Multiple sclerosis likely begins years before the first neurological symptom. During this period, it can present as a set of yet to be well-defined, subtle symptoms, leading patients to increasingly seek medical attention years before actual MS symptom onset, and diagnosis. Our aim is to better understand the earliest signs of MS. We will look for poorly understood signs and symptoms such as sleep disturbances, palpitations, shortness of breath, and skin conditions among others that may appear months or years before MS onset. We will see if these signs are different in men and women and how such differences vary across different age groups. In addition, previous studies suggested that women who developed MS had fewer pregnancies and increased contraceptive use in the five years before MS onset. This may reflect lifestyle changes even before MS onset. We will look at all these issues in more depth than has ever been done before. We will have access to health data from large populations so that we can look in detail at people with and without MS. Our aim is to help doctors and researchers recognize when MS actually starts and to help doctors, patients and families get prompt, appropriate treatment for everyone who develops MS.
Program: Trainee
Team-based postpartum and infant care models: effects on service use, outcomes, and health system costs in the one year after birth
The months following childbirth may be difficult for new parents caring for a new baby (or babies) while recovering from pregnancy and birth. Team-based maternity care draws on the strengths of interprofessional teams (physicians, midwives and allied health) to improve patient care and outcomes and is a current provincial priority in British Columbia (BC). Midwifery care provides frequent post-delivery contacts, at-home care, and on-call support during this critical postpartum period. There is a growing trend in BC towards informal team-based arrangements where midwives support mother-infant dyads after physician-attended birth. In other settings, up to 18% of postpartum individuals and 8% of newborns visited the emergency department in the postpartum 6-week period. We will examine whether interprofessional team-based partnerships in which midwives provide postpartum care is associated with hospital service use (emergency department visits, hospital readmissions), maternal or infant outcomes, and health system costs in British Columbia. Findings will inform knowledge users in health policy and system leadership positions by evaluating this aspect of team-based maternity care applied in the postpartum period.
Mosquito taste receptors for detecting human sweat and initiating blood feeding
The World Health Organization estimates around 725,000 mosquito related deaths a year. This makes mosquitoes one of the deadliest animals on Earth. Mosquitoes bite us humans to get nutrients and pass deadly diseases to us as a consequence. It is well studied that mosquitoes rely on their sense of smell to find us. Yet, what tiggers them to bite us once they land on our skin is unknown. We hypothesize that mosquitoes use their sense of taste to trigger the biting behaviour. In addition, taste receptors on their legs play a crucial role in triggering biting. We will test this by first identifying which receptors will respond to human sweat. This will be done by presenting individual receptors with human sweat and identifying the ones that respond. We will then follow up by removing these receptors from the legs of mosquitoes to see if they will still bite. This will allow us to find the receptors that trigger the biting behaviour in mosquitoes. With this information, we can find safe compounds to deter mosquito biting. We can also design mosquitoes that are bad at biting to be released into the wild to produce offspring that are bad at biting as well. A combination of these methods can protect us from mosquito diseases.
Age-related impacts of the intestinal microbiota on multiple sclerosis: defining mechanisms of neurodegeneration
Progressive Multiple Sclerosis (pMS) is a prevalent neurodegenerative illness in Canada. Unfortunately, people living with pMS have limited treatment options. Age is a strong risk factor for MS progression, indicating that biological changes that occur with age could contribute to pMS-related neurodegeneration. All forms of MS show associations with the microbiome, and the microbiome undergoes substantial changes during aging. However, whether age-related changes to the gut microbiota are important contributors to the neurodegeneration seen in pMS remains undefined. Thus, I will perform fecal microbiota transplant (FMT) of samples collected from healthy aged vs young people into microbiota-depleted mice, followed by treatment to induce a laboratory form of MS. This experimental set-up allows me to isolate the role of an aged vs young microbiota on MS outcomes. In preliminary studies, mice harboring an aged microbiome develop pMS-like disease. I will identify specific microbes and the molecules they produce in aged FMT mice that exacerbate neurodegeneration. These studies will lead to better understanding of the mechanisms driving neurodegeneration in pMS, and the identification of new targets for this treatment-resistant disease.
