Program: Trainee

Hepatocellular carcinoma (HCC) is the most common liver cancer and is predicted to become the third most prevalent cause of cancer mortality by 2030. Therapeutic options are limited and those that are available have inadequate efficacy. HCC tumors share similarities with developing liver cells and express genes important for liver development. However, the genetic basis of these similarities still remains unclear. Many liver cancers have mutations in genes that regulate chromatin structure, however how chromatin is altered in HCC and how this contributes to abnormal gene expression have yet to be examined. Our study will utilize advanced single-cell genomic methods to identify changes in chromatin structure in HCC tumors and compare them to adjacent liver tissue and normal livers. This will lead to the identification regulatory DNA sequences and their gene targets associated with HCC progression. We will investigate the function of these DNA sequences and their gene targets in the context liver development using a model of human liver development derived from stem cells. Our study will result in a better understand the molecular underpinnings driving HCC and facilitate discovery of improved therapeutic targets.

Over 130,000 people in Canada are living with and are actively being treated for bloodod cancers. The main problem with our available current therapy is their inability to kill blood cancer stem cells that are responsible for drug resistance and cancer relapse. Our lab has found that targeting a novel pathway using gene therapy to restore the activity of miR-185 can significantly impair the growth of blood cancer stem cells and sensitize them to therapy. This study will investigate the combination of targeting several key proteins using miR-185 and targeting BCR-ABL using siRNA in order to effectively eradicate blood cancer stem cells. Importantly this treatment strategy does not show any side effects in normal blood stem cells, providing a therapeutic window to specifically target blood cancer stem cells. This study aims to investigate the therapeutic potential of this gene combination using gold-standard lipid nanoparticle technology and a newly established animal cancer model. We hope this work will provide a proof-of-concept for more effective strategies to overcome drug resistance and improve the outcomes of patients diagnosed with blood cancers.

Chronic obstructive pulmonary disease (COPD) and asthma are two different diseases that affect the airways. Around one-third of COPD and asthma patients have features of both asthma and COPD and thus are diagnostically labeled as asthma-COPD overlap (ACO). ACO patients experience worse symptoms and more serious respiratory attacks than those with COPD or asthma alone, but we do not know why. To address these questions, our study will investigate the underlying inflammatory mechanisms in the airways of patients with ACO. We will collect tissue samples and cells from the airways of volunteers with ACO using a technique called bronchoscopy and perform genomics on these samples. These data will enable us to identify the key airway features of ACO. We will also use this cohort to determine which features of ACO lead to a good therapeutic response from inhaled corticosteroids, a class of medications used in COPD and asthma. We will use high-resolution imaging techniques to investigate how inflammation relates to persistent changes in the structure of the airways and the lungs. Our research will reveal the disease mechanisms of ACO so that we can better diagnose and prescribe the most effective therapies for ACO in clinical practice.

When the blood-contacting materials are applied for specific applications such as hemodialysis, blood transportation and etc., our body will regard them as an “invader”, and quickly activate the coagulation system to “protect” itself. The activation of coagulation will induce thrombosis, resulting in early treatment termination or lead to other complications such as pulmonary embolism. In clinical practice, the use of anticoagulants to temporarily block the coagulation system to perform such medical procedures, however, significant challenge arises as normal hemostasis is impaired in anticoagulant action. Many patients treated with anticoagulants have to be repeatedly hospitalized due to life-threatening bleeding. In fact, there is no material currently available which is truly antithrombotic. Building on a new concept, in this project, we will focus on developing a universal surface modification approach that can be applied to any device to avoid the surface-induced thrombus generation without interfering the normal hemostasis. The benefits of this research are immeasurable, nearly 2.6 million patients worldwide will be benefited from it annually in the field of hemodialysis alone, not to mention the other areas mentioned above.

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting more than 35 million people worldwide. It is an age-dependent progressive disease that doubles mortality, degrades life-quality, and becomes increasingly difficult to treat with time. Therefore, it is essential to find new biological markers that allow early identification of individuals prone to develop AF and to optimize the treatment of the arrhythmia. Recently more than 100 genetic markers which are referred to as single nucleotide polymorphisms (SNPs) have each been associated with a modest increase in the risk of developing AF. Since all of us have several of these risk SNPs the challenge, in which this project aims to engage, is to identify combinations of SNPs that confer a high risk of AF and discover how they affect the function of the heart cells. This will then allow health professionals to use SNP analysis to improve risk prediction and to personalize the treatment of people with AF according to the risk SNPs they carry.

