Characterization of Gli proteins as a novel therapeutic target in prostate and breast cancer.

Prostate (PCa) and breast cancer (BCa) are leading causes of cancer deaths. These tumours depend on sex hormones that function through receptor proteins for their growth. For this reason, hormone therapies inhibiting these receptors are the first approach for controlling metastatic disease. However, hormone therapies eventually fail. Therefore, understanding how receptor proteins promote cancer growth will affect our approach for designing effective treatments for PCa and BCa. 

Recently, we showed that sex hormone receptors activate Gli proteins in PCa and BCa cells. Gli proteins are regulators of genes that control cell growth and overactive Gli proteins cause brain and skin cancers. I propose that hormone-activated Gli is responsible for the growth effects of sex hormones in PCa and BCa. My work will characterize the relationship of sex hormones, Gli proteins and cancer cell growth. In addition, I will employ a novel technique to understand binding of Gli proteins with sex-hormone receptors and develop a new strategy to block cancer cell growth. This project will lead to a breakthrough in our understanding of sex hormone receptor action in PCa and BCa and evaluate a new approach to control the growth of these deadly diseases.

Understanding adaptability in egg-laying behavior in Aedes aegypti

Mosquitoes are the deadliest animals on the planet. Aedes aegypti mosquitoes are found in many parts of the world. When they bite people to take blood, they can transmit microorganisms that cause disease. One reason that Ae. aegypti is so deadly is that it is closely associated with people and can breed in a wide range of water-filled containers such as dumpsites, construction sites, and discarded plastic containers.

Ae. aegypti must carefully choose where to lay their eggs. These decisions are achieved by using different senses to detect water where their progeny can thrive. The aim of my proposal is to characterize the genes and brain circuits important for mosqutioes to identify optimal egg-laying sites. I will perform these studies across groups of Ae. aegypti that have distinct egg-laying preferences to understand how these mosquitoes have adapted to the wide variety of environments associated with people.

Ultimately, my work will help us understand why Ae. aegypti (and not other species of mosquitoes) have become so intertwined with us and, thus, are so deadly. These studies will provide foundational data to support critically important mosquito control efforts around the world.

Determinants of sexual and reproductive health care for im/migrant women: a community-based mixed methods study to realize comprehensive primary care in BC

Primary care is key to a working health care system. Good primary care is based on relationships with a provider who knows a patient over time and sees the whole person in context, so they can address social needs that particularly impact the health of marginalized groups. Although im/migrants are a big part of the population in Canada, they have less access to good primary care. We use ‘im/migrant’ including all people that arrive in Canada from another country, including refugees, economic and undocumented im/migrants. Some groups (refugee claimants, precarious status) have even more limited access to primary care and may face worse health. This is especially true for im/migrant women of reproductive age. An important feature of primary care is sexual and reproductive health (SRH) care, like contraception, cervical cancer screening, and pregnancy care. We can learn about and improve primary care for im/migrant women by looking at their experiences with SRH. Guided by im/migrant women, this project uses interviews and information from the health system to describe their SRH within primary care in BC. This will produce collaborative solutions for SRH in primary care that promote equity for im/migrant women and families in BC.

Feeding patterns, nutrient status, and neurocognitive development in toddlers 18-24 months of age: A Randomised Control Trial

Early childhood represents a critical period in which a child’s brain undergoes rapid brain development and is critical to later health and wellbeing. During this time, infants and young children have especially high needs, both for energy and key essential nutrients, when compared to older children and adults. Yet feeding and nutrition guidelines for infants and toddlers during this crucial developmental window remain poorly understood, explained in part by the major changes with regard to infant and toddler feeding practices in the past century.

Therefore, the specific focus of this project is understanding how feeding patterns (including breastfeeding, cow’s milk, and formula) in the first two years of life are associated with toddler cognitive development at 24 months of age. In particular, the research will focus on key nutrients recently identified as crucial for healthy development and function, but which are currently limited in toddler diets and guidelines. The study has clinical and public health implications for toddler nutrition and will help inform and clarify current toddler feeding guidelines in order to improve the health and development of Canadian children.

Using computational modeling to investigate the cognitive processes underlying behaviors related to gambling disorder in rats

Pathological gambling is an addictive disorder characterized by repeated problematic gambling despite severe negative consequences, often linked to poor decision making and impulsivity. Research into gambling disorders has been facilitated by using rodent tasks that are directly translated from tasks used in humans. Traditional analyses for these tasks result in simplistic measures linked to decision making deficits and impulsive behavior. More recently in clinical research, computational modeling has been applied to data from human tasks to allow more sophisticated, in-depth analysis of the psychological and cognitive processes underlying these behaviors. Despite many parallels in task measures and structure, computational approaches are much less frequently used in the analysis of rodent behavioral data. Using multiple large datasets from rodent gambling and decision making tasks, this project proposes to use computational modeling to investigate the underlying cognitive processes involved in performance on these tasks. This will improve translatability of findings from preclinical research, and enable the generation of testable hypotheses for novel therapeutic/behavioral interventions to address problematic gambling behavior.

Understanding counsellor-client interactions in spinal cord injury exercise counselling: a novel method to explain outcomes of randomized controlled trials by assessing intervention fidelity

Behavioural interventions often consist of conversations between counsellors and clients and can be a successful way to promote a healthy lifestyle. However, controlled intervention outcomes are not always successfully translated to real-world settings. A possible reason for this poor translation, is that researchers do not use information on how counsellors and clients interact with each other to explain intervention outcomes. Recently, a new method, called state space grids, has been developed to study and visualize how a counsellor and client interact with each other over time. This study will use state space grid methods to study conversations about health-enhancing exercise between counsellors and clients with spinal cord injury (SCI) to explain health outcomes. Participants receive tailored exercise counselling. Recordings of the sessions will be analysed using state space grids. The findings will help us to better study and understand how, when and why counselling is successful in changing health behaviour. These new insights can be used to develop training guides for counsellors and improve exercise counselling. In turn, understanding and improving effective exercise counselling will enhance lives of many people with SCI.

