Don Sin is the Director of the Centre for Heart Lung Innovation (HLI), a Professor of Medicine at University of British Columbia (UBC) and respirologist at St. Paul’s Hospital (SPH). He holds a Tier 1 Canada Research Chair in COPD and the De Lazzari Family Chair at HLI. He has published 700 peer-reviewed papers and has an H-index of 110. He obtained his medical degree at University of Alberta in 1991. He currently serves on the Global initiative for chronic Obstructive Lung Disease (GOLD) scientific committee and CTS COPD guidelines committee and is the deputy chief editor for the European Respiratory Journal. His research focus is using “omics” data to discover novel biomarkers of disease activity and new therapeutic targets to reduce hospitalization and mortality in patients with COPD.
Because COPD is a heterogeneous disorder, large sample sizes are generally required for therapeutic and even mechanistic studies to enable sufficient statistical power. This problem is exacerbated by the fact that even within a given COPD lung, there is tremendous variability in the severity and extent of the disease.
With the advent of in vivo imaging techniques such as high-resolution CT scans and more recently functional magnetic resonance imaging (MRI), structural abnormalities and disease activity levels can be detected and mapped out regionally prior to sampling of small airways, which are the primary site of disease in COPD (e.g. sampling can be done using bronchoscopy). By knowing which regions of the lung are “hot” and which are “quiescent” a priori, bronchoscopists can take samples in a targeted way to ensure that the full spectrum of disease activity is represented in the sampling process and more importantly, that there is alignment of histologic, molecular and microbial changes in these samples with the disease activity readouts from in vivo imaging.
Over the next 7 years, we will optimize the use of hyperpolarized 129Xe MRI imaging for COPD. In the same subjects, we will also perform research bronchoscopies and sample different small airways based on disease activity readouts from the in vivo imaging. We will then perform multi-omics evaluation of bronchoscopic brushes (which are >95% pure epithelial cells) and bronchoalveolar lavage fluid (BALF). The multi-omic evaluation will include:
- 16S sequencing for the microbiome;
- Bulk RNA-seq (and single cell seq for sub-projects);
- DNA methylation and other epigenetic interrogations; and others.
The cellular components of BALF are >80% macrophages, which can be profiled, and the supernatant can be used to evaluate surfactants, cytokines/growth factors and other molecules that may play an important role in COPD pathogenesis.