The Schlunck Lab – Cellular Signal Integration and Mechanobiology
Most diseases arise from changes in distinct cellular functions and novel therapeutic approaches allow to address specific molecular pathways. Therefore, it is our goal to characterize disease mechanisms and normal cellular functions on a molecular level to provide us with possible targets for improved treatment strategies.
Cells integrate a vast array of chemical, electrical and mechanical signals which in concert determine cell differentiation and function. We focused on the interplay of cell-ECM interactions and growth factor signaling with a special interest in mechanotransduction.
In this endeavour, we introduced the concept to use ROCK inhibitors (Meyer-ter-Vehn et al., 2006) or statins (Meyer-ter-Vehn et al., 2008) in scarring modulation following glaucoma surgery. With regard to intraocular pressure regulation and changes in primary open angle glaucoma, we provided the first reports on effects of extracellular matrix elasticity on human trabecular meshwork cells (Schlunck et al., 2008) and its influence on responses to TGF-β stimulation (Han et al., 2011). To allow for further insight into to the possible roles of small RNAs in the aqueous humor, we provided a first report on miRNA transcriptome data retrieved from single aqueous humor samples using Next Generation Sequencing (NGS) (Wecker et al., 2016).
Projects
Distinct Cell-Matrix Interactions
ECM degradation has a role in cell signaling, ECM remodeling and cell migration. Enzymatic ECM digestion allows tumor cells to infiltrate tissue and to evade the primary tumor site. However, localized ECM digestion appears to have a general role in tissue remodelling and repair. We study the effects of TGF-β on invadopodia, distinct subcellular ECM digestion sites, in human trabecular meshwork cells to gain further insight into possible mechanisms of glaucoma-associated structural changes in the ocular outflow tract.
Elasticity-Dependent Mechanotransduction
We have joined forces with collaborators in the fields of material science and engineering to develop novel cell culture substrata with tunable mechanical features. This project was initiated with support by the German Ministry of Education and Research (BMBF) and has allowed us to create novel, ultrasoft magnetoactive elastomers.
Novel Layers of Signal Integration – small RNAs
Signal integration is key to cell differentiation and survival. Small RNAs emerged as major modulators of gene expression with important implications in tissue homeostasis and disease. We strive to understand mechanisms of small RNA regulation by growth factor signaling and mechanotransduction to gain further insight into the pathophysiology of diverse eye diseases such as glaucoma or AMD.
Prof. Dr. med. Günther Schlunck
Guenther.Schlunck@uniklinik-freiburg.de
Team Members
- René Pöttke, Technical Assistant
- Dr. Moritz Gläser, MD
- Dr. Cornelius Wiedenmann, MD
- Emma Bungert, MD student
- Kosovare Zeqiri, MD student
- Charlotte Gottwald, MD student
- Janne Frömmichen, MD student
- Jeanne Ströble, MD student