Testicular germ cell tumors (GCTs) are the most frequent solid tumors in young men. Chemotherapy can cure most patients even when the tumor is advanced. However, there are still two main issues of concern.
- Survivors have an increased risk of developing other diseases (e.g. heart disease, new tumors, strokes, etc.) as results of the late side effects of chemo- and radiation- therapies.
- Current methods to detect GCTs rely on a CT scan and blood work for tumor markers which are not specific enough for GCTs. This means there are patients who are falsely considered as having the tumor and more importantly, being treated unnecessarily with chemotherapy, radiation or surgery.
Our research program aims to reduce this uncertainty by analyzing some small RNA fragments (micro-RNAs) in the blood of GCTs patients that are produced only by the GCTs cells. Although several small studies have demonstrated those micro-RNAs are better than the CT scan and serum tumor markers to detect GCTs, we still need to validate this test in a larger number of patients before it can routinely be used in clinical practice. We have therefore designed two clinical trials to validate the clinical utility of micro-RNAs in the management of GCTs.
Two out of every five individuals will develop cancer during their lifetime. My research program focuses on cancer prevention and diagnosis, using skin cancer as an initial platform. Skin cancer accounts for two thirds of all cancer cases and is an easily accessible organ to study using optical devices. Biopsies are typically used to detect skin cancers. Disadvantages of skin biopsies include possible disfigurement and complications, lengthy processing time, and occasionally inaccurate or inconclusive results. As well in some patients that are at high risk, taking multiple biopsies may not be practical and is costly. In this proposal, we will determine if an optical device combining different optical methods can readily and accurately detect skin cancer.
Ultimately, we expect this optic device to provide a noninvasive and instantaneous diagnosis that would be available to the patient and clinician at the bedside. This novel method of combining different spectroscopy methods to be able to collectively evaluate skin lesions and help in the diagnosis of skin cancer would be a significant achievement in the screening of cancer. Early and improved detection using a noninvasive method would help to improve morbidity and mortality in those affected with cancer.
Aggressive B-cell lymphomas are the most common form of lymphoma and ~50% of patients are cured with modern treatments. However, the outcomes for patients whose disease is not cured are dismal with ~10% of those patients alive at 5 years. This shows that these lymphomas, although grouped together on the basis of what they look like down the microscope, represent clusters of different lymphoma groups. A better understanding of the 'molecular wiring'of these lymphomas is critical to identify patients at high risk of resistant lymphoma and providing better treatments.
This project will provide a rational new way to group lymphomas based on differences in the molecular wiring. This will be acheived by performing and analysing genomic sequencing on a large number of aggressive B-cell lymphomas brought together through an international lymphoma consortium. Further, tumour samples will be analysed from the time of diagnosis and when the lymphoma relapses to see whether this molecular wiring remains stable or changes with treatment. It is anticipated that this major step forward in our knowledge will be translated into new tools for matching a patient's lymphoma to the correct treatment and improving patient outcomes.
Spontaneous coronary artery dissection (SCAD) occurs when there is a tear in the inner layers of a blood vessel in the heart, causing blockage and reducing blood flow and oxygen to the heart. It is an emergency condition that can result in heart attack and even death. Unfortunately, the causes of SCAD are poorly understood, and it is often misdiagnosed and mistreated.
This disease is very concerning because SCAD affect mostly young, otherwise healthy individuals, particularly women. The objective of our study is to enroll and follow 3,000 women and men who have suffered a heart attack as a result of SCAD. These patients will be recruited from across Canada, the United States, and internationally. This will be the largest and most comprehensive study on SCAD in the world.
We will follow them for up to 10 years and evaluate how their initial treatment (surgery, stenting, or medication) affects their in-hospital recovery and long-term health outcomes. We will also assess for underlying causes of SCAD that include pregnancy or abnormal growths causing narrowing of the walls of the arteries. We will also perform genetic tests in a large subset of these patients to determine if there are genes we can use to screen off-springs of patients. We will also examine how these conditions can affect the future risks of cardiovascular events, such as another heart attack, stroke, or death. This innovative research study will help generate guidelines to diagnose, investigate and treat SCAD.
Interstitial lung disease (ILD) is a progressive lung disorder with no effective treatment. Oxygen is often used to relieve symptoms at the end of life, but the evidence supporting oxygen use in these patients is based on limited data from other diseases. The lack of data on the benefits of oxygen in patients with ILD has resulted in uncertain criteria for its use and limited access to this potentially important medication.
My proposed research includes a detailed evaluation of the clinical, biological, and prognostic impact of oxygen in patients with ILD. My main objectives are to determine (1) the rate of progression and prognostic significance of low oxygen levels in patients with ILD, (2) the clinical and biological benefits of night-time oxygen in patients with ILD, and (3) the impact of oxygen on the use of medical services in patients with ILD and other forms of chronic lung disease.
This research will provide a thorough understanding of the role of oxygen in patients with ILD. These findings will inform patients, physicians, and policy makers on the appropriate use of oxygen in this setting, with additional components of this research that are aimed at identifying potential mechanisms of ILD worsening.
