PhD position Molecular Pharmacology (1.0 fte)
The Groningen Research Institute of Pharmacy (GRIP) of the Faculty of Science and Engineering has a position for a PhD candidate in the department of molecular pharmacology. The project is funded by a grant from The Netherlands Lung Foundation. The project is a collaboration between the University of Groningen and the University of Colorado (Denver, USA): the candidate will spend 2 years of research time at both institutes.
Chronic obstructive pulmonary disease (COPD) is characterized by a progressive loss of lung function with airflow obstruction that is not fully reversible. The key problem underlying COPD is defective airway and alveolar repair in response to inflammation and oxidative stress, causing bronchitis, small airways remodeling and emphysema. As current therapies do not modify the course of the disease in COPD, new therapies need to be developed.
Epithelial progenitor cells of the distal lung interact with structural cells such as fibroblasts to contribute to lung repair, which is driven by canonical WNT/β-catenin signaling. This mechanism is impaired in COPD, in part because chronic inflammation and oxidative stress provide a hostile local microenvironment in the COPD lung, not only causing damage, but also hampering repair responses. Inflammation and oxidative stress directly and indirectly affect canonical WNT/β-catenin signaling (responsible for repair). The successful PhD candidate will therefore investigate in this project whether reversal of this process using targeted pharmacological inhibition is possible. We hypothesize that the distortion of regenerative signaling is driven by a canonical to non-canonical WNT signaling switch, skewing signaling towards pro-inflammatory pathways, which lead to halted repair. These pathways provide rational drug targets for alveolar repair and we propose that it is possible to restore lung repair by targeting these pathways.
A team of pharmacologists, pathologists, (stem) cell biologists and pulmonologists will form a consortium to investigate this hypothesis in detail. We seek a PhD student to lead this effort in investigating i) how inflammation and oxidative stress promote a canonical to non-canonical WNT signalling switch; ii) whether this pathway cross-talk contributes to impaired lung repair in COPD; and iii) whether these pathways can be targeted pharmacologically in order to restore endogenous and progenitor cell mediated repair.
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