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Kengo Koike, M.D., Ph.D.

National Jewish Health
Understanding Enzyme Involved in Development of COPD

Chronic obstructive pulmonary disease (COPD) is usually caused by cigarette smoking. There is no cure, and the mechanisms behind the development and progression of the disease remain incompletely understood. We will study the process that produces fat-like substances called bioactive lipids in lung cells. The levels of these lipids, called sphingolipids are significantly changed in plasma of COPD patients who are prone to have inflammation episodes in their lung. By understanding a key enzyme that controls how much sphingolipid is synthesized, we can develop tools to reduce the chance for lung cells to be destroyed by smoke and ultimately decrease lung injury and inflammation caused by smoking.

Update: Our data suggest that the enzyme we are studying, glucosylceramide synthase (GCS), plays an important role in survival of cells in human lungs, called pulmonary endothelial cells, by regulating signaling pathways that cells utilize to sense nutrients. If cells sense a lack of nutrients, they trigger a process called autophagy in order to survive. During autophagy, cells disassemble unnecessary or dysfunctional components in order to maintain cell survival. Emerging evidence indicates that autophagy plays an important role in the development of COPD. We anticipate that our findings will enhance the understanding of mechanisms of cigarette smoke-induced lung blood vessel dysfunction, which can be used to design therapy.

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