Acute kidney injury (AKI) complicating critical illness is an important problem, contributing to roughly 1.7 million deaths worldwide per year. Treatment is limited to dialysis, which is costly and frequently unavailable. Preventing AKI is a critical step to reduce deaths. Acetaminophen (Tylenol) has the potential to reduce AKI caused by oxidative damage from hemoglobin (released from red blood cells) and myoglobin (released from muscle cells). Acetaminophen inhibits this oxidative damage and reduces kidney dysfunction in animal models, and in patients after cardiac surgery or in patients with sepsis.
I previously led a trial in adults with severe malaria showing that acetaminophen improved kidney function and reduced the odds of developing AKI. Since children bear the major burden of malaria, it is crucial to test this protective effect in African children where 45% of patients have AKI. The goal is to assess the role of acetaminophen as a kidney protective therapy in severe malaria.
I will conduct a randomized controlled trial of adjunctive acetaminophen in African children with severe malaria. If the trial is positive, the results would change severe malaria management globally. It could be rapidly scalable as acetaminophen is inexpensive, safe and widely used. These findings will have broad implications for other major causes of hemoprotein-mediated AKI including crush injury and sepsis, which directly impact thousands of Canadians.
Introduction: Colorectal cancer (CRC) is the second most common cancer. Once metastatic, patients are generally incurable and receive treatment to prolong survival. Immunotherapies use a patient's immune system to attack their cancer. These treatments are effective in CRC patients with microsatellite instability (MSI). Unfortunately, 95% of patients lack MSI and are called microsatellite stable (MSS). This group usually doesn't respond to immunotherapy and we need to explore why.
Specific Aims:
We aim to identify:
- why some MSS patients benefit from immunotherapy, and
- what can we target to activate immune cells in patients who don't respond to immunotherapy.
Methods: We will investigate how the immune system and tumors interact in patients from two clinical trials. These trials evaluated immunotherapy in MSS CRC. Blood and tumor samples from these trials will be tested to identify features that predict response. These results will then guide the creation of new clinical trials with immunotherapy for CRC using our findings.
Significance: Immunotherapy does not work for the 95% of CRC patients who are MSS. We will identify how to activate the immune system in CRC patients with MSS so they too can benefit from immunotherapy.
Women who inherit a BRCA gene mutation are at high risk for breast cancer and the most lethal type of ovarian cancer, high-grade serous ovarian carcinoma (HGSC).
A woman diagnosed with HGSC has a 20% chance of unknowingly carrying a BRCA mutation, and is eligible for genetic testing. Getting a blood sample to do genetic testing in this woman is critical, because if she is found to have a BRCA mutation: 1) her relatives (daughters, sisters) can be tested, and HGSC can be PREVENTED in them, and 2) she herself can be treated with PARP inhibitors that can improve survival.
The problem, however, is that the yield of genetic testing is low, and only 30% of women with HGSC undergo such genetic testing. This excludes 70% from effective treatment and leaves their family members at high risk. How can BRCA mutations be better identified?
One strategy is to begin with testing the HGSC tumour itself. If the tumour has a BRCA mutation, PARP inhibitor treatment can be given. These women can then be targeted for genetic testing, and 2/3 of them will have an inherited BRCA mutation. This improves the efficiency of genetic testing, rather than referring everyone with HGSC.
Tumour testing of HGSC is not routinely done in BC. Hence, I propose to conduct a pilot study of tumour testing for BRCA mutations in HGSC, and a cost-effectiveness analysis of its impact on ovarian cancer survival and future cancer prevention, to justify this testing in this patient population.
The World Health Organization (WHO) aims to eliminate TB by 2050, but Canada is not on target to meet that goal. To reach our national TB elimination targets, we must reduce TB rates by 10% per year but we are only reducing TB rates by 2% per year. My research program is aimed at developing evidence to improve TB screening, prevention and treatment policies in order to accelerate TB elimination in British Columbia (BC) and Canada.
In my primary research project, my team is using provincial health databases to describe TB epidemiology in the foreign-born population of Canada. Our goal is to develop a TB risk score and to create evidence that informs cost-effective TB screening policy. My team is also using TB genome sequencing data to understand TB transmission networks and to find areas for public health intervention. Lastly, we are developing evidence to improve treatment outcomes for people affected by TB.
Deaths due to opioid overdoses have reached epidemic proportions in Canada, with nearly 8,000 Canadians losing their lives in the last two years. Knowledge of how rescuers can best respond to cardiac arrests due to opioid overdose is urgently needed.
Unfortunately, there is a paucity of studies examining opioid-related cardiac arrest; therefore, there is a lack of evidence to guide bystanders or professional rescuers on how best to intervene. Specifically, there is controversy regarding the benefit of bystander-initiated rescue breaths and paramedic-delivered naloxone. The goal of this project is to determine best resuscitative strategies for opioid-related cardiac arrest to inform national and international guidelines.
In this project I will create the largest and most comprehensive dataset of cardiac arrest cases due to opioid overdose in the world, complete with detailed data on bystander and professional interventions, and patient-oriented outcomes. I will analyze this data to determine the best treatment strategies. In addition, I will examine the benefit of public access opioid overdose kits and their optimal locations. I will implement a knowledge translation and dissemination plan in collaboration with key knowledge-users.
