P07 - Disease - and cell type-specific responses of human bronchial epithelial cells to cigarette smoke

Given their critical role in first-line defense against environmental agents, bronchial epithelial cells play an important role in the etiology of many chronic lung diseases. Cigarette smoke remains the major risk factor for some of the deadliest global diseases, including e.g. chronic obstructive pulmonary disease (COPD) and lung cancer, but also for idiopathic pulmonary fibrosis (IPF), a comparatively rare but particularly progressive and fatal interstitial lung disease. This project aims to elucidate relative cellular contributions and disease-specific pathogenic mechanisms in the response to cigarette smoke. We will use existing proteomic and scRNA-Seq data sets from patient samples and in vitro smoke exposure experiments to extract disease-specific smoke signatures and differentially activated pathways and address them functionally in a validated in vitro cigarette smoke exposure model.

Project-related publications:

1. Schamberger AC, Staab-Weijnitz CA, Mise-Racek N, Eickelberg O. Cigarette smoke alters primary human bronchial epithelial cell differentiation at the air-liquid interface. Sci Rep 2015; 5: 8163
2. Schamberger AC, Schiller HB, Fernandez IE, Sterclova M, Heinzelmann K, Hennen E, Hatz R, Behr J, Vasakova M, Mann M, Eickelberg O, Staab-Weijnitz CA. Glutathione peroxidase 3 localizes to the epithelial lining fluid and the extracellular matrix in interstitial lung disease. Sci Rep 2016; 6: 299521.
3. Andrault PM, Schamberger AC, Chazeirat T, Sizaret D, Renault J, Staab-Weijnitz CA, Hennen E, Petit-Courty A, Wartenberg M, Saidi A, Baranek T, Guyetant S, Courty Y, Eickelberg O, Lalmanach G, Lecaille F (2019). Cigarette smoke induces overexpression of active human cathepsin S in lungs from current smokers with or without COPD. Am J Physiol Lung Cell Mol Physiol, 317(5):L625-L638.
4. Mossina A, Lukas C, Merl-Pham J, Uhl FE, Mutze K, Schamberger A, Staab-Weijnitz C, Jia J, Yildirim AÖ, Königshoff M, Hauck SM, Eickelberg O, Meiners S. (2017). Cigarette smoke alters the secretome of lung epithelial cells. Proteomics, 17(1-2)
5. Knüppel L, Ishikawa Y, Aichler M, Heinzelmann K, Hatz R, Behr J, Walch A, Bächinger HP, Eickelberg O, Staab-Weijnitz CA (2017). A Novel Antifibrotic Mechanism of Nintedanib and Pirfenidone. Inhibition of Collagen Fibril Assembly. Am J Respir Cell Mol Biol, 57(1):77-90 (IF 2017: 3.79)
6. Staab-Weijnitz CA, Fernandez IE, Knüppel L, Maul J, Heinzelmann K, Juan-Guardela BM, Hennen E, Preissler G, Winter H, Neurohr C, Hatz R, Lindner M, Behr J, Kaminski N, Eickelberg O (2015). FK506-Binding Protein 10, a Potential Novel Drug Target for Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med, 192(4):455-67
7. Schiller HB, Mayr CH, Leuschner G, Strunz M, Staab-Weijnitz C, Preisendörfer S, Eckes B, Moinzadeh P, Krieg T, Schwartz DA, Hatz RA, Behr J, Mann M, Eickelberg O (2017). Deep Proteome Profiling Reveals Common Prevalence of MZB1-Positive Plasma B Cells in Human Lung and Skin Fibrosis. Am J Respir Crit Care Med, 196(10):1298