Toward an immunohistochemical model for molecular subtyping and predicting of treatment response in bladder cancer

Bladder cancer has an increasing incidence in North America and represents a significant healthcare burden. At the molecular level, it is a diverse disease with heterogeneous clinical outcomes and treatment responses. Immunohistochemistry (IHC) has been applied to predict molecular subtypes with good reliability. In our previous study, we calculated the accuracy of uroplakin II (UPII), a marker of urothelial differentiation, to predict molecular-based luminal versus basal subtypes of bladder cancer. Our previous proteomics studies have also identified a list of potential proteins associated with the patients’ prognosis and chemotherapy response. The overall objective of the current study is to identify an IHC marker panel to accurately predict the molecular subtypes of bladder cancer and their response to chemotherapy. This proposed study will demonstrate that IHC markers could reliably identify the luminal and basal molecular subtypes. The semi-quantitative visual assessment of these markers in routine pathological preparations will be a valuable tool in identifying bladder cancer’s molecular subtypes and improving the selection of MIBC patients most likely to benefit from neoadjuvant chemotherapy.

Precision Nutrition for Digestive Diseases: Bridging the Gap through Translational Nutrition Research (PRECISE Study)

Inflammatory bowel disease (IBD) affects the digestive tract causing stomach pain, diarrhea, fatigue, and weight loss. Patients notice that diet impacts their symptoms and how they feel. While studies have explored the link between diet and IBD and how it develops, a gap exists in understanding how diet can treat inflammation and symptoms. Recent research indicates a crucial role for diet in shaping the microbiome (tiny microbes in our gut), potentially reducing the risk of disease flares. Understanding how diet affects the microbiome in IBD is key to empowering patients to take control of their condition.

Not all patients respond to diet in the same way. My research program will use precision nutrition (PN) to study the different responses to diet therapy based on an individual’s microbiome. In the future, we will aim to provide diet recommendations tailored to the person, leading to better disease management, improved nutritional health, and reduced symptoms.

This research project can impact patients’ daily diet practices and provide crucial guidance for health professionals and patients, which is currently lacking. Also, its potential impacts extend to shaping future policies and research directions in diet for IBD.

Using an equity-informed approach to enhance care for children and youth with a neurological condition in British Columbia

Neurological conditions are a major concern for children and youth, with the potential to affect both physical and mental health. These conditions occur as a result of injury, genetics, and exposures which disrupt the normal functions regulated by the nervous system. Despite the reported rates of neurological conditions in Canada, there are no current estimates of children and youth in British Columbia (BC) living with these conditions. Further, there is a lack of understanding on how this population accesses health care. Therefore, we want to quantify the rate of neurological conditions by exploring the current prevalence of in the BC pediatric population. Second, we will identify the barriers to accessing neurological care, focusing on the social determinants of health. Lastly, we seek to address inequities by investigating the implementation of nursing-led care (i.e., assessment, education, and intervention) for children waiting to access neurological care. This work is equity-oriented, with a focus on underserved groups. Research will be performed at UBC and BC Children’s Hospital with input from key stakeholders across BC to enact knowledge translation, seeking to inform practice and create system level interventions.

Longitudinal non-invasive optical biopsy of skin cancers to monitor efficacy and response to treatment

1 in 5 British Columbians will develop skin cancer. To detect cancer cells, a skin sample is typically removed surgically and studied through a microscope (known as histology). Unfortunately, this is invasive and has risks such as pain, infection, bleeding and scarring, which makes it impractical to perform repeatedly.

My research program focuses on using non-invasive optical imaging methods as an alternative to surgical biopsy, to provide microscopic views of the skin and to detect the presence of cancer cells. We will study 300 patients being treated for skin cancer and scan them to check for cancer cells at regular intervals. Through this, we will 1) evaluate how effective non-surgical treatments are for clearing cancer 2) study the behaviour of cancer cells after therapy and 3) compare optical findings to histology to confirm our results.

My research will offer a novel way of monitoring skin cancer, without undesired effects to the patient. This will improve cancer care by increasing our understanding of skin cancers, efficacy of treatments, and by guiding treatment to improve cure rates. This will provide crucial insights on how best to use less-invasive treatments and help improve patient experiences with cancer therapy.

Investigating novel, non-chemotherapy, targeted treatment strategies in high grade serous ovarian cancer

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:

  1. Do chemotherapy-free targeted treatments work in OC and which drug combinations are best?
  2. Which order treatments should be given, before or after chemotherapy?
  3. 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.

Maresin 1 as a novel therapy for vitiligo

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.

Making medications fit for older adults: advancing the science and implementation of deprescribing guidelines

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.

Accelerating comprehensive diagnosis of glioma patients in BC: the long and short of it

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.

Clinical applications and implementation of artificial intelligence in lung cancer: predicting treatment response in advanced disease and risk of malignancy in lung cancer screening

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.

Evaluation of a manualized telehealth-based psychoeducation group for individuals at high risk for bipolar disorder

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.