Research Field
Nanomedicine
Title
Identification of novel compounds for Wnt/β-catenin induced lung repair
in COPD
Description
Chronic obstructive pulmonary disease (COPD) is an incurable disease,
characterized by a progressive loss of lung tissue. Current therapeutic
approaches can only provide symptomatic relief. Wnt/β-catenin
signaling has been described as a potential pathway involved in lung
repair and regeneration. We recently showed that Wnt/β-catenin is
decreased in COPD/emphysema and that both in vivo (in an elastaseinduced mouse model of emphysema) and ex vivo (in 3D human and
mouse lung tissue slices) pharmaceutical activation attenuated the
disease (eg. decreases in MMP12 and elastin). Our aim is to identify
novel lung regenerative compounds. To this end, we are currently
conducting a high-throughput drug screen in order to find novel Wnt/βcatenin activator. In order to characterize the effect of candidate drugs,
we aim to use multifunctional mesoporous silica nanoparticles (MSNs),
which can be utilized for bioimaging of pathological/regenerative
processes in lung tissue.
The student contributing to this project will:
Characterize the effect of candidate drugs using a readout closely
related to disease pathomechanism:
- measurement in in vitro cell culture and ex vivo 3D lung tissue slices
of MMP12 protease activity using avidin-capped MSN, loaded with
fluorescent dyes and functionalized with linkers specifically cleaved by
MMP12
Generate and process 3D lung tissue slices
Be part of a translational research project and learn more about
chronic lung diseases
1. Kneidinger, N., et al. (2011). "Activation of the WNT/beta-catenin pathway attenuates
experimental emphysema." Am J Respir Crit Care Med 183(6): 723-733.
2. Uhl, F. E., et al. (2015). "Preclinical validation and imaging of Wnt-induced repair in human 3D
lung tissue cultures." Eur Respir J 46(4): 1150-1166.
3. van Rijt, S. H., et al. (2015). "Protease-mediated release of chemotherapeutics from mesoporous
silica nanoparticles to ex vivo human and mouse lung tumors." ACS Nano 9(3): 2377-2389.
Supervisor
Dr. Melanie Königshoff & Dr. Darcy Wagner
Research Mentor
Rita Costa, PhD Student
Department
Comprehensive Pneumology Center (CPC), Helmholtz Zentrum München
and University Hospital of the Ludwig Maximilian University
Website
http://www.cpc-munich.org