About 3,000 Canadians receive a diagnosis of ovarian cancer (OC) each year. Despite initial good responses to treatment, the chance of long-term survival is low with ~30 percent of patients living five years from diagnosis. Drugs called PARP inhibitors improve survival but only in about half of patients. Small clinical trials have shown promising results using chemotherapy-free PARP inhibitor targeted drug combinations. This proposed research asks several important questions:
- Do chemotherapy-free targeted treatments work in OC and which drug combinations are best?
- Which order treatments should be given, before or after chemotherapy?
- What are the features of OCs that do not respond to PARP inhibitors and can we find new targets?
We will use samples from two groups of patients to conduct the research: from a clinical trial called NEOCATS and from OC patients that did not respond to PARP inhibitors given as standard of care in BC Cancer sites. NEOCATS trial will run across Canada and is led by BC scientists. Laboratory studies will take place in our Vancouver labs and will use novel mice models to study how OC responds to different treatment combinations. Patient partners with lived experience of OC will help guide the project.
Patients with vitiligo experience social stigmatization due to white patches on their face and hands. The existing therapies have limited effectiveness. Our lab recently discovered that an omega-3 essential fatty-acid derivative, maresin 1, has the ability to prevent development of vitiligo patches. In this proposal, I plan to test its effectiveness and long-term safety using a mouse model of vitiligo. We will induce vitiligo in B6 mice, and then treat them with maresin 1 injections three times a week for 80 weeks, which is equivalent to 60 years of human life, and observe the mice for changes in white patches and development of side effects. We expect maresin 1 treatment to shrink the white patches without causing cancers or other side effects. The experiments will be performed by an experienced research associate, Dr. Mingwan Su, and a graduate student. My lab is located in Vancouver Coastal Health Research Institute, which has a licensed animal care facility. The results will be vital for planning of maresin 1 clinical trials in the future. Despite using mice for our research, we will collaborate with vitiligo patient partners who will help ensure our findings will eventually be useful to vitiligo patients.
As people age, they can end up taking many medications. Certain medications might have made sense when they were started. But as people get older, some medications may no longer be needed, or may be unsafe. It makes sense to consider stopping such medications. It can be tough for prescribers and patients to decide when and how to stop a medication. From 2014 to 2017, we developed guidelines and resources to help patients and prescribers make decisions about stopping medications. Our guidelines and resources are used in Canada and across the world. However, guidelines and resources need to be up to date with the most current evidence. There also needs to be ongoing strategies to ensure guidelines are used in the real world. This project, led from UBC Vancouver, will first survey patients and prescribers to assess needs and priorities for guidelines on stopping medications. We will then update our guidelines based on needs and current evidence. Finally, we will design knowledge translation materials together with patients and prescribers (called “co-design”), and spread the word about our updated resources. We strive to help patients/prescribers decide when and how to stop medications and improve well-being of older adults.
Glioma is a type of brain cancer affecting patients of all ages. Modern care of the glioma patient consists of surgery, radiation treatment, and chemotherapy. Understanding the molecular makeup of the glioma can better identify how a tumour may progress than traditional pathology, which relies on what the tumour looks like under the microscope. Moreover, molecular information is crucial for treatment planning in the era of “precision oncology”, which aims to maximize tumour treatment while minimizing side effects. Without a doubt, the timely delivery of an integrated molecular glioma diagnosis is essential for quality care. We aim to achieve this via. an interdisciplinary approach, engaging researchers, pathologists, cancer physicians, and most importantly brain cancer patients at BC Cancer and Vancouver General Hospital, to integrate novel genomic technology and a re-imagined workflow to speed up brain cancer care and to reduce inequalities in access to care across BC.
Alzheimer’s disease is a major crisis and a huge burden on healthcare system. It causes a decrease in memory and affects women more than men. The memory decline in Alzheimer’s is linked to poor blood supply to the brain. The causes for poor supply are unknown but it starves brain cells of essential materials leading to improper function. I will study how a molecule present in the cells of the brain called metabotropic glutamate receptor 5 (mGluR5) contributes to the poor blood supply to the brain and the development of Alzheimer’s symptoms. My group at UBC is interested in mGluR5 because it attaches to the “toxic molecules” commonly found in Alzheimer’s brain. I will use mice sick with Alzheimer’s and samples from Alzheimer’s patients to study how the attachment of the “toxic molecules” to mGluR5 can lead to the short supply of blood to the brain and memory loss. I will also study if the role of mGluR5 in Alzheimer’s is different between males and females. In addition, I will test if the drugs that act on mGluR5 can help Alzheimer’s patients by correcting blood supply to the brain and improving memory. I also will work with patient and community partners to help interpret and communicate my findings and guide future work.
