Carsten Schultz and Marcus Mall
MMPU Group 2006 – 2018
Project Summary
The focus of this project is on the pathogenesis and treatment of cystic fibrosis (CF) lung disease, one of the most common lethal hereditary diseases in Caucasians. We use an interdisciplinary approach combining chemical biology and in vivo analyses of genetically engineered mouse models to advance our current understanding of the pathogenesis, identify novel biomarkers and develop efficient therapeutic strategies for CF lung disease. The long term goal of this project is the translation of the results from pre-clinical models into the clinic.
Background
Marcus Mall has studied the basic ion transport defect in cystic fibrosis (CF) airways and developed a transgenic mouse model of CF lung disease. Carsten Schultz developed small molecule compounds that target the CF ion transport defect, and fluorescent sensors to monitor enzyme activities and intracellular signaling events in living cells. They joined the MMPU in 2006 to coordinate their longstanding research interests in cystic fibrosis.
Selected publications
Maturation of the matrix and viral membrane of HIV-1.
Qu K, Ke Z, Zila V, Anders-Össwein M, Glass B, Mücksch F, Müller R, Schultz C, Müller B, Kräusslich HG, Briggs JAG. Science. 2021 Aug 6;373(6555):700-704. doi: 10.1126/science.abe6821. PMID: 34353956
IL-17A from innate and adaptive lymphocytes contributes to inflammation and damage in cystic fibrosis lung disease.
Hagner M, Albrecht M, Guerra M, Braubach P, Halle O, Zhou-Suckow Z, Butz S, Jonigk D, Hansen G, Schultz C, Dittrich AM, Mall MA.
Eur Respir J. 2020 Dec 10:1900716. doi: 10.1183/13993003.00716-2019. Online ahead of print.
PMID: 33303549
Protease FRET Reporters Targeting Neutrophil Extracellular Traps.
Guerra M, Halls VS, Schatterny J, Hagner M, Mall MA, Schultz C.
J Am Chem Soc. 2020 Nov 13. doi: 10.1021/jacs.0c08130. Online ahead of print. PMID: 33186023
New method for rapid and dynamic quantification of elastase activity on sputum neutrophils from patients with cystic fibrosis using flow cytometry.
Hagner M, Frey DL, Guerra M, Dittrich AS, Halls VS, Wege S, Herth FJF, Schultz C, Mall MA.
Eur Respir J. 2020 Apr 30;55(4):1902355. doi: 10.1183/13993003.02355-2019. Print 2020 Apr.
PMID: 32139467
Elastase Exocytosis by Airway Neutrophils Is Associated with Early Lung Damage in Children with Cystic Fibrosis.
Margaroli C, Garratt LW, Horati H, Dittrich AS, Rosenow T, Montgomery ST, Frey DL, Brown MR, Schultz C, Guglani L, Kicic A, Peng L, Scholte BJ, Mall MA, Janssens HM, Stick SM, Tirouvanziam R.
Am J Respir Crit Care Med. 2019 Apr 1;199(7):873-881. doi: 10.1164/rccm.201803-0442OC. PMID:30281324
Cathepsin G Activity as a New Marker for Detecting Airway Inflammation by Microscopy and Flow Cytometry.
Guerra M, Frey D, Hagner M, Dittrich S, Paulsen M, Mall MA, Schultz C.
ACS Cent Sci. 2019 Mar 27;5(3):539-548. doi: 10.1021/acscentsci.8b00933. Epub 2019 Feb 19. PMID:30937381
Chronic but not intermittent infection with Pseudomonas aeruginosa is associated with global changes of the lung microbiome in cystic fibrosis
Sébastien Boutin, Simon Y. Graeber, Mirjam Stahl, A. Susanne Dittrich, Marcus A. Mall, Alexander H. Dalpke
Eur Respir J. 2017 Oct 5;50(4). pii: 1701086. doi: 10.1183/13993003.01086-2017. Print 2017 Oct. PMID:28982777
Neutrophil elastase and matrix metalloproteinase 12 in cystic fibrosis lung disease.
Wagner CJ, Schultz C, Mall MA.
Mol Cell Pediatr. 2016 Dec;3(1):25. doi: 10.1186/s40348-016-0053-7. Epub 2016 Jul 25. Review
Airway Mucus Obstruction Triggers Macrophage Activation and MMP12-dependent Emphysema.
Trojanek JB, Cobos-Correa A, Diemer S, Kormann M, Schubert SC, Zhou-Suckow Z, Agrawal R, Duerr J, Wagner CJ, Schatterny J, Hirtz S, Sommerburg O, Hartl D, Schultz C, Mall MA.
