Cancer is a disease of the genome that disrupt the cells’ key functions and make them grow uncontrollably. DNA sequencing projects have led us to discover that cancer cells involve many genetic changes and that even in a single tumour, there are often multiple cancer cell populations that each carry their own mutations.
Understanding this collection of mutations is important because we need to select therapies that kill all of the cancer cells, not just some of them. Unfortunately, existing computer programs for analyzing “normal” human genome data generated by genome sequencing technologies are limited in scope because they cannot fully characterize all the mutations present in the individual cells of a tumour tissue.
Ideally, researchers would like to monitor how the genomes of cancer cells mutate over time, and how cancer cells travel through the blood stream or the urinary tract and colonize other tissues, forming metastatic tumours. The new liquid biopsy technology has made it possible to capture tumour DNA circulating in the blood stream and to sequence it, however analyzing such data and identifying the spectrum of mutations in an individual patient will require new mathematical and computational approaches.
Brain disorders are among the most significant health problems of modern day with enormous medical, social and economic burdens in British Columbia, Canada and globally. There is a substantial gap between the burden of brain disorders and the resources available to treat them. Neurodevelopmental disorders are particularly devastating, placing a heavy emotional and economic burden on children and their families. A major challenge in tackling these disorders is the inability to obtain and study brain cells directly. New technologies which allow stem cells to be transformed into brain cells are starting to help overcome this hurdle.
By studying brain cells derived from human stem cells, Dr. Pouladi aims to
- understand how brain disorders develop and
- to identify new ways to treat them. A major focus of his studies are monogenic neurological disorders and in particular fragile X syndrome (FXS). FXS is the most common inherited form of intellectual disability and remains without effective treatments options.
The stem cell-based discovery platform established and knowledge gained as part of Dr. Pouladi's program have the potential to advance therapeutic development for not only FXS, but also other neurodevelopmental disorders.
Cells in our body are constantly engaged in physical interactions. They stick together, squeeze through each other, and each possesses a primitive sense of touch. These physical interactions are crucial in processes that control how we grew from a single cell into a complex organism and how they function. In diseases from cancer to neurodegeneration to chronic inflammation, these mechanical regulatory mechanisms are interrupted or impaired, causing cells to lose control and wreak havoc in our body.
The research proposed here aims to understand the changes to mechanical interactions in diseases down to the molecular scale. To do so, we need to develop tiny molecular tools that will allow us to look at these mechanical interactions through a microscope and control them with drugs.
We will build these tools using the latest DNA nanotechnology, which gives us predictable control over the shape and function of these molecules. We will apply these tools to understand how cancer metastasize to a new place in the body and how neurons break connections in neurodegeneration. This will help us identify drug targets towards a cure to two major diseases with high impact to the health of people in our society.
By 2040, 25% of Canadians will have osteoarthritis (OA), a disabling joint disease. This number will be as high as 50% for those who hurt their knee playing youth sport. Currently, the treatment of youth sport knee injuries focuses on return to sport. Few seek care beyond their injury, and little effort is made to prevent OA. Stop OsteoARthritis (SOAR) is a new physiotherapy program to reduce the risk of OA after a youth sport knee injury.
Designed with a team of patients, clinicians and researchers, SOAR teaches active youth how to manage their OA risk, and improve knee muscle strength and physical activity levels after injury. SOAR consists of a knee camp, personalized exercises, wrist-worn activity-tracker and weekly counselling.
This research will assess what youth with a sport knee injury think about SOAR and how well SOAR works to reduce muscle weakness and inactivity – proven risk factors for knee OA. We will also explore new ways to monitor knee health after injury.
The SOAR team will continue to include patient and clinician partners to make sure that SOAR is practical, and relevant. It is expected that SOAR will improve the health of young British Columbians who have a sport knee injury and reduce their risk for OA.
Acutely ill patients often require life-saving measures including breathing tubes and breathing machines (mechanical ventilation; MV). As our population ages and more people have chronic, complex health conditions, MV is becoming a more common, necessary practice.
Despite medical advances, about 2 out of every 3 adult patients experience swallowing problems (dysphagia) following prolonged MV (>48 hours). Untreated dysphagia decreases quality of life, prolongs hospital stays, and leads to complications such as pneumonia and even death. Early dysphagia identification is key to avoid negative outcomes and high healthcare costs. There is currently no scientifically confirmed way to screen for dysphagia in this population.
