Carcinoma, Squamous Cell; Dermis; Fibroblasts; Keloid; Melanoma; Regenerative Medicine; Scleroderma, Systemic; Skin; Stem Cell Niche
The skin serves as a protective barrier against environmental insults and loss of essential body fluids, and has a remarkable ability to regenerate throughout life, which depends on self-renewal of epidermal stem cells and differentiation of their progeny. Stem cell fate decisions are determined by cell intrinsic mechanisms but also by the microenvironment. My group aims at dissecting how fibroblasts of the underlying dermis regulate these fate decisions. Importantly, skin fibroblasts are not, as previously thought, a homogeneous cell population. Instead they arise from two distinct lineages during embryonic development with unique functions in skin development, homeostasis and regeneration. When skin tumours arise from neoplastic epidermal cells, they elicit profound and distinct changes in the dermis. Our studies are shedding light on the important issue of how signature oncogenic mutations in epithelial cells reprogram fibroblasts to cancer-associated fibroblasts (CAFs) and result in characteristic stromal responses, and if the two distinct fibroblast lineages have unique functions in skin tumour development and progression. In addition, we aim to address the role of the distinct fibroblast lineages and dermal signalling in wound healing and fibroblast-mediated skin pathologies such as scleroderma and keloids, which lack an effective clinical treatment regimen.
Techniques, methods & infrastructure
The experimental strategies to address our research interests include state-of-the-art cell and molecular biology methods, in vivo lineage tracing techniques, next generation sequencing, and conditional knock-out mice or murine skin disease models.
- Functional Deconstruction of Fibroblast Heterogeneity in Malignant Skin Cancer (2018)
Source of Funding: OeNB (Oesterreichische Nationalbank), Anniversary Fund
- Functional Deconstruction of Fibroblast Heterogeneity in Skin Cancer (PhD fellowship to Sophie Frech) (2017)
Source of Funding: OeAW (Austrian Academy of Sciences), DOC
- CAFs - Paving The Way For New Cancer Therapies (2016)
Source of Funding: FWF (Austrian Science Fund), Elise Richter Programme
- FEBS Follow-up Research Award (2016)
Source of Funding: FEBS (Federation of European Biochemical Societies), Follow-up Research Fund
- Korosec, A. et al., 2019. Lineage Identity and Location within the Dermis Determine the Function of Papillary and Reticular Fibroblasts in Human Skin. Journal of Investigative Dermatology, 139(2), pp.342-351. Available at: http://dx.doi.org/10.1016/j.jid.2018.07.033.
- Lichtenberger, B.M., Mastrogiannaki, M. & Watt, F.M., 2016. Epidermal β-catenin activation remodels the dermis via paracrine signalling to distinct fibroblast lineages. Nature Communications, 7(1). Available at: http://dx.doi.org/10.1038/ncomms10537.
- Mastrogiannaki, M. et al., 2016. β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis. Journal of Investigative Dermatology, 136(6), pp.1130-1142. Available at: http://dx.doi.org/10.1016/j.jid.2016.01.036.
- Driskell, R.R. et al., 2013. Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature, 504(7479), pp.277-281. Available at: http://dx.doi.org/10.1038/nature12783.
- Lichtenberger, B.M. et al., 2010. Autocrine VEGF Signaling Synergizes with EGFR in Tumor Cells to Promote Epithelial Cancer Development. Cell, 140(2), pp.268-279. Available at: http://dx.doi.org/10.1016/j.cell.2009.12.046.