Am J Respir Cell Mol Biol. 2014 Nov;51(5):709-20.
A new player in the game: epithelial cathepsin S in early cystic fibrosis lung disease.
Mall MA, Schultz C.
Am J Respir Crit Care Med. 2014 Jul 15;190(2):126-7. doi: 10.1164/rccm.201405-0935ED.
Lack of neutrophil elastase reduces inflammation, mucus hypersecretion and emphysema, but not mucus obstruction, in mice with CF-like lung disease.
Gehrig S, Duerr J, Weitnauer M, Wagner CJ, Graeber SY, Schatterny J, Hirtz S, Belaaouaj A, Dalpke AH, Schultz C, Mall MA.
Am J Respir Crit Care Med. 2014 Mar 28. [Epub ahead of print]
FRET-based and other fluorescent proteinase probes.
Hu HY, Gehrig S, Reither G, Subramanian D, Mall MA, Plettenburg O, Schultz C.
Biotechnol J. 2014 Feb;9(2):266-81. doi: 10.1002/biot.201300201. Epub 2014 Jan 27.
CFTR Regulates Early Pathogenesis of Chronic Obstructive Lung Disease in βENaC-Overexpressing Mice.
Johannesson B, Hirtz S, Schatterny J, Schultz C, Mall MA.
PLoS One. 2012;7(8):e44059. Epub 2012 Aug 24
mCLCA3 does not contribute to calcium-activated chloride conductance in murine airways. Mundhenk L, Johannesson B, Anagnostopoulou P, Braun J, Bothe MK, Schultz C, Mall MA, Gruber AD.
Am J Respir Cell Mol Biol. 2012 Jul;47(1):87-93. Epub 2012 Feb 23.
Spatially resolved monitoring of neutrophil elastase activity with ratiometric fluorescent reporters.
Gehrig S, Mall MA, Schultz C.
Angew Chem Int Ed Engl. 2012 Jun 18;51(25):6258-61. doi: 10.1002/anie.201109226. Epub 2012 May 3.
The ßENaC-overexpressing mouse as a model of cystic fibrosis lung disease
Zhou Z, Duerr J, Johannesson B, Schubert SC, Treis D, Harm M, Graeber SY, Dalpke A, Schultz C, Mall MA
J Cyst Fibros. 2011 Jun;10 Suppl 2:S172-82.
Airway surface liquid volume regulation determines different airway phenotypes in liddle’s compared to {beta}ENAC-overexpressing mice
Mall MA, Button B, Johannesson B, Zhou Z, Livraghi A, Caldwell RA, Schubert SC, Schultz C, O’Neal WK, Pradervand S, Hummler E, Rossier BC, Grubb BR, Boucher RC.
J Biol Chem. 2010 Jun 21
Reporters to monitor cellular MMP12 activity
Amanda Cobos-Correa, Marcus A. Mall, Carsten Schultz
Proc. SPIE 2010, Vol. 7576, 757605
Membrane-bound FRET probe visualizes MMP12 activity in pulmonary inflammation.
Cobos-Correa A, Trojanek JB, Diemer S, Mall MA, Schultz C.
Nat Chem Biol. 2009;5:628-30.
Group members
in alphabetical order
Raman Agrawal, PhD, Postdoc
Amanda Cobos-Correa, PhD
Stefanie Diemer, MD Student
Susanne Dittrich, MD, Physician Scientist
Dario Frey, PhD student (HBIGS)
Stefanie Gehrig, PhD Student, Postdoc
Matteo Guerra, PhD student (EMBL International PhD Programme – EIPP)
Nicole Heath, MD, Research Fellow
Stephanie Hirtz, Research Technician
Bjarki Johannesson, PhD Student
Markus Mall, MD
Group Leader
now: Head of the Department of Paediatrics, Division of Pneumology and Immunology at Charité University Hospital Berlin
Gregor Reither, PhD, Postdoc
Verena Rickert-Zacharias, PhD student (EMBL International PhD Programme – EIPP)
Susanne Schubert, PhD, Postdoc
Carsten Schultz, PhD
Group Leader
now: Chair of Physiology and Pharmacology at the Portland School of Medicine at OHSU (Oregon Health & State University)
Stephan Spahn, MD student (HBIGS, JCF HRCMM)
Frank Stein, PhD, Postdoc
Joanna Trojanek, PhD, Postdoc
Claudius Wagner, PhD student (HBIGS)