To address this gap, my research program will study swallowing in patients following prolonged MV using modern methods, such as airway imaging and tests of breathing, tongue strength and saliva. The results will be combined with patient priorities and other evidence to develop better dysphagia detection methods and personalized treatment approaches.
Ultimately, this will lead to the first scientifically supported screening tool for this population resulting in better health outcomes and reduced care costs.
Over 80% of patients who are treated in the intensive care unit (ICU) for a life-threatening illness face reduced physical health, emotional wellbeing and quality of life. Up to half of patients discharged from the ICU are readmitted to hospital within a year with complex medical conditions. This is a tremendous cost of cure for survivors and their family caregivers. Services for patients with complex medical conditions and/or frail patients is a BC Health System Priority.
This research aims to identify patient- and family-perspectives for designing healthcare services that meet their needs. The primary study will involve interviewing ICU patient survivors, their family members and healthcare providers to map the causes of hospital readmission.
These results will inform the design of services to reduce hospital readmissions. The results of these studies will be shared with national and international researchers and clinicians to benefit patients across Canada.
My career goal is to improve the health and quality of life of older Canadians through applying innovative health economic methods to lifestyle interventions among older adults at risk of falls as well as cognitive and functional decline. I propose a multi-disciplinary research program that advances health economic methods for clinical research studies.
Theme 1 of my research program will advance health economic evaluation methodology by answering the question: “Can artificial intelligence combat current methods limitations of economic evaluation?”
Theme 2 will utilize patient outcomes assessed by patients to explore how patient perspectives may optimize adherence to lifestyle interventions to promote quality of life and maintenance of functional dependence. Hence, I plan to advance methods for clinically applied economic evaluation and explore the utility of patient reported outcome measures to efficiently improve health related quality of life.
These methods advancements will provide a new prototypes useful for
- clinical trials with concurrent economic evaluations and
- patient reported outcome measures that promote adherence and resultantly, health related quality of life — ultimately helping older adults “age in place”.
Our goal is to use smartphones and artificial intelligence to improve pain management for children having surgery. This is needed because many children still have a lot of pain even a year after surgery. The pain affects their daily life, and might cause them to return to hospital. A child’s pain is affected by many things, like their biological sex, anxiety, coping skills, pain level, and type of surgery. Importantly, some of these can be altered.
We will collect data to identify patterns that predict which children
- do well after surgery, so we can learn from them or
- do not do well/have significant pain, so we can help sooner or even prevent it. We will involve families and children having surgery now, to collect data for a pain risk score to help future children.
We will design a tool to share pain risk data with families and doctors and test these tools in children coming to hospital for spine, tonsil or dental surgery. We hope that using these tools (pain prediction models) will improve the child’s individual care. Identifying children at high pain risk will allow us to intervene before their surgery. This will lead to quicker recovery, less time in hospital, and less chance of addiction to painkillers (opioids).
The trajectories of people's lives are often shaped by things that fall outside of their control, having more to do with unearned disadvantages than with their own behaviours or biology. Despite solid evidence and practical policy solutions, systematic differences in health and health outcomes persist both within and between countries. Evidence shows the distribution of power, resources, and wealth along social gradients are causes of these inequities. Many people working in health and health research, and particularly in public and global health, describe their work as reducing health inequities or advancing health equity; but research shows their efforts are often poorly aligned the evidence, focusing on symptoms and not causes.
This program of knowledge translation science supports researchers, students, and professionals in different settings (e.g., rural communities, municipalities, health systems) to align their equity intentions with evidence about causes of health inequities. By supporting people to integrate evidence-informed strategies and principles, efforts to improve population health can move toward more productive health equity action that focuses on addressing the causes, rather than symptoms, of inequities.
Marginalized cisgender (cis) and transgender (trans) women experience high levels of gender-based violence, defined as violence perpetrated against someone based on their gender, gender expression, gender identity or perceived gender, as well as multiple forms of stigma. With the overarching aim to optimize trauma- and violence-informed approaches to enhance access to sexual and reproductive care and HIV prevention and treatment, this research program aims to work closely with marginalized cis and trans women to:
AIM 1. Launch a program of research that will i) develop an evidence base to describe complex relationships between and mechanisms linking gender-based violence and multiple forms of stigma with sexual and reproductive health access, and access to HIV treatment and care; and ii) develop innovative metrics, methodologies and tools to advance an understanding of gender-based violence and stigma and trauma- and violence informed care and practice;
AIM 2. Create a research and training platform to develop and inform innovative community-based interventions tailored for and with marginalized women to inform program and policy interventions.
