Precision medicine to drive prevention and management strategies for women with endometrial cancer

Endometrial cancer (EC), or cancer of the uterus, is the most common gynecological cancer in Canada, with new cases and deaths increasing annually, due to an increase in the rate of common risk factors, like obesity. In British Columbia, the number of new EC cases is projected to increase by 50% and mortality to double by 2031. We must investigate economically feasible prevention strategies to control the rate of this cancer.

For women diagnosed with EC, it is difficult for clinicians to reliably distinguish between cancers that can be cured and those likely to progress, because parameters currently used to make this judgement are not reliably measured. Consequently, we give toxic treatment (chemotherapy and radiation) to many patients who may only require surgery, and fail to treat others as aggressively as we should.

My research program adopts a precision medicine approach, defined by the individualized care to EC patients, to predict:

  1. which patients are at high risk of developing EC, and
  2. and of those, which patients are likely to progress. Precision medicine can also improve early screening efforts to reduce EC incidence by detecting and treating pre-cancers, promoting early improved diagnosis, and targeting treatment recommendations for EC patients. This will benefit both patients and the healthcare system, as fewer EC patients will be given expensive toxic cancer treatments that are not needed, or to which they are unlikely to respond.

Adapting BC’s healthcare system for equitable and tailored service provision to sexual and gender minorities

Lesbian, gay, bisexual, transgender, and queer (LGBTQ) people face judgment and discrimination on the basis of their sexualities and genders. This leads many LGBTQ people to avoid seeking treatment from the healthcare system, to hide aspects of their sexuality/gender when seeking care, or to selectively visit LGBTQ-affirming providers.

The goal of this research program is to develop a comprehensive understanding of healthcare access patterns among LGBTQ people in BC.

Objectives:

  • To describe points of healthcare access for LGBTQ people (‘where’)
  • To explore LGBTQ people’s reasons for avoidance, concealment, and provider selection when seeking healthcare (‘why’)
  • To characterize the ways in which service providers in BC ensure that their services are LGBTQ-affirming (‘how’)

Administrative health data, surveys, and interviews with providers and LGBTQ people will produce a detailed description of where, why, and how LGBTQ individuals navigate healthcare.

Collaborators include public health clinics, community organizations, and general practitioners. This research will provide recommendations to adapt BC’s healthcare system so that LGBTQ people receive the services they need, when they need them.

Development and Application of Computational Methods for Profiling Cancers at Single Cell Resolution

Cancer is a complex disease with many factors which determine how rapidly cancer cells can grow and spread throughout the body. Significant differences exist within the cancer cell population of a patient. These differences shape the interaction of cancer cells with the surrounding healthy tissue, with dramatic variation between patients. This so called cancer heterogeneity has profound implication for patient prognosis, and is one of the primary challenges to developing effective cancer treatments. Recent technological advances now allow for the measurement of multiple aspects of individual cells within a cancer. This has created an opportunity to precisely characterize the set of mutations in each cancer cell, along with their functional consequences and how they impact interactions with surrounding cells. My group will develop statistical machine learning approaches to analyze the complex datasets generated by these technologies.

Working alongside clinicians and biologists at BC Cancer, part of the Provincial Health Services Authority (BC Cancer), we will apply these computational methods to study the evolution of metastatic breast cancer and the mechanisms of relapse in follicular lymphoma. Ultimately this research will provide important insights that can guide the development of better strategies for the diagnosis and treatment of these cancers.

Exploring novel approaches to reduce the prevalence of depression

Depression has recently become the leading cause of disability, worldwide. It affects one out of every 20 Canadians, causing significant suffering to patients and their families and costing the economy CAD$32.3 billion each year. Previous efforts to address the burden of disease caused by depression have mostly been focused on expanding access to mental health services.

Recent analyses, however, suggest that the prevalence and burden of depression has remained the same in the last two decades, in spite of the intensified efforts to improve access to mental health services. This is mainly because not enough efforts have been spent on providing treatments that are adequate, appropriate, and equitable, and also because of the lack of investments on prevention.

In my research program, I propose to:

  1. study treatment patterns that are adequate and that work for specific group of people at specific times
  2. examine complex combinations of social factors that influence access to mental health services, and
  3. identify community-based activities that promote mental wellness and resilience. The program of research has the potential to generate recommendations at the individual, health system, and community level that can be implemented to reduce the prevalence and burden of depression over time.

Balancing act: Measuring and optimizing the challenge point in rehabilitation to improve walking balance after stroke

Up to 73% of people who are able to walk post-stroke suffer a fall, commonly within the first few months after discharge home. Optimizing the approach to rehabilitation of walking balance remains vital to long-term outcomes post-stroke.  A fall poses a significant risk of injury and erodes confidence. The loss in confidence alone can lead to decreased activity levels, loss of independence and social isolation that affect quality of life and overall health, even hastening death.

After stroke, much of the focus of rehabilitation is on improving balance and walking. However, no objective measures are available to assist clinicians in making important treatment decisions such as walking balance task type or intensity of the challenge.  Unlike retraining of walking endurance that uses established measures such as heart rate to monitor and plan progression of walking endurance, there are no objective measures to guide progression of rehabilitation of walking balance.

