Drs. Ying Wang (left) and Joshua Dubland (right) are recipients of the 2022/2023 Precision Health Catalyst Grant award for their project entitled “Who will benefit from colchicine to reduce heart attacks? Characterizing the baseline inflammation status of patients with coronary atherosclerosis”
Read a summary of the project here.
“This project aims to provide molecular insights on the baseline inflammation present in the coronary lesions (local) and plasma (systemic) of patients with chronic and acute coronary syndrome. This project will fill knowledge gaps to enable personalizing the use of colchicine and all the future anti-inflammatory therapies.”
1. Can you tell us about the precision health research work you’re collaborating on?
Our team aims to answer the question: Who will benefit from the anti-inflammatory drug colchicine to reduce heart attacks?
Heart attack, mostly caused by the buildup of lesions in the coronary arteries, is the 2nd leading cause of death in Canada. Inflammation was recently confirmed to be an independent risk factor and therapeutic target for patients with established lesions. To prevent heart attack in these patients, an anti-inflammatory drug, colchicine, was approved by Health Canada in 2021. However, clinical trials have shown that some patients benefit from colchicine and some don’t. Currently, clinical symptoms are used to decide who will benefit from colchicine. There is no blood-derived biomarker to guide the use of colchicine in patients with established coronary lesions.
Our team will fill this knowledge gap in precision medicine by:
1. Characterizing inflammation in coronary lesions: are the therapeutic targets of colchicine present in the diseased vessels
2. Exploring blood biomarkers that are correlated with high inflammation in coronary lesions
2. What results have you seen so far?
Leveraging existing resources at the Bruce McManus Cardiovascular Biobank, where coronary lesions from heart transplant patients along with the clinical information have been archived in the past 30 years, we used high-throughput RNA sequencing to find inflammatory targets in diseased tissues. Among patients that seem to be similar in clinical symptoms, the inflammatory targets in diseased vessels vary a lot. This may explain why some patients respond well to colchicine and some don’t. We’ve also found some common inflammatory targets that different patients share.
Collaborating with the Prevention of Organ Failure Centre of Excellence, we collected pre-transplant blood samples from the same patients whose coronary lesions were sequenced for inflammatory targets. We have developed a mass spectrometry-based method to characterize promising blood biomarkers related to inflammation in coronary lesions. We are now positioned to correlate blood profiles with inflammatory status in diseased vessels.
3. From your perspective, what do you think is exciting about the future direction of precision health?
Our preliminary data suggested that clinical symptoms may not precisely predict who will benefit from colchicine treatment. Therefore, clinical guidelines need a better biomarker to assess the inflammation status in the diseased vessels for decision-making. These data generated with the help of the Precision Health Catalyst Grant award, has scaled up to three years of Heart and Stroke Foundation Grant-in-Aid research project. To advance precision health in patients with a high risk of heart attack, we will continue our correlation analysis and expand our patient cohort to find blood-derived biomarkers correlated with inflammation in the diseased vessels.
About Drs. Ying Wang and Joshua Dubland
Dr. Ying Wang is a Michael Smith Health Research BC Scholar and a Heart and Stroke Foundation of Canada New Investigator at Centre for Heart Lung Innovation, St. Paul’s Hospital. Her research program integrates cutting-edge ‘Omics’ technologies, biobank resources, and mechanistic studies to improve treatment outcomes of ischemic heart disease. In 2022, Dr. Wang was appointed as the Director of Bruce McManus Cardiovascular Biobank, which has the largest collection of explanted hearts in Canada.
Dr. Joshua Dubland is a Clinical Assistant Professor in the Department of Pathology and Laboratory Medicine at the University of British Columbia, an investigator at the BC Children’s Hospital Research Institute, and a scientist in the Newborn Screening and Biochemical Genetics Laboratories at BC Children’s Hospital. His current research interests and expertise are in utilizing mass spectrometry for biomarker discovery, assay development, and implementation of novel testing strategies in the clinical laboratory.