Staab-Weijnitz Lab

Our work aims at unravelling the contributions of the extracellular matrix (ECM), in particular of collagen, on the regulation of dynamic cell circuits, on environmental barrier immunity, and on immunometabolic programming.

The extracellular matrix (ECM) is a ubiquitous complex glycoprotein network, which provides a scaffold for cellular support and migration and a mechanical barrier in all tissue types and compartments including the lung (see Figure 1). In addition, the ECM governs cell behavior and function by virtue of distinct biomechanical and molecular cues. Its components as well as ECM-modifying factors are secreted by multiple cell types including lung epithelial cells, lung fibroblasts, and immune cells. Hence, the ECM underlies constant remodeling and is drastically changed in chronic lung disease.

Figure 1 (Source: Claudia Staab-Weijnitz, Helmholtz Zentrum München): 
Immunofluorescent staining of a normal human lung section for type IV collagen (green). A, alveolar lumen; BEpi, bronchial epithelium; BL, bronchial lumen; Endo; endothelial layer; IM, interstitial matrix; sb BM, subbronchial basement membrane; SM, smooth muscle layer; V, inside of a vessel.

Collagen is the main ECM component in virtually all tissues. There are at least 28 different collagen types, which are sub-classified in seven categories (fibrillar, membrane, network-forming, beaded-filament forming, anchoring fibrils, multiplexins, and FACITs), based on their heterogeneous supramolecular structures. In addition, collagen chains are heavily modified by an intracellular protein machinery prior to secretion, as well as further processed, modified, and cross-linked by enzymatic and non-enzymatic events in the extracellular space (see Figure 2). Given the high abundance of collagen and the drastic changes in disease, it is of critical importance to decipher how changes in collagen composition and post-translational modification (PTM) patterns affect adhesion, migration and function of cells in normal physiology, in the context of environmental injury, and in lung disease.

Figure 2 (Source: Claudia Staab-Weijnitz, Helmholtz Zentrum München): 
Collagen biosynthesis and extracellular processing exemplified by type I collagen. For more details, please refer to Onursal et al, Front Med, 2021 (doi.org/10.3389/fmed.2021.593874)

Ultimately, we aim to:

  • Define environmentally triggered and lung disease-specific changes in biosynthesis and molecular properties of collagen
  • Characterize the functional impact of altered collagen composition and properties on adherent and migrating cells with emphasis on progenitor and immune cells in the lung
  • Translate these findings into novel prognostic, diagnostic, and therapeutic strategies in lung disease

In order to reach this aim, we have to:

  • Set up an experimental and bioinformatics pipeline to characterize changes of the ECM and in particular of collagen chains and PTMs on molecular level
  • Work with human organotypic in vitro models of lung injury and repair for analysis of ECM changes and how they affect proliferation, migration, and differentiation of adherent cells
  • Profile clinical samples for altered expression of ECM and ECM regulators as well as peripheral markers of collagen formation and degradation

ORCID-ID: 0000-0002-1211-7834 (http://orcid.org/0000-0002-1211-7834