Genome-wide characterization of microRNA and gene expression patterns in smoking-related lung disease

• Main Author: Campbell, Joshua David
• Language: en_US
• Published: Boston University 2015
• Online Access: https://hdl.handle.net/2144/12307

Thesis (Ph.D.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at [e-mail]. Thank you. === Smoking-related lung diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer are significant public health concerns world-wide. High throughput genomic technologies have opened up a new realm of understanding into the complexities of human disease by providing a means by which we can gain considerable amounts of information about a sample. In my research, I examine genome-wide gene expression via microarrays and microRNA expression via small RNA-sequencing (small RNA-Seq) to gain insights into lung disease pathogenesis, assess novel strategies for identifying therapeutics, and develop biomarkers for earlier diagnosis of disease. First, I revealed mechanisms of emphysema progression within individuals by leveraging a unique dataset that contains multiple lung-tissue samples per patient collected from regions with different levels of emphysematous destruction. Pathways involved in immune response and tissue remodeling were enriched among gene expression profiles associated with increasing regional emphysema severity. Using the Connectivity Map, a compound was discovered capable of reversing the gene-expression signature of increasing emphysema severity which can serve as a lead in therapeutic development for COPD. [TRUNCATED]