For muscle contractions to occur, electrical signals will travel from the brain to the muscle via a complex process. Two key players involved in this process are the voltage-gated calcium channel (Cav1.1) and ryanodine receptor 1 (RyR1). Cav1.1 senses the electrical signal and triggers opening of RyR1 to release calcium required for muscle contraction. When they malfunction, it can give rise to several muscle diseases, such as congenital myopathies, periodic paralysis, malignant hyperthermia, and central core disease. The proposed project will use advanced imaging techniques to look at three-dimensional structures of these proteins to understand the process of voltage-sensing. The project will also investigate how disease mutations, endogenous modulators, and pharmacological agents change the structure and function of these proteins. These structural and functional insights will help us understand the cause of these muscle diseases and provide a framework for design of novel therapeutics to prevent and treat them.

Approximately two million people in North America are living with lower limb loss, caused predominantly from complications of diabetes, peripheral vascular disease, trauma and cancer. The ability to regenerate an organ varies widely across the animal kingdom; while amphibians can regenerate entire limbs, mammals have largely lost this ability. One exception to this rule is the tip of the finger (or digit tip in mice, the model system studied here). In mammals including humans, the fingertip will regenerate completely and appropriately as long as the base of the nail (or nail bed) is still intact or else lead to scar formation. In this proposal, we will study adult mice to ask why this one small part of the body has retained the capacity to regenerate and what controls the decision to regenerate or to form a scar. Similarities with human fingertip injury responses make our system one of the most clinically relevant models of tissue regeneration in a mammal. My proposed study will explore how the nail bed creates an environment enabling regeneration rather than scar formation, and will identify the soluble signals from the nail bed that communicate with other stem cells that ensures the generation of a new fingertip.

Racialized (e.g., Chinese, South Asian) newcomer (e.g., arrived in Canada within 5 years) families experience greater challenges accessing healthcare services for their children with medical complexity (MC). This contributes to unmet healthcare needs and higher rates of hospitalizations, emergency department visits, and readmissions. Yet despite this, there is very little research on the healthcare experiences of racialized newcomer families. In order to learn about these experiences, we will look at organizational- and provincial-level policies to see if they address the needs of these families. We will interview caregivers and have them complete diary entries about their experiences over time. Using what we learn from this research, we will co-develop recommendations with families that address their unique needs. We will share the results with policy-makers, clinicians, and other knowledge users to help improve healthcare services for racialized newcomer children with MC and their families.

Patients have heart transplant surgery as a life-saving measure after heart failure, and it is crucial to minimize unwanted postoperative outcomes. One of the major negative outcomes following heart transplant surgery is acute rejection, which is currently managed with strong immunosuppression treatment. However, this treatment can lead to other unwanted side effects, such as kidney problems and cancer, experienced by 50% and 30% of patients, respectively. To address this problem, I will analyze biomarkers, or biological molecules found in the blood that can be measured to indicate the various negative outcomes after heart transplantation.
Our research group has measured biomarkers in blood extensively and to build on that work, I will use statistical and machine learning analysis techniques to find the biomarkers that could predict and potentially diagnose complications after heart transplant surgery. Achieving this goal will help develop personalized immunosuppression treatments for patients to reduce adverse health outcomes and improve overall patient care after heart transplantation.

Telemedicine became an integral part of health services delivery during the COVID pandemic for Canada and will likely remain so thereafter due to potential for improving access and patient satisfaction.

However, telemedicine likely has its limits. Telemedicine may not be suitable for all cases. Telemedicine can mainly provide visual and verbal information, and some medical conditions and complaints require additional forms of information. Using telemedicine for inappropriate medical conditions or complaints may undermine the technical quality of care.

Drawing on administrative data, this project seeks to examine the kinds of medical conditions and complaints associated with worse quality of care on telemedicine, if continuity of care mitigates such adverse impact, and if such negative impact is distributed inequitably. The findings has implications for policymakers, health care organization leaders, providers, and medical educators regarding how to best adjust the relevant policies and practices so that telemedicine can be used most appropriately.