Prof. Michael Detmar

Keywords

Epigenetics, Fibroblasts, Psoriasis, Skin Inflammation, Therapy

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.

Our research in more detail

Abbildung Werner
Cultured human dermal lymphatic endothelial cells stained for the transcription factor Prox1 (green) and the adhesion molecule CD31 (red).

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. Thus far, we have established a large number of primary cultures of dermal fibroblasts, blood vascular cells and lymphatic endothelial cells. We aim to define the global and single cell transcriptome and epigenome of healthy and diseased cells in vitro and ex vivo and to perform epigenetic drug screens. Elucidating the transcriptional and epigenetic regulation of stromal cells in psoriasis might provide new insights into the control of the stromal memory in inflammation, and might open up the possibility to develop specific epigenetic drug treatments for psoriasis.

Selected publications

SKINTEGRITY.CH Principal Investigators are underlined:

  • Gousopoulos E, Proulx ST, Bachmann SB, Scholl J, Dionyssiou D, Demiri E, Halin C, Dieterich LC and Detmar M (2016). Regulatory T cell transfer ameliorates lymphedema and promotes lymphatic vessel function. JCI Insight 1: e89081.
  • Schwager S, Renner S, Hemmerle T, Karaman S, Proulx ST, Fetz R, Golding-Ochsenbein AM, 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.
  • Polomska A, Proulx ST, Brambilla D, Fehr D, Bonmarin M, Brändli S, Meboldt M, Steuer C, Vasileva T, Reinke N, Leroux JC and Detmar M (2019) Minimally invasive method for the point-of-care quantification of lymphatic vessel function. JCI Insight 4: e126515
  • Dieterich LC, Tacconi C, Menzi F, Proulx ST, Kapaklikaya K, Hamada M, Takahashi S and Detmar M (2020). Lymphatic MAFB regulates vascular patterning during developmental and pathological lymphangiogenesis. Angiogenesis 23, 411-423.
  • Fujimoto N, He Y, D`Addio M, Tacconi C, Detmar M* and Dieterich LC* (2020). Single-cell mapping reveals new markers and functions of lymphatic endothelial cells in lymph nodes. PLoS Biol 18: e3000704.  *Joint corresponding authors.