Harnessing NK cell mechanics for fine-tuning cancer immunotherapy
Cells of the immune system help maintain health and defence against cancer by detecting and killing cancer cells in the human body. Immunotherapy is a cancer treatment strategy that boosts the immune system to fight cancer using native immune cells made in the body. Natural killer (NK) cells are a subpopulation of immune cells. NK cell-based immunotherapy has gained attention for cancer treatment due to the relatively simple procedure, although their low efficacy remains a challenge, despite many breakthroughs. An NK cell has a sophisticated molecular architecture that dynamically changes when interacting with neighbouring and target cells. When NK cells encounter cancer cells, their molecular architecture is changed to enhance their ability to combat cancer. However, details of how this happens are not entirely understood, limiting our ability to engineer them for fighting cancer. I will study the properties of cellular structures under the stimuli of weak or strong immune responses to find the best cellular architecture for cancer immunotherapy. An understanding of structural change during immune response will provide valuable information to devise a novel strategy for cancer treatment.
HIV prevention for underserved men who have sex with men: a community-based mixed methods exploration of access needs and preferences
Oral HIV prevention medications are highly effective and available at no-cost to clinically eligible patients in British Columbia. Men who have sex with men (MSM) remain a key population at a higher risk of HIV infection. However, studies suggest that certain sub-groups of MSM who would benefit from these medications are currently underserved. For example, MSM who identify as bisexual or heterosexual may be especially unlikely to use oral HIV prevention medications, leaving them and their sexual partners at higher HIV risk. Through analysis of community health survey data and one-to-one interviews with MSM in BC, my project will identify barriers to using PrEP among underserved MSM. I will explore their opinions about and preferences for different forms of HIV prevention, including oral and long-acting injectable forms of these medications. My research will help healthcare providers, community organizations and public health bodies to better understand the HIV prevention needs of underserved MSM. It will enable them to reach underserved MSM with information about ideal HIV prevention options, and to improve HIV prevention among this population, reducing the burden of HIV for these men and their partners.
Characterizing the pain needs of structurally vulnerable palliative care patients with substance use disorder
An important part of palliative care is managing pain, including physical, emotional, mental and spiritual suffering. However, people with substance use disorder (SUD), who experience homelessness and poverty (for example), face barriers in having their pain needs met. These unmet needs are due to gaps between palliative and substance use care, and because this group of people face social and health care barriers that limit their access to resources and support. Unmanaged pain among this group can have significant consequences, including suffering at the end of life and increasing risk of negative health outcomes, such as overdose. This study will examine the pain needs of palliative patients with SUD, gaps in the management of pain for this population and develop approaches to meet these needs. Research activities include interviews with palliative care patients with SUD and service providers, observations in care settings, and mapping tools to understand the broader scope of the topic. By making connections between pain management approaches among palliative and substance use health care, this research will generate new ideas to improve the management of pain among palliative care patients with SUD.
Leveraging longitudinal COVID-19 vaccine cohorts to deconstruct SARS-CoV-2-specific adaptive immune responses and the potential for viral infection to induce immune amnesia
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in >400 million documented infections and ~6 million deaths worldwide. Safe and effective vaccines have significantly reduced morbidity and mortality due to COVID-19, but even the newest bivalent vaccines provide only limited protection against infection with current SARS-CoV-2 variants. Further in-depth analyses of immune responses to COVID-19 vaccines and SARS-CoV-2 infection are needed. Moreover, the rise in non-COVID-19 respiratory infections in 2022 has led to speculation that SARS-CoV-2 may impair immune responses to other pathogens. This is plausible since SARS-CoV-2 can dysregulate B cells, the specialized immune cells that produce antibodies, but few studies have examined this. My research will examine the generation of B cell responses against the original (ancestral) SARS-CoV-2 and newer Omicron variants in a diverse cohort of vaccinated adults. I will characterize B cells that cross-react with ancestral and variant Spike, which are likely to help protect against new strains. Finally, I will explore the consequences of SARS-CoV-2 infection on B cell responses to other respiratory viruses.
Defining epigenetic alterations in liver cancer at single cell resolution
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.
Restoration of miR-185 in combination with BCR-ABL downregulation by non-viral delivery of siRNA with lipomeric carriers and lipid nanoparticles sensitizes drug resistant cells to TKIs
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.