To address this issue I am working with clinicians and people with stroke to:

  1. develop clinically useful balance measurement technology for use during rehabilitation;
  2. better understand the interaction between physical ability and confidence during rehabilitation of walking post-stroke; and
  3. incorporate this new technology together with algorithms that model rates of change to personalize the level of challenge of walking interventions and assure the best outcome for each individual with stroke.

Developing new anti-cancer drugs that target abnormal signaling networks in cancer

A defining characteristic of cancer cells is their ability to grow and replicate in an uncontrolled manner. Cancer cells have altered signaling pathways that allow them to bypass checkpoints that would normally prevent their rapid growth. STAT3 protein is a master regulator of cancer cell signaling and is found to be overactive in 70 % of cancers. While healthy cells can survive without STAT3, cancer cells become addicted to overactive STAT3 and are sensitive to disruptions in this pathway.

As a result, several drug-like molecules have been explored for their ability to inhibit STAT3 signaling in cancer cells. While some have shown promising anti-cancer effects, issues with selectivity and toxicity have prevented their clinical use. With the goal of identifying better STAT3 inhibitors, my research program uses cutting-edge techniques to determine how STAT3 inhibitors function in cells. We investigate what exactly the inhibitor binds to inside a cancer cell and how that affects STAT3 signaling. We also use these techniques to develop our own STAT3 inhibitors which we then explore as novel anti-cancer agents. Our ultimate goal is to produce new medicines that can help patients win their battle against cancer.

Implementation of Shared Decision Making to Improve Person- and Family-Centred Care

The healthcare system is undergoing a paradigm shift toward person- and family-centred care. While this is a critical priority, it will be challenging to put into practice. One strategy to implement this change is shared decision-making (SDM), a process that supports patients and providers to discuss the risks and benefits of options, clarify preferences, and make choices based on their informed values. Knowledge translation and implementation science (KT/IS) are key approaches for accelerating this system change.

To advance the science of implementing evidence into policy and practice, I will implement and assess evidence-based SDM tools in routine primary care, focusing on maternal health.

Key objectives include to:

  • Investigate factors contributing to successful implementation of SDM tools in routine care,
  • Adapt, implement, and assess health care professional training to support uptake of SDM,
  • Investigate how documentary film can work as a method of knowledge translation to support patients’ informed choices, and
  • Evaluate partnerships between researchers and policy makers to catalyze the implementation of SDM.

This research will be used to advance person- and family-centred care in maternal health and in primary care more broadly.

Strengthening primary care through population-based research

Primary care includes the day-to-day services provided by family doctors, nurse practitioners, and other health care providers. High quality primary care that follows patients over time and coordinates specialist and hospital care is key to an effective and efficient health care system. Unfortunately, many Canadians struggle to get primary care where and when they need it, despite there being more family doctors per person than ever before.

My research program seeks to answer the following questions:

  1. How can we make sure we have the right number of health care providers to meet the needs of Canadians now and in the future?
  2. How can we efficiently organize delivery of primary care to meet the needs of patients? How do we improve access to effective care for underserved groups, including people managing both mental and physical health conditions and recent immigrants and refugees?

I analyse routinely collected data from health care delivery and look at the impact of policy changes using statistical models. I work in partnership with researchers who have complementary skills collecting information through interviews and focus groups. My research teams include patients, care providers, and people who plan health services.  This helps make sure we ask questions that matter and that research results will help change our health care system.

Effects of cellular origin on the development of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer related deaths mostly due to the absence of symptoms as the cancer develops. This leads to diagnosis after the tumor has already become widely invasive and cannot be surgically removed. Unfortunately, surgical removal of early stage tumors is the most effective treatment option and other treatments, such as chemotherapy, are woefully ineffective.

Thus, there are two major fronts where research could improve the outcomes of pancreatic cancer patients:

  1. early detection and
  2. more effective treatments. Early detection requires knowledge of the events associated with tumor development, while improving treatments requires a thorough understanding of pancreatic cancer. It is clear that a 'one-size-fits-all' strategy has largely been ineffective for pancreatic cancer. We hypothesize that this is partly because PDAC is a 'catch-all' diagnosis for tumors that look the same, but may have different properties due to differences during their development. Our research program seeks to identify these differences and ultimately leverage the differences to improve patient outcomes through the development of personalized treatments.

Identity in mental health: A focus for early intervention and improving social functioning

Personal identity–one's psychological sense of personal continuity–is an important aspect of mental health, informing one's motivations, behaviours, and social relations. Disruptions in identity can contribute to prevalent conditions such as personality disorders. Indeed, distorted identity is a core aspect of personality dysfunction and disorder, contributing to considerable negative health and social outcomes–and a prominent challenge for health care providers and systems. Interventions that strengthen identity during young adulthood may be a potent way to mitigate personality dysfunction, preventing entrenched impairment and setting a course for positive mental health.

This proposal features a novel psychosocial intervention aimed at strengthening identity and reducing personality-related dysfunction among vulnerable young adults–tested in a randomized controlled trial. The intervention is designed for use by non-specialists to maximize transferability and impact on access and quality of care. Building on the applicant's work in maladaptive personality and identity, the project is set within a broader program of research on identity-focused intervention, including within early psychosis and recovery from alcohol misuse.