Understanding the challenges and opportunities in communicating vaccine risks and benefits to midwifery clients

Studies have shown that vaccinating pregnant mothers protects both mothers and children. Yet, recent surveys suggest that one third of Canadian parents are unsure about vaccinating. Mothers often decide how they feel about vaccines during pregnancy, and healthcare workers play an important role in helping them make these choices. More and more new parents in Canada choose to give birth with the help of a Registered Midwife (RM). Unlike other healthcare providers, RMs, following the guideline of Informed Choice, encourage their clients to make choices for themselves using the best available information. Because of this, some RMs feel that they should not make a strong pro-vaccine recommendation. This research project will focus on creating midwife training resources that are compatible with the model of Informed Choice. Using interviews with midwives, educators, and professional associations, we will develop tools for continuing education adapted to the RM profession. By better understanding the challenges midwives face when talking about vaccines, this study will help RMs enable their clients in BC and Canada to make better informed decisions about vaccination.


End of Award Update: October 2022

Most exciting outputs

Our research aimed to better understand how midwives discuss vaccination in pregnancy (and infancy) with their clientele. Through interviews with midwives and other professionals we learned more about vaccine conversations in pregnancies and some of the related challenges. We published research showing how Informed Choice conversations aimed to inform and empower pregnant people about vaccine decisions and described what changes could be made to better support midwives who discuss vaccination and provide vaccines to their clients.

Impact so far

We have created a vaccine communication training module with the Continuing Professional Development program at UBC, which is available in French and English to midwives across the country. Our team also published results from our interviews in international peer reviewed journals to reach a wide audience.

Potential influence

Hopefully, this research has shed light on how midwives are capable vaccine counsellors, with the training and expertise to engage and inform vaccine hesitant populations.

Next steps

This research is being continued by my colleagues at the Vaccine Evaluation Center at the BC Children’s Hospital Research Institute. Our team is continuing to collect data to develop and test a clinical intervention package that will provide communication tools like pamphlets and informative videos to be used in midwifery clinics in Canada.

Useful links

Identifying Complex Associations between Biomedical HIV Treatment and Prevention Strategies, Condom Use Behaviors, and STIs in Gay, Bisexual, and other Men who have Sex with Men

Across Canada, the rate of sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (gbMSM) has significantly increased. Public health officials have suggested that the increasing STI rates are a result of decreasing condom use, motivated by the utilization of biomedical HIV treatment and prevention strategies (henceforth: biomedical strategies), like Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylais (PEP). However, our understanding of associations between gbMSM’s biomedical strategies, condom use behaviors, and STIs is limited because: 1) research has yet to assess how individual, interpersonal, and social factors shape the relationship between gbMSM’s biomedical strategy choices and condom use, and 2) research has yet to confirm that gbMSM’s biomedical strategies shape condom use choices in ways that actually predict a subsequent STI. My research will address these limitations by analyzing the rich and exciting data of the Engage Study, a four-year long Canadian study of gbMSM’s sexual health and behaviors (see: https://www.engage-men.ca/). This research will inform newer, more effective STI interventions for gbMSM that incorporate sexual health practices of the modern age.

Exploring Altered Cortical Activity Dynamics in Huntington’s Disease

Huntington’s disease (HD) is a fatal inherited neurodegenerative disorder caused by a single gene mutation. Most patients present with disordered cognition and movement in middle age due to striatal and cortical neuron degeneration. However underlying HD processes begin earlier and are incompletely understood. Although striatal projection neurons are most vulnerable, cortical pathology likely primarily drives cognitive dysfunction in HD and may impact striatum health via extensive cortical-striatal projections. Using voltage-sensitive dye imaging, we monitored the activity of cortical neurons in HD-model mice, where we found sensory-evoked signals spread more extensively. This suggests an excitation/inhibition imbalance, the details of which we are clarifying with additional experiments. Ultimately, the above could affect motor and cognitive performance in HD and contribute to neuronal toxicity mediated by excessive excitatory neurotransmission. This research furthers our understanding of early brain circuit changes in HD and how they contribute to neurodegeneration; hopefully these findings will inform future early HD treatment interventions. Results will also be published in scientific journals and communicated to the media.

Effect of Diesel Exhaust on the Respiratory Microbiome in COPD Airways.

Some of the lung bacteria protect the lung against bad germs. Tests have shown that people with sick lungs often do not have these ‘good’ bacteria in their lungs. Our team has shown that breathing air pollution causes the lungs to be irritated, leading to inflammation. Inflammation of the lungs can make it hard to breathe, especially for people who have lung problems. We think that polluted air could change the lungs’ bacteria. To understand this, we asked healthy volunteers and people with lung sickness called chronic obstructive pulmonary disease (COPD) to participate in a study. They sat in a room for 2 hours and breathed either clean air or air with diesel exhaust that is a model of air pollution like that found in big cities around the world (i.e. Mexico City, or New Delhi). A doctor checked them and took small samples of fluid from within their lungs. We will use these samples to examine the lung bacteria and evaluate the effect of these bacteria on lungs’ health. This study will help uncover how air pollution affects our lungs and bacteria that are inside the lung. This study will help doctors and governments make decisions about traffic-related air pollution and respiratory health.