Bipolar Disorder (BD) is a psychiatric condition that affects about 2 percent of people in BC. Individuals with BD experience extreme changes in their mood, as well as their energy and ability to function. These changes, however, are frequently underreported and unrecognized — especially in youth — which can delay the diagnosis and treatment of BD by several years. Dr. Kamyar Keramatian is a psychiatrist at Vancouver Coastal Health and UBC. His research team, including people living with BD, have developed a virtual group-based educational program for youth at high risk for BD. This program aims to increase knowledge of BD, reduce self-stigma, improve help-seeking and enhance resilience in adolescents and young adults who are at high risk of developing BD. His research will explore the feasibility of implementing this new program throughout BC and how it can help young people with BD to be identified earlier and receive more timely care. By facilitating early identification and treatment of BD, his research can potentially reduce health-care costs and lead to more efficient access to care and service delivery for youth with BD across BC.
Spinal cord injury (SCI) leads to devastating muscle paralysis. My research has shown that paralysis is due, not only to interruption of communication across the damaged spinal cord, but also because of damage to the nerves and muscles outside the spinal cord, which are equally as important in producing strength. This unrecognized damage may influence prognosis and how a patient responds to treatment. Unfortunately, we do not routinely test the health of these nerves and muscles. This makes it very challenging for doctors to provide patients with accurate information about prognosis and also for patients to make proper decisions about treatment options. My project will showcase the health of nerves and muscles after SCI, using a combination of routine clinical and special laboratory techniques. This information will lead to:
- Identification of those at risk of nerve and muscle damage.
- Routine assessment of nerve/muscle health in clinical practice.
- The development of a tool to help patients make informed decisions about treatment.
The project will be conducted by my team at GF Strong Hospital and with collaborators in three other Canadian centres.
Treating advanced disease and early detection are two main challenges in lung cancer. More than half (~55 percent) of people with advanced disease are unlikely to respond to a simple standard treatment. We’ll use advanced computer-assisted analysis technology to assess a special form of x-ray — computer tomography (CT) imaging to identify people less likely to respond to usual care. This, in turn, will allow care teams to provide more appropriate care decisions. Lung cancer screening uses CT to monitor abnormalities in the lungs. Some people with “normal looking” lungs on CT may rapidly develop aggressive cancer before the next CT appointment. We will use advanced technology to assess the “normal looking” lung CT images to identify early cancer-related changes in the lung tissue that can not be seen by the human eye. This research will guide personalized care decisions and improve the survival of people with lung cancer in BC. Our multidisciplinary research team at BC Cancer Vancouver includes cancer care clinicians, scientists, and patients and families with lived or living experiences with lung cancer. We will ensure the needs and priorities of those most likely to be impacted by our research will be integrated throughout the research.
Lung cancer is the leading cause of cancer death worldwide. The number and proportion of lung cancers in people who have never smoked is projected to outpace active smokers in the next 25 years. Evidence indicates that outdoor air pollution, specifically one of its major components, particulate matter (PM 2.5), consisting of small particles measuring less than 2.5 microns in the air, is a major cause of lung cancer in never smokers. Chronic exposure to PM 2.5 can affect the layer of bacteria lining the lung (lung microbiome), changes in the lung microbiome referred to as dysbiosis have been shown to occur 10 years prior to a lung cancer diagnosis, signaling an increased risk for cancer. A promising, non-invasive tool to detect dysbiosis in the lung microbiome is studying the components of exhaled breath.
- Define the lung microbiome composition and function in people who never smoked, with and without lung cancer, including the effect of high levels of air pollution by direct bronchoscopic sampling.
- Use exhaled breath to detect early lung cancer in people who have never smoked based on the differences in the lung microbiome between cancer and non-cancer individuals.
Around 375,000 Canadians live with heart failure with reduced ejection fraction (HFrEF). HFrEF worsens quality of life, and leads to hospitalizations and death. There is no cure for HFrEF, but it can be managed with medications. Many people with HFrEF are unaware of the medications available to treat HFrEF and do not receive the best medications for them. Decision aids are tools that can help inform patients about available treatment options so they can be better involved in shared decisions about their health. This study will be conducted at UBC and will recruit from five Canadian HF clinics. This study will help us better understand what matters most to people with HF when making decisions about their medications, and use this to develop an effective decision aid to support shared decision-making. To do this, we will conduct interviews of people with HF and their healthcare professionals. After this, we will ask people with HF to complete a special online survey called a discrete-choice experiment to understand what matters most to them, and by how much, when making decisions about their HF medications. Then, we will develop a web-based decision aid and test how it improves the quality of medication-related decisions and quality of life.