Understanding targetable pathways that drive Chronic Mucus Hypersecretion in patients with Chronic Obstructive Pulmonary Disease

Thus far, the phenotyping and endotyping of COPD is lagging behind. The aim of the current research proposal is to establish a cohort of patients with mild, moderate and severe COPD as well as healthy controls. We will use an innovative systems biology approach to identify i) those COPD patients with Chronic Mucus Hypersecretion, ii) potential treatable traits, and iii) novel therapeutic targets in COPD. The overall aim of this project is identification of candidate genes and pathways that are differently expressed and alterations in the lung microbiome with disease severity and associated with the progression of the disease. This is expected to lead to identification of novel therapeutic targets for COPD and chronic mucus hypersecretion in particular as well as biomarkers for those patients at risk to progress to severe disease. 

The aim of this project was to discover novel mechanisms and possible treatment targets underlying the different subtypes of COPD, including the chronic mucus hypersecretion (CMH) and severe, and severe early-onset COPD subtypes. To address the overall aim of the project, several collaborative studies were performed by scientists from UMCG, Genentech and UTS, with main roles for the two PPP-funded PhD students. Several types of analysis were performed, for example, on the transcriptomics dataset focused on the role of alternative splicing in severe COPD. These findings were published in numerous research Journals.

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