PhD defence X. (Xinhui) Wu

Regenerative pharmacology for COPD

Xinhui Wu investigated novel therapeutic targets for chronic obstructive pulmonary disease (COPD). COPD is one of the most common lung diseases worldwide. It is characterized by airflow obstruction in the lung that causes breathing difficulties, cough, mucus (sputum) production and wheezing. The main causes of COPD are tobacco smoke and air pollution. They key problem in COPD is defective tissue repair, causing chronic bronchitis and emphysema, which are the two most common conditions resulting from airway and/or alveolar abnormalities. However, the current treatments for COPD can only reduce the symptoms and do not reverse or slow down the progression of the disease. Ms. Wu focused her research on the mechanisms underlying cigarette smoke and air pollution-induced dysfunctional lung repair and discovered several potential regenerative drug targets beneficial to lung repair in COPD.

By using novel tools, such as 3D organoids and the precision-cut-lung slices (PCLS), to model different pathological conditions, Ms. Wu identified that cigarette smoke and air pollution both cause defective lung repair, but with different mechanisms. Molecular pathways such WNT-5A/B signaling, TGF- signaling, growth factors related signaling, cell death related signaling and circadian clock signaling all appear to play fundamental roles in the defective functions of alveolar epithelial progenitors. Several pharmacological strategies, such as ROCK inhibitors; antioxidants such as NAC and MitoQ; the analogues of PGE2 and PGI2 were discovered as potential regenerative therapeutic targets in lung repair for COPD.

Promotores: Prof.dr. R. Gosens and Prof.dr. M. Schmidt