Prof. Lars E. French

Keywords

Inflammation, adverse cutaneous drug reactions, innate immunity, cell death, tumor immunology.

What we investigate

Our research focus on severe cutaneous adverse drug reaction and inflammatory skin diseases. It spans from a preclinical molecular biology focusing on the identification and characterization of key molecules to a translational research with emphasis on therapeutic targets.

Our research in more detail

Abbildung French
Immunofluorescent staining with anti–IL-36γ (red) and anti-KLF4 (green) antibodies of acneiform eruption patients and healthy controls (HC). Nuclei were stained with DAPI. The white-boxed regions were zoomed separately in the right. (Satoh TK et al, J Clin Invest. 130(3):1417-1430)

The skin is an active immune organ equipped with variety of immune cells and sensors that act as a first line of innate defence against microbial pathogens and physical and chemical insults. In recent years it has become clear that innate immune responses within the skin are not only a first line of defence but also key to the pathogenic mechanisms of several inflammatory skin diseases. In our laboratory, we focus on understanding the pathogenesis of severe cutaneous adverse drug reactions and inflammatory skin diseases (mainly neutrophilic dermatoses) mediated by inappropriate skin-directed immune responses. To do this we use an unbiased approach making use of modern omics technologies to identify driver cytokines and key signalling pathways within biobanked specimens of inflammatory skin diseases. Further investigation and validation of leads is done using functional approaches investigated using biochemistry and cell biology in human cell culture models, ex vivo human skin culture models and in vivo mouse experiments. Using investigator initiated clinical trials and prospective patient registries (www.irten.org) novel therapeutic approaches are investigated in human disease.    

Selected publications

SKINTEGRITY.CH Principal Investigators are underlined:

  • Satoh TK, Mellett M, Meier-Schiesser B, Fenini G, Otsuka A, Beer H-D, Rordorf T, Maul JT, Hafner J, Navarini AA, Contassot E and French LE (2020). IL-36γ drives skin toxicity induced by EGFR/MEK inhibition and commensal Cutibacterium acnes. J Clin Invest. 130(3):1417-1430.
  • Mellett M, Meier B, Mohanan D, Schairer R, Cheng P, Satoh TK, Kiefer B, Ospelt C, Nobbe S, Thome M, Contassot E and French LE (2018). CARD14 Gain-of-Function Mutation Alone Is Sufficient to Drive IL-23/IL-17-Mediated Psoriasiform Skin Inflammation In Vivo. J Invest Dermatol. 138(9):2010-2023.
  • 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 (2018). Culprit Drugs Induce Specific IL-36 Overexpression in Acute Generalized Exanthematous Pustulosis. J Invest Dermatol. 139(4):848-858.
  • Fenini G, Grossi S, Gehrke S, Beer H-D, Satoh TK, Contassot E and French LE (2018). The p38 Mitogen-Activated Protein Kinase Critically Regulates Human Keratinocyte Inflammasome Activation. J Invest Dermatol. 138(6):1380-1390.