Grant: CIHR Fellowship

Lung inflammatory diseases, including asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD) and bronchitis, are one of the most common and insidious causes of death on the planet. To date we know little about the mechanisms involved or the optimal anti-inflammatory treatments for each of the various lung inflammatory syndromes. In Cystic Fibrosis (CF), pulmonary hyper-inflammation is the single most significant contributor to disease progression and the effective control of inflammation-mediated lung destruction is critical to prolonging the life of those who suffer with this disease. Understanding the inflammatory component of human diseases is difficult due to the dynamic and interconnected nature of the immune system. My proposed research project is to adopt a top-down systems approach, using a combination of functional genomics and cell biology, to investigate bacterially induced pulmonary hyperinflammation in CF. The project will be carried out in two stages. In the first stage, I will use next-generation transcriptomics and metabolomic profiling technologies to generate detailed information and hypotheses about cellular networks leading to CF pulmonary inflammation. In the second stage, I will further characterize roles of the key intermediates of the networks using a combination of different inhibitory or activating reagents on CF epithelial cells. The mechanisms of a promising immunomodulatory peptide, IDR-1018, will also be studied thoroughly in this context. Upon the completion of the project, I will have substantially increased our understanding of the molecular mechanisms of hyperinflammation in CF and deciphered the detailed mechanism of how IDR-1018 modulates the inflammatory response in CF epithelial cells. The results will provide knowledge and insight that will be critical in designing new effective anti-inflammatory treatments for CF lung disease.