Olschewski A ⏩
• Olschewski H
The RESPImmun Faculty
Andrea Olschewski is an anesthesiologist and electrophysiologist with interest in the regulation of the pulmonary circulation. With her expertise in biophysics, molecular physiology of ion channels she has done pioneering work characterizing the role of ion channels in the human pulmonary vasculature. She has also explored the role of chemokines in vascular smooth muscle function in PH. Within RESPImmun she closely collaborates with Ákos Heinemman (inflammation), Leigh Marsh (animal models), Grażyna Kwapiszewska (molecular biology), Gerald Höfler (lung pathology), Horst Olschewski (clinical samples).
ProjectProject 9: The chloride channel regulator CLCA1 and the calcium-activated chlorid channel TMEM16A in lung fibrosis
Co-PI: Chandran Nagaraj
BackgroundIdiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease. The majority of patients have median survival of
Hypothesis and objectivesWe hypothesize that the CLCA1 / TMEM16A axis is a novel player in idiopathic pulmonary fibrosis. We will futher characterize the CLCA1 / TMEM16A expression and function in healthy and IPF human lungs and their manipulation by inflammatory modulators leading to parenchymal remodeling and thus to pulmonary fibrosis. Proof-of-concept studies will be performed in mouse models of pulmonary fibrosis.
MethodologyIn this project the student will: (i) investigate CLCA1 level in the bronchoalveolar lavage fluid (BALF) and lung homogenate samples from the explanted IPF lungs; (ii) investigate the role of TMEM16A on epithelial cells and its upstream and downstream signaling in lung fibrosis with special focus on inflammatory markers; (iii) prove the importance of TMEM16A in in vivo models of lung fibrosis. Year 1: The PhD student will learn to isolate primary epithelial cells from explanted human lungs. CLCA1 / TMEM16A expression and localisation will be examined by qPCR and flow cytometry followed by confocal fluorescence microscopy. Circulating plasma CLCA1 levels will be measured by ELISA in human samples and in the animal models of pulmonary fibrosis. Year 2: Functional role of CLCA1 / TMEM16A manipulation of epithelial cells will be investigated by patch-clamping, live cell calcium imaging and its impact on cell proliferation and secreted inflammatory mediators. Year 3 – 4: The student will analyse the CLCA1 / TMEM16A axis in well-established experimental mouse models for pulmonary fibrosis (bleomycin-induced fibrosis model and Fra2 overexpressing mice).
Input from collaborations within the RESPImmun programme