What we investigate

Our laboratory studies the molecular and cellular mechanisms of skin inflammation, with a special focus on the vascular system and other stromal cells. We apply global and single cell transcriptomics and epigenetic screens on distinct cell types isolated from clinical lesions and advanced inflammatory disease models.

KEYWORDS
epigenetics, fibroblasts, psoriasis, skin inflammation, therapy

Cultured human dermal lymphatic endothelial cells stained for the transcription factor Prox1 <em>(green)</em> and the adhesion molecule CD31 <em>(red)</em>.
Cultured human dermal lymphatic endothelial cells stained for the transcription factor Prox1 (green) and the adhesion molecule CD31 (red).
Our research in more detail

Epigenetic regulation plays an important role in epidermal development, regeneration, differentiation and cancer. There is strong evidence that also stromal cells, including fibroblasts and endothelial cells, undergo epigenetic changes in chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. However, the potential role of epigenetic changes in stromal cells with regard to skin inflammation has remained unclear, even though we and others found that several in vitro functions of fibroblasts isolated from psoriatic plaques differ from healthy fibroblasts even after several passages in culture. We use clinical psoriatic skin samples and experimental psoriasis models to isolate specific stromal cell types and to validate potential hits by expression analyses and treatment studies. In our research, we aim to define the global and single cell transcriptome and epigenome of healthy and diseased cells in vitro and ex vivo. Elucidating the transcriptional and epigenetic regulation of stromal cells in psoriasis might provide new insights into the control of the stromal memory in inflammation. We also investigate the effects of lymphatic vessel activation on skin inflammation and wound repair, using a newly developed therapeutic agent. Our studies indicate that pro-lymphangiogenic therapies might represent a new strategy for the treatment of inflammatory skin diseases.

 
Prof. Michael Detmar


Prof. Michael Detmar
ETH Zurich
Institute of Pharmaceutical Sciences
Vladimir-Prelog-Weg 3
8093 Zurich

Email   Website

Selected publications

SKINTEGRITY.CH Principal Investigators are in bold:

  • Schwager, S., Renner, S., Hemmerle, T., Karaman, S., Proulx, S.T., Fetz, R., Golding-Ochsenbein, A.M., Probst, P., Halin, C., Neri, D., and Detmar, M. (2018). Antibody-mediated delivery of VEGF-C potently reduces chronic skin inflammation. JCI Insight 3: e124850.
  • He, Y., Kim, J., Tacconi, C., Moody, J., Dieterich, L. C., Anzengruber, F., Maul, J.-T., Gousopoulos, E., Restivo, G., Levesque, M.P., Lindenblatt, N., Shin, J.W., Hon, C.-C., & Detmar, M.(2022). Mediators of capillary-to-venule conversion in the chronic inflammatory skin disease psoriasis. J Invest Dermatol, 142: 3313-3326
  • He,Y., Tacconi, C., Dieterich, L.C., Kim, J., Restivo, G., Gousopoulos, E., Lindenblatt, N., Levesque, M.P., Claassen, M., & Detmar, M.(2022). Novel blood vascular endothelial subtype-specific markers in human skin unearthed by single-cell transcriptomic profiling. Cells, 11(7), 1111
  • Kim, J., He, Y., Tormen, S., Kleindienst, P., Restivo, G., Drach, M., Levesque, M.P., Navarini, A.A., Tacconi, C., & Detmar, M.(2022) The p300/CBP inhibitor A485 normalizes psoriatic fibroblast gene expression in vitro and reduces psoriasis-like skin inflammation in vivo. J Invest Dermatol, JID 3571
  • Brunner, L.M., He, Y., Cousin, N., Scholl, J., Albin, L.K., Schmucki, B., Supersaxo, S., Restivo, G., Hafner, J., Neri, D., Werner, S.& Detmar, M. (2023). Promotion of lymphangiogenesis by targeted delivery of VEGF-C improves diabetic wound healing. Cells, 12(3), 472