Rural, remote and marginalized people in areas of suboptimal healthcare service delivery are at increased risk of poor health outcomes during and after pregnancy, such as high blood pressure. Eating nutritious foods during pregnancy has been recognized to support healthy development of the baby, but less is known about the impact on the health of mothers, especially after childbirth. This gap limits the ability to make evidence-based recommendations and contributes to a lower prioritization of mothers’ well-being.
The proposed research seeks to answer the following research questions:
1. What is the current evidence on the impact of nutrition on women’s health during and after pregnancy?
2. Is there a relationship between maternal diets with imbalanced nutrients in sub-Saharan African countries and developing high blood pressure between 20-34 weeks of pregnancy, after 34 weeks, and/or after childbirth?
3. What strategies can be co-designed with community partners to strengthen maternal nutrition and health capacities of vulnerable pregnant populations?
Findings aim to support maternal interventions to support gender equity and reduce health inequities for rural, remote and marginalized populations in Canada and globally.
Program: Trainee
Use of CAR Tregs to induce transplantation tolerance
Organ transplantation, the primary treatment for organ failure, necessitates lifelong immunosuppressive therapy. Traditional immunosuppressants like steroids pose risks of severe infections and cancer due to their non-specific action. To address this, we’ve developed engineered Tregs, which migrate specifically to transplanted organs and prevent rejection. Initial studies in mice demonstrate promising delay in skin graft rejection. However, the effectiveness of Tregs combined with various immunosuppressive drugs used in transplantation remains unclear. My research aims to bridge this gap by investigating how engineered Tregs interact with common drugs to identify optimal combination therapies for transplant tolerance induction. I will also explore the underlying mechanisms of immune suppression. Ultimately, this work will inform the design of clinical trials, optimizing drug-Treg combinations as a therapeutic approach to combat transplant rejection.
AI-based Platform for Ovarian Cancer Biomarker Discovery and Refinement
Ovarian cancer ranks fifth in cancer deaths among women. The revolution in our understanding of genetic and molecular drivers of other cancers has resulted in major improvements in how such cancers are routinely managed. However, standard clinical management of ovarian cancer have not seen any improvements. Significant clinical implications have been achieved by the classification of ovarian cancer based on genetic markers. Pathologists achieve a cornerstone in cancer diagnosis and prognostication by studying the visual microscopic study of diseased tissue (histology). Histology reveals wealth visual information of disease biology about the aggregation effect of genetic alterations on cancer cells. In this project, we plan to produce automated AI-based differential diagnostic tool for major ovarian cancer subtypes, and moreover, investigate the relationship between genetic markers, histology and disease outcome. We then combine these kinds of data for a comprehensive profile of each tumor. New knowledge generated from this project will shed light on the link between histology and genetic markers and identify potential biomarkers that can be rapidly and accurately tested to stratify ovarian cancer for accurate treatment selection.
Using unbiased whole brain methods to understand how impact direction affects the neuropathology of traumatic brain injury in mice
Traumatic Brain Injury (TBI) is a leading cause of death and disability worldwide and often caused by falls, motor vehicle accidents, sports, and violence. Most TBIs are mild (concussion-like) and involve head motion in one or more planes. Although many clinical studies show that complex rotational head motion is associated with worse outcomes, the underlying reasons are unknown. My project aims to fill this gap by determining how head motion during impact relates to changes in levels of injury blood biomarkers and brain pathology in mice. Using our established non-surgical TBI model called CHIMERA (to imitate human TBI), I will deliver impact to the back or side of the head, and measure how the head moves during these impacts using high-speed cameras. I will use cutting edge tissue clearing method to examine brain in 3D and map changes in neuronal activity, axonal and vascular integrity. I will test how these impacts lead to changes in blood biomarkers using clinically relevant tests. Overall, this study will help us understand how impact biomechanics relates to TBI outcomes, which is tremendously important for the future design of helmets and other safety equipment, sport coaching, and concussion rehabilitation.
A chemical biology approach to uncovering modulators of a Parkinson’s disease-linked protein
Enzymes are biological machines which facilitate crucial processes in the human body. A reduction in the function of a given enzyme, sometimes brought about by an alteration or “mutation” to the underlying genetic code, often results in disease. In Parkinson’s disease (PD), a mutation in the GBA1 gene can cause earlier disease onset and rapid motor decline. Furthermore, the enzyme glucocerebrosidase (GCase) that is encoded by GBA1 is less active in PD patients regardless of whether they have a defective GBA1 gene. We hypothesize that GCase is altered or “modulated” by other proteins within the cell. My first goal in this project will be to create improved ways to measure the activity of GCase in live human cells. Previous work has shown that “ratiometric fluorescence sensors” – small molecules which light up when processed by a target enzyme – have high efficacy towards this end. The activity of a large library of existing drug candidates will then be tested for their ability to modulate GCase. Changes measured in GCase activity within cells treated with these drug candidates will help identify these aforementioned unknown “modulators”, thus revealing new insights into the mechanisms of PD and opening new therapeutic approaches.
Impact of COVID-19 pandemic on health care services for hepatitis B
The COVID-19 pandemic led to disruptions in health services. However, impacts of the pandemic on testing and treatment for hepatitis B (HBV) are not well understood, including impacts over the longer term and impacts for people who inject drugs and immigrants from regions where HBV is more common.
This study will investigate the impact of the COVID-19 pandemic and related policies on testing and treatment for HBV from April 2020 to December 2022 in BC. We will look at impacts for the full population of BC and by sex, age, prenatal status, substance use / injection drug use status, and immigration status. We will engage with research users throughout the research process, including immigrant service agency S.U.C.C.E.S.S. and the BC Hepatitis Network.
We anticipate that HBV testing and treatment were reduced in 2020, 2021, and 2022, and impacts were greater among people who inject drugs and immigrants.
The study findings will inform health services and policy related to meeting Canada’s commitment to eliminate HBV as a public health threat by 2030, delivering HBV-related health services during future health system disruptions such as pandemics, and addressing health equity.
Elucidating how the Sotos Syndrome gene NSD1 controls gene expression during neuronal differentiation.
Each cell has the same genetic information, our DNA. Yet, our body consists of many different cell types (eg. muscle cells, brain cells, etc). To become a specific cell type, our cells have the ability to turn genes in our DNA on or off. This selective control of genes is achieved via “epigenetics”, which means on top (epi-) of our genes (genetics). Epigenetics involves chemical changes to proteins that organize our DNA, which are called histones. Changes to histones are made by epigenetic enzymes. When epigenetic enzymes are defective the wrong changes are made to histones. In turn, the wrong genes are turned on or off, leading to disease. An example of such a disease is Sotos Syndrome, a neurodevelopmental disorder caused by a defect in the epigenetic enzyme NSD1. Exactly how defective NSD1 leads to misguided control of genes is unknown. To examine this, I will use gene editing and delete NSD1 in neuronal precursor cells. Next, I will study the effect of defective NSD1 on histone changes and identify which genes are wrongfully turned on or off in these cells. The results from this study will show how defective NSD1 leads to misguided gene control and can help identify new options for the treatment of Sotos Syndrome.
Development of mutation-robust vaccines and antibodies, and their implications for the evolution of SARS-CoV-2
COVID-19 has caused over 774 million cases and 7.02 million deaths worldwide as of February, 2024. The causative RNA virus, SARS-CoV-2, has the ability to rapidly mutate genetically, and these mutations allow it to swiftly infect with increased efficacy and/or severity. These mutations are of concern because they allow SARS-CoV-2 to evade not only antibodies formed by natural infection or vaccines, but also recombinant antibody therapeutics. With new variants emerging roughly every other month, it will not be long before the current repertoire of antibodies and vaccines against SARS-CoV-2 becomes obsolete. Although it is difficult to predict the mutations in the next variant, it is possible with current technologies to examine potential mutations and the activity of such mutated variants. In this proposal, we will test the robustness of mutation-tolerant de novo vaccines and antibodies against SARS-CoV-2. We also seek to understand how SARS-CoV-2 evolves over time and to decipher the mechanism of antigenic escape from diverse antibodies. This platform can guide us in the design of better therapeutics to combat current and future variants of SARS-CoV-2, and other viruses.
Enhancing Canada’s Capacity to Respond to Complex One Health Issues Through Communications and Collaboration
A holistic, collaborative approach that addresses the interconnections of human, animal, and environmental health (‘One Health’) is increasingly recognized as necessary for the management of ongoing and emerging health threats. This requires effective knowledge sharing and communication strategies between government agencies and One Health practitioners (e.g., physicians, veterinarians, and environmental scientists). Using a community-engaged approach, we will describe the scope of One Health issues in two Canadian provinces – British Columbia and Ontario – and review how One Health information is currently shared. Through engagement with a diverse community of stakeholders in academia, government, and practice, we will assess information and policy needs, priorities, and possibilities within local contexts and explore how One Health Communication strategies can be deployed and sustained at a regional level. By combining One Health systems science and communications research, this project will improve our ability and capacity to provide relevant and timely information related to human, animal, and environmental health and mitigate emerging health threats in Canada.
Engagement and citizenship in long-term care: An exploration of resident and family councils
Resident and family councils refer to groups within long-term care (LTC) homes composed of residents and/or family members who meet on a regular basis to discuss matters of concern. In B.C., LTC residents and their family members have the right to participate in these councils, providing a potential avenue to influence decision-making. However, little is known about these councils, how they work, and whether they enable residents and families to influence change.
My postdoctoral research aims to address this knowledge gap through a qualitative study exploring how LTC councils work, how they engage residents and families in decision-making, and the broader contexts in which they operate. First, we will analyze the legal frameworks governing resident and family councils across Canada and compare how they define councils and the specific rights they afford. To explore how councils operate in practice, we will conduct ethnographic fieldwork in two LTC homes. Researchers will observe council meetings and conduct in-depth interviews with residents, family members and staff. Findings from the study will be used to create user-friendly resources highlighting promising approaches and policy recommendations.