditions. Additionally, the intern will present qualitative visualizations and quantitative measures for the interaction of TriTCEs and develop new analysis paradigms for assessing and quantifying receptor-target interactions.

 

Through this work, we aim to better understand how these antibodies organize their targets, ultimately contributing to our understanding of how co-stimulatory TriTCEs function. Implementing super resolution imaging technology will lead to the development of an analysis platform to provide in situ molecular analysis of the efficacy of current and future trispecific antibody therapeutics under development at Zymeworks Inc.

Identifying and functionally characterizing transcriptional drivers of esophageal cancer progression for nucleic acid-based therapeutic development

Esophageal cancer, a cancer of poor prognosis, arises as either squamous or adenomatous forms, bearing many hallmarks of their tissue of origin. Esophageal squamous cell carcinoma (ESCC) originates from squamous epithelial cells, whereas esophageal adenocarcinoma (EAC) arises from the columnar cells of a precancerous lesion known as Barrett’s Esophagus (BE) following the development of low grade dysplasia (LGD) and subsequent high grade dysplasia (HGD). Furthering our understanding of the biological processes that drive the emergence of these distinct variants will be critical to develop novel targeted therapies and improve outcomes for esophageal cancer patients.

One important biological aspect of cancer progression is the role of nuclear proteins known as transcription factors (TFs). TFs act as master regulators of cellular function and communication by determining which genes a given cell should utilize, activate, or deactivate. In ESCC and EAC, squamous cell (in ESCC) or columnar cell (in EAC) -associated TFs often become aberrantly activated, indicating that divergent programs of gene activation occur in these cancer variants. Furthermore, the overarching cancer-promoting programs engaged by these TFs and their associates, as well as their mechanisms of cancer facilitation through downstream target activation, remain to be full elucidated. Identifying the divergent TF-driven programs activated in these cancers and their consequential impacts on oncogenesis and metastasis could lead to the development of new therapeutic interventions for esophageal cancer patients.

In this project, we aim to identify and characterize the functional impact of the transcriptional programs that drive esophageal cancer progression, with the goal of improving our understanding of the disease’s biology and providing critical insights that could guide innovative therapeutic targeting of oncoproteins.

The proposed project has two primary aims:

Aim 1: Identify functionally relevant TFs driving progression of esophageal cancer variants
To identify functionally relevant TFs that drive ESCC and EAC progression, we will develop and employ a functional DNA barcode-based high-throughput reporter assay to identify TFs that are differentially activated across various esophageal cancer cells and conditions. We will complement this with comparative bioinformatics analysis of ESCC and EAC genomic datasets to identify TFs with differential DNA-binding and regulatory activity between the two cancer types. This integrative approach will enable us to pinpoint key transcriptional regulators specific to ESCC and EAC and shed light on their distinct molecular drivers.

Aim 2: Investigate the downstream targetable gene expression programs regulated by candidate TFs identified in aim 1
To understand how the transcription factors identified in Aim 1 contribute to either ESCC or EAC progression including through the stages of LGD and HGD, it is crucial to elucidate the downstream gene expression programs that they regulate. This aim will focus on mapping the transcriptional and genomic targets of these TFs to determine their functional relevance to esophageal cancer. To do this, we will perform CRISPR gene knockouts of candidate TFs and perform subsequent RNA-sequencing on the wildtype cells compared to knockout cells, to examine genes differentially expressed. By characterizing and contrasting these downstream pathways between esophageal cancer variants, we can identify new molecular mechanisms that drive EAC or ESCC and discover additional therapeutic targets.

During the internship, the MITACS fellow will develop a diverse set of skills and competencies that will support them as a researcher and enhance their professional development. The fellow will further develop their technical proficiencies in advanced molecular and cellular biology techniques, such as RNA sequencing, high-throughput screening methods such as massively parallel reporter assays, and ultimately CRISPR gene editing. Through this internship, the fellow will also advance their project management skills, as they learn to coordinate their research activities between academic and industry settings, set timelines, and manage deliverables. They will also enhance their critical thinking and problem-solving abilities through troubleshooting experiments and interpreting complex data sets. Furthermore, they will have the opportunity to build their professional network within both the academic and industry circles, as well as improve their communication skills through presentations and collaborative discussions with diverse groups. Overall, this opportunity will enable the fellow to develop a comprehensive skill set that integrates academic research with real-world applications.

This project will support Promirin Therapeutics Ltd’s mission of developing targeted cancer therapeutics. By identifying TFs that drive the progression of esophageal cancer, as well as their downstream targets, the research will lead to a better understanding of the disease at a molecular level. This project will help establish the knowledge based required for Promirin to apply their targeted nucleic-acid based inhibitory technology in the context of this cancer type. Lastly, the project will support the Promirin’s broader goals of promoting innovative research and improving patient outcomes.

Development of single-chain antibodies against avian influenza H5N1 for environmental and diagnostic applications

The avian influenza virus H5N1 is shed in infected birds’ saliva, mucous, and feces. Still, other infected animals may shed bird flu viruses in respiratory secretions and other body fluids (e.g., cow milk). The virus can spread rapidly through poultry flocks and among wild birds. Thus, developing diagnostic tests to identify the virus at early stages before dissemination is crucial to contain a pandemic at early stages. 

 

Detecting pathogens during a pandemic has mainly been based on PCR amplification. Although PCR is relatively fast, samples must undergo a lengthy extraction process, especially for environmental samples. Sequential sequencing also requires highly trained personnel, expensive equipment, and specialized facilities. Thus, the current project will develop a rapid test for the surveillance of H5N1 in human communities, point-of-care settings, animal farms, water supply, sediments of wetlands, farming- and human-derived sewages, animal processing plant sewage, and personnel working in animal husbandry. 

 

The project will take place in BC. The project will develop engineered antibodies against the virus H5N1. These antibodies will be used to generate a rapid test. Samples from different environments, such as water supply, sediments of wetlands, farming- and human-derived sewages, animal processing plant sewage, etc., will be sampled, analyzed, and validated by the BCCDC using PCR techniques. The impact of the rapid test will be a fast delivery across the province for the early detection of the H5N1 virus to contain the dissemination and allow better management of the disease.  

The University of British Columbia Genes, Cells and Circuits (UBC-GC2) platform for next-generation multiscale brain research

Brain dysfunction – which impairs both physical and mental health – is one of the greatest challenges to individual and societal well-being today. There is an urgent need for research that deepens our understanding of human brain function, and to use this knowledge to accelerate therapeutic breakthroughs. The University of British Columbia Genes, Cells, and Circuits (UBC-GC2) Platform will address this challenge by uniquely integrating cutting-edge microscopy and gene-expression technologies, enhancing brain research across distinct experimental settings. Led by Dr. Mark Cembrowski and a team of researchers at UBC with support by expert personnel, UBC-GC2 will establish a pipeline that combines functional mapping of cellular-resolution neuronal activity with static data-rich snapshots of neural circuits, cell types, and constituent molecules. Key infrastructure components of UBC-GC2 will include a Two-Photon Imaging Foundry for microscopy to record cellular activity at wide fields of view, and a Cleared Tissue Processing and Imaging Suite with microscopy and genomics equipment for high-sensitivity examination of brain tissue. The UBC-GC2 platform will enable groundbreaking experimental paradigms across a variety of brain disorders and diseases, applied in both living human brain tissue as well as in vivo and ex vivo analyses of rodent models. UBC-GC2 is a BC-based project, but our research deliverables will be available to local, national and international researchers, facilitated by a variety of remote access options as well as an in-person “Collaborative Residency” program. Consistent with our commitment to Open Science, UBC-GC2 will provide freely accessible data, results, analysis methods, and technological advances to the neuroscience community. With cutting-edge technology, expert personnel, and an integrated and open approach, UBC-GC2 holds immense potential to advance fundamental neuroscience knowledge and drive breakthroughs in the discovery and development of next-generation therapeutics.

This project is supported by the Brain Canada Foundation, via an innovative arrangement between the Government of Canada (through Health Canada) and Brain Canada Foundation, and is further supported by the Djavad Mowafaghian Centre for Brain Health and the UBC School of Biomedical Engineering.

Platform for Regulatory Science, Innovation, and Equitable Health Systems (PRISm)

Canada’s life sciences sector is poised to turn research into health solutions for addressing health threats. There is a central challenge: existing practices, policies, and processes slow patient access to new technologies.

 

With support from Genome BC’s Immunoengineering Strategic Initiatives (GISI) and Health Research BC, a new initiative aims to change that.

 

The Platform for Regulatory Science, Innovation, and Equitable Health Systems (PRISm) will position British Columbia—and Canada—as a global leader in regulatory science. By engaging communities and tapping into BC’s robust data ecosystem, PRISm will make sure that new health discoveries reach patients sooner.

 

Led by Dr. Dean Regier, Director, Academy of Translational Medicine, University of British Columbia and Senior Scientist at BC Cancer, PRISm brings together scientists from different fields to collaborate in an innovative way, driving systems change. This research will:

1. Simplify data capture and access, finding new ways to share crucial information across health systems.

2. Fast track product development, producing clinical, economic, and equity evidence that makes downstream healthcare decisions easier.

3. Quickly transition innovations to the market and to health systems, focusing on equity, safety, value, and sustainability.

4. Mentor students and new researchers, building the next generation of experts.

 

Community engagement is central to PRISm. Together, we will ensure that the evidence we produce responds to the needs of diverse populations. Collaborations with governments and industry will make our research findings policy-relevant and immediately actionable.

 

Through inclusive research, training, and decision-making, PRISm will help build a learning health system for Canada—one that is equitable, evidence-driven, and resilient in the face of health threats.

“DeCIDE” – short for “Designer Cellular Immuno-Engineering for Infectious Disease Elimination”

The Zandstra and Levings research groups are excited to receive matching funds from Health Research BC to support our Immunoengineering Strategic Initiative from Genome BC. This funding will support our vision to incorporate cell-based immunotherapies into British Columbia’s pandemic response preparedness.

 

This project is led by Dr. Peter Zandstra, director of the School of Biomedical Engineering at UBC, and Dr. Megan Levings, Investigator and Lead, Childhood Diseases Theme, BC Children’s Hospital. We are pleased to collaborate with Amgen, BioCanRx, Breakthrough T1D, CCRM, and CIHR on this exciting study.

 

The COVID-19 pandemic highlights the need to complement vaccine development with cell therapies. For the clinically extremely vulnerable (~200,000 people in BC), the risk of viral infection is a daily reality. Among people living with a transplant, mortality approached 20% early in the pandemic, and many (>50%) are unable to mount good antibody responses even after receiving two-dose vaccination. Other immune suppressed individuals and older adults also have poor vaccine responses. Poor viral control can also trigger new diseases, such as long COVID, multiple sclerosis, and Lupus, all characterized by inflammation and tissue damage.

 

Our vision is to harness advances in stem cell biology, genome engineering, and biomanufacturing to produce modular immune cell therapies that can be delivered quickly anywhere in Canada. Such “off-the-shelf” cell therapies will: 1) have immediate applications for immune-compromised people and those at-risk of, or experiencing, severe infection-related complications; and 2) be poised to be rapidly pivoted to pandemic response.

Microbiota for Pandemic Interventions and Exploration (MiPEx)

This project is supported by the Genome BC Immunoengineering Strategic Initiative (GISI), with funding from Genome Canada and matching funds through Health Research BC. It is a BC-based initiative with national and international collaborations. 

 

Dr. Carolina Tropini, the BC Principal Investigator from the University of British Columbia, leads a multidisciplinary team alongside co-leaders Dr. Bruce Vallance and Dr. Lisa Osborne. Together, they are tackling a serious health threat: antimicrobial resistance (AMR). AMR makes infections harder to treat and is expected to cause 10 million deaths per year globally by 2050. Many of these infections begin in the gut, where harmful bacteria can thrive when the body’s natural defences are weak. 

 

The MiPEx project focuses on strengthening those defences by harnessing the human gut microbiota—the collection of helpful microbes that live in our digestive system. Some people naturally carry beneficial microbes that help fight off harmful bacteria. This research aims to identify and develop those helpful microbes into “live biotherapeutics,” a new kind of treatment that uses good bacteria to block infections. 

 

The team will use advanced lab techniques and models that mimic the human gut, including gut-on-a-chip technology and germ-free mice, to test how well these microbes work. In the future, this approach could help protect vulnerable individuals, reduce the need for antibiotics, and strengthen Canada’s preparedness for future pandemics. 

 

By developing innovative, sustainable treatments, MiPEx contributes to BC’s health care and biotechnology sectors and supports healthier outcomes for all Canadians. 

 

Canada’s Immuno-Engineering and Biomanufacturing Hub: Engineering Immunity for Pandemic Responses

Overview

Canada’s Immuno-Engineering and Biomanufacturing Hub (CIEBH) is bringing together a coalition of partners to accelerate the development and manufacturing of lifesaving medicines for BC and Canada. Led by the University of British Columbia (UBC), CIEBH is one of five national research hubs established through the integrated Canada Biomedical Research Fund (CBRF) and Biosciences Research Infrastructure Fund (BRIF) competition.  

CIEBH is pursuing an integrated program of biomedical research and talent development, along with building associated infrastructure to support the development and manufacturing of medical treatments in BC and Canada. The Hub will be a strategic partner that facilitates connections between industry, academia, governments and healthcare institutions.  

 

Vision & Mission

CIEBH’s vision is to make Canada a global epicentre for developing next-generation immune-based therapeutics that can be rapidly produced domestically, using the latest innovations in biomanufacturing, in response to future pandemics and other health threats.
 

Our mission is to harness the collective research and training excellence of our multidisciplinary, multisectoral partners to greatly increase Canadian capacity to translate scientific discoveries into patient-ready treatments at rapid speed — saving more lives, sooner.
 

The Hub’s activities are focused on three key areas:
 

  • Increasing specialized infrastructure for applied biomedical research, including wet lab space, core technology platforms, early-stage biomanufacturing infrastructure, and clinical trials infrastructure; 
  • Supporting training and development of skilled talent for the biomanufacturing and life sciences ecosystem; and 
  • Accelerating translation of promising research into commercially viable products and processes.

For more information, please visit immunoengineeringhub.ca or contact CIEBH’s Executive Director, Dr. Michelle Wong at immunoengineering.hub@ubc.ca.   

Screening for youth violence and future victimization risk, a community clinic based randomized controlled trial

Violence against youth is a major cause of death in this age. Youth who have been victims of violence are more likely to be hurt by someone else again. Much of the research in preventing violent injuries in youth have focused on schools and community programs. This research study aims to see if we can prevent youth (age 12-17 years old) from being victims of violence by focusing on general pediatrician clinics. The research team will randomly allot youth to either receive their standard care or to also receive violence screening in their pediatrician appointment. We will then track the youth for the next year to see if they have had any injuries compatible with violence.  

 

This project is jointly funded by a IMPaCT Health Research BC Training Award. This is a British Columbia based project. The Principle Investigator is Dr. Tanjot Singh, a pediatrician and early career researcher.