Elucidating the roles and therapeutic targeting of molecular drivers of chronic obstructive pulmonary disease (COPD)/emphysema
- Publication Type:
- Thesis
- Issue Date:
- 2023
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Chronic obstructive pulmonary disease (COPD) is a complex, irreversible respiratory condition characterized by inflammation, excessive mucus production, and tissue damage in the lungs. Cigarette smoke (CS) is one of the fundamental risk factors driving COPD pathogenesis. Currently, there are no treatments that stop the progression or reverse the condition, and the focus is solely on symptom management. This thesis aimed to identify molecular targets to mitigate CS-induced lung damage in COPD. Firstly, longitudinal gene expression profiling in a CS-induced experimental COPD, highlighted that the dynamic interplay of smoke protective genes between COPD onset and progression becomes exhausted with constant CS exposure. We then integrated the gene and miRNA expression patterns to understand disease pathogenesis and regulation at the post-transcriptional level in response to CS that induced COPD. Lastly, we screened the whole genome against CS using a CRISPR-based genome-wide loss-of-function approach to investigate the targets whose inhibition could hamper CS-induced damage. Overall, this thesis offers insight into the molecular mechanisms underlying CS-induced COPD at the transcriptional and post-transcriptional level, along with the genome-wide functional screening, to define potential candidates that can be targeted in the future to hinder the progression of CS-induced lung damage especially in COPD.
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