Journal article
Spatial proteomics identifies JAKi as treatment for a lethal skin disease
TM Nordmann, H Anderton, A Hasegawa, L Schweizer, P Zhang, PC Stadler, A Sinha, A Metousis, FA Rosenberger, M Zwiebel, TK Satoh, F Anzengruber, MT Strauss, MC Tanzer, Y Saito, T Gong, M Thielert, H Kimura, N Silke, EH Rodriguez Show all
Nature | Published : 2024
Open access
Abstract
Toxic epidermal necrolysis (TEN) is a fatal drug-induced skin reaction triggered by common medications and is an emerging public health issue1–3. Patients with TEN undergo severe and sudden epidermal detachment caused by keratinocyte cell death. Although molecular mechanisms that drive keratinocyte cell death have been proposed, the main drivers remain unknown, and there is no effective therapy for TEN4–6. Here, to systematically map molecular changes that are associated with TEN and identify potential druggable targets, we utilized deep visual proteomics, which provides single-cell-based, cell-type-resolution proteomics7,8. We analysed formalin-fixed, paraffin-embedded archived skin tissue ..
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Awarded by State Government of Victoria
Funding Acknowledgements
The authