Grant: Foundation Grant

<html> <body> <p>Chronic obstructive pulmonary disease (COPD) is the <strong>number one</strong> cause of hospitalization in Canada, responsible for 80,000 admissions per year. Worldwide it is the 3^rd leading cause of death, responsible for 3 million deaths per year. Regrettably, there are no therapies that can modify disease progression or reduce mortality.&nbsp;One major barrier in the care of patients with COPD and for drug discovery has been the lack of simple biomarkers to indicate which patients have active disease and which ones have "burnt out" disease. <em><strong>Our vision is to enable and accelerate drug discovery, improve disease management and ultimately reduce morbidity and mortality of COPD patients by identifying biomarkers of disease activity in COPD using multi-omics technology.</strong></em> The <strong>primary aims</strong> of this 7-year program are to:</p> <p>Aim 1: discover biomarker signatures in small airways that are predictive of COPD disease progression, defined as FEV₁ decline over time.<br> <br> Aim 2: discover biomarker signatures in peripheral blood that are predictive of COPD disease progression and mortality over time.<br> <br> The <strong>secondary aims</strong> of the program are to integrate -omics data from small airways and peripheral blood with phenotypic and clinical data and:<br> <br> Aim 3: determine novel therapeutic targets to mitigate disease activity and improve health outcomes of COPD patients.<br> <br> Aim 4: identify differentially regulated pathways between male and female patients and determine molecular drivers of sexual dimorphisms in COPD.<br> <br> Aim 5: determine the relationship of small airway microbiota with severity and progression of COPD.<br> <br> Our program is enabled by: 1) a large number of biological tissues (e.g. lung tissue specimens, bronchial epithelial cells from small airways and blood) of current and former smokers from multiple well-phenotyped COPD cohorts; 2) expertise with and access to well established -omics technology platforms including multiple reaction monitoring-mass spectrometry (MRM-MS), DNA methylation, gene expression profiling and 16S meta-genomic sequencing that will be used to interrogate the role of airway inflammation, oxidative stress and lung microbiota on disease pathogenesis and progression; 3) a multi-disciplinary team of seasoned investigators, who bring complementary skills and most importantly have worked together for years to solve clinical problems in COPD. We have COPD clinicians (Sin, Tan, S. Lam, Par&eacute;), imagers (Coxson), computational biologists (Ng, Hollander), geneticists (Sandford), platform experts in methylation (Kobor), transcriptomics (Nislow), proteomics (Borchers), genetics (Sandford, W. Lam), microbiome (Hogg), trainees (Obeidat, Leung) and end-users (McManus, DeMarco); 4) a leading bioinformatics and computational program geared towards biomarker discovery and implementation; and 5) a strong translational research training program, focused predominantly on post-doctoral fellows (PDFs) and clinician-scientists, empowering them with -omics technology, data integration and clinical application.<br> <br> At the end of the 7 years, we anticipate generating a biomarker panel of disease progression that is ready for clinical implementation, a series of novel therapeutic targets (that will be tested in collaborations with our industry partners), and training of at least 10 PDFs (7 clinician-scientists) and several graduate students, who will have expertise in biomarker discovery and clinical development.</p> </body> </html>