University of Giessen Lung Center

Phosphodiesterases

Cyclic nucleotide phosphodiesterases (PDE) comprise a family of related proteins, which can be subdivided into 11 families based on their amino acid sequences, sensitivity to different activators and inhibitors and their ability to hydrolyze either preferentially cAMP or cGMP or both. cAMP and cGMP being ubiquitous second messengers propagates many signaling pathways including proliferation, migration, and differentiation. To attenuate PDE influenced pathological processes, specific inhibitors are successfully used in different lung diseases. Based on my preclinical work in animal models of pulmonary hypertension the PDE 5 inhibitor sildenafil was approved for treatment of pulmonary hypertension. Additional work of my research group in this field demonstrated that other PDEs (e.g. PDE1) are dysregualed as well. We know that under disease conditions the control of cyclic nucleotides via PDEs plays a crucial role in proliferation and apoptosis in different cell types. The goal in this research topic will be the investigation of the role of PDEs in lung fibrosis, lung emphysema and malignant diseases.