adverse cutaneous drug reactions, cancer-drug induced skin reactions, innate and adaptive immunity, lichenoid skin inflammation
What we investigate
Our laboratory studies the innate and adaptive immune pathways leading to lichenoid skin reactions including the frequent inflammatory skin disease Lichen planus and drug-induced lichenoid reactions (e.g. by checkpoint inhibition), as well as leading to other severe adverse drug reactions of the skin. The goal of our research is to open up new relevant research avenues and to identify new therapeutic targets in difficult-to-treat diseases.
Our research in more detail
Inflammatory skin diseases are frequent in number and often lead to a decreased quality of life in the affected patients. Lichenoid inflammation is one of the most commonly encountered inflammation patterns of the skin. The prototypical lichenoid mucocutaneous disease is Lichen planus (LP) with its several subtypes. Cell-mediated cytotoxicity is regarded as a major pathomechanism of LP, thereby resembling artificial lichenoid skin reactions (ALSR) induced by immune checkpoint inhibitors. However, the exact pathophysiology remains unclear. Our laboratory demonstrated distinct gene expression patterns between the different forms of LP and ALSR, underlining the need of a detailed investigation of molecular pathways of LP and ALSR. We aim to characterize the different forms of LP and ALSR, using integrated transcriptomic profiling with surface proteomics on a single cell level, high-dimensional single-cell analysis using Time of Flight Mass Cytometry, followed by the investigation of the molecular mechanism using state-of-the-art-techniques for gene modification such as CRISPR-Cas9 in three-dimensional skin-equivalent models. The aim of our research is to identify key molecules as targets for future therapies of these difficult-to-treat skin diseases.
SKINTEGRITY.CH Principal Investigators are underlined:
Stäger R, Stanhope S, Greenshields-Watson A, Collins L, Ramelyte E, Kolm I, Dummer R, Meier-Schiesser B (2021): Demonstration of T cell redirection and immune activation in skin rash following tebentafusp treatment. Annals of Oncology 32:S1215. https://doi.org/10.1016/j.annonc.2021.08.1716
Meier-Schiesser B, Mellett M, Ramirez-Fort MK, Maul J-T, Klug A, Winkelbeiner N, Fenini G, Schafer P, Contassot E and French LE (2021). Phosphodiesterase-4 inhibition reduces cutaneous inflammation and IL-1β expression in a psoriasiform mouse model but does not inhibit inflammasome activation. Int J Mol Sci, 22(23):12878. https://doi.org/10.3390/ijms222312878
Satoh TK, Mellett M, Meier-Schiesser B, Fenini G, Otsuka A, Beer HD, Rordorf T, Maul JT, Hafner J, Navarini AA, Contassot E and French LE (2020). Skin toxicity to EGFR/MEK inhibitor cancer therapy is mediated by IL-36γ and requires the skin commensal Propionibacterium acnes. J Clin Invest, 130(3):1417-1430. https://doi.org/10.1172/JCI128678
Meier-Schiesser B, Feldmeyer L, Jankovic D, Mellett M, Satoh TK, Yerly D, Navarini AA, Abe R, Yawalkar N, Chung WH, French LE and Contassot E (2019). Culprit drugs induce specific IL-36 overexpression in Acute Generalized Exanthematous Pustulosis J Invest Dermatol, 139(4):848-858. https://doi.org/10.1016/j.jid.2018.10.023