Disease Area Coordinators

Prof. Dr. Marcus A. Mall (TLRC), Prof. Dr. Dr. Burkhard Tümmler (BREATH)

(Administr. Coordinator: Dr. Birgit Teucher (TLRC))

Contributing Partner Sites

ARCN, BREATH, UGMLC, TLRC

OVERVIEW

Cystic fibrosis (CF) is the most common genetically determined, early onset and still lethal form of chronic obstructive lung disease. CF affects approximately one in 2500 newborns in Caucasian populations. With improvements in symptomatic therapies and standardized CF medical care, the median survival of CF patients in Germany has increased to approximately 40 years of age. However, despite recent breakthroughs in disease-modifying therapies for a small subgroup of patients with specific CF genotypes, there are currently no therapies available that target CF lung disease at its root cause in the majority of patients.  The overall aim of the DZL CF research program is to advance the current understanding of the pathogenesis of CF lung disease and to use this knowledge to improve CF diagnostics, develop more sensitive tools for monitoring of disease activity, and develop novel strategies for effective prevention and therapy of CF lung disease. 

MAJOR RESEARCH GOALS

  • Establish a CF infant cohort for studies of early CF lung disease and clinical evaluation of novel preventive/early therapeutic interventions
  • Elucidate the CF airways microbiome to test new paradigms of polymicrobial infection
  • Develop and standardize sensitive outcome measures for CFTR and airway function for upcoming CFTR potentiator and corrector trials
  • Establish and provide a pipeline for rapid preclinical evaluation of novel therapeutic strategies
  • Elucidate epigenetic programming in CF

Cystic Fibrosis:  Selected Publications from DZL Faculty Members Published Since 2010

Fritzsching B, Zhou-Suckow Z, Trojanek JB, Schubert SC, Schatterny J, Hirtz S, Agrawal R, Muley T, Kahn N, Sticht C, Gunkel N, Welte T, Randell SH, Länger F, Schnabel P, Herth FJ, Mall MA. Hypoxic Epithelial Necrosis Triggers Neutrophilic Inflammation via IL-1 Receptor Signaling in Cystic Fibrosis Lung Disease. Am J Respir Crit Care Med. 2015 Jan 21. [Epub ahead of print].

Hector A, Schäfer H, Pöschel S, Fischer A, Fritzsching B, Ralhan A, Carevic M, Öz H, Zundel S, Hogardt M, Bakele M, Rieber N, Riethmueller J, Graepler-Mainka U,Stahl M, Bender A, Frick JS, Mall M, Hartl D. Regulatory T Cell Impairment in Cystic Fibrosis Patients with Chronic Pseudomonas Infection. Am J Respir Crit Care Med. 2015 Jan 29. [Epub ahead of print].

Hilker R, Munder A, Klockgether J, Losada PM, Chouvarine P, Cramer N, Davenport CF, Dethlefsen S, Fischer S, Peng H, Schönfelder T, Türk O, Wiehlmann L, Wölbeling F, Gulbins E, Goesmann A, Tümmler B. Interclonal gradient of virulence in the Pseudomonas aeruginosa pangenome from disease and environment. Environ Microbiol. 2015;17:29-46.

Gehrig S, Duerr J, Weitnauer M, Wagner CJ, Graeber SY, Schatterny J, Hirtz S, Belaaouaj A, Dalpke AH, Schultz C, Mall MA. Lack of neutrophil elastase reduces inflammation, mucus hypersecretion, and emphysema, but not mucus obstruction, in mice with cystic fibrosis-like lung disease. Am J Respir Crit Care Med. 2014;189:1082-92.

Moura-Alves P, Faé K, Houthuys E, Dorhoi A, Kreuchwig A, Furkert J, Barison N, Diehl A, Munder A, Constant P, Skrahina T, Guhlich-Bornhof U, Klemm M, Koehler AB, Bandermann S, Goosmann C, Mollenkopf HJ, Hurwitz R, Brinkmann V, Fillatreau S, Daffe M, Tümmler B, Kolbe M, Oschkinat H, Krause G, Kaufmann SH. AhR sensing of bacterial pigments regulates antibacterial defence. Nature. 2014;512:387-92.

Stanke F, van Barneveld A, Hedtfeld S, Wölfl S, Becker T, Tümmler B. The CF-modifying gene EHF promotes p.Phe508del-CFTR residual function by altering protein glycosylation and trafficking in epithelial cells. Eur J Hum Genet. 2014;22:660-6.

Wielpütz MO, Puderbach M, Kopp-Schneider A, Stahl M, Fritzsching E, Sommerburg O, Ley S, Sumkauskaite M, Biederer J, Kauczor HU, Eichinger M, Mall MA. Magnetic resonance imaging detects changes in structure and perfusion, and response to therapy in early cystic fibrosis lung disease. Am J Respir Crit Care Med. 2014;189:956-65.

Anagnostopoulou P, Riederer B, Duerr J, Michel S, Binia A, Agrawal R, Liu X, Kalitzki K, Xiao F, Chen M, Schatterny J, Hartmann D, Thum T, Kabesch M, Soleimani M, Seidler U, Mall MA. SLC26A9-mediated chloride secretion prevents mucus obstruction in airway inflammation. J Clin Invest. 2012;122:3629-34.

Gehrig S, Mall MA, Schultz C. Spatially resolved monitoring of neutrophil elastase activity with ratiometric fluorescent reporters. Angew Chem Int Ed Engl.2012 Jun 18;51(25):6258-61.

Wiehlmann L, Cramer N, Ulrich J, Hedtfeld S, Weissbrodt H, Tümmler B. Effective prevention of Pseudomonas aeruginosa cross-infection at a cystic fibrosis centre - results of a 10-year prospective study. Int J Med Microbiol. 2012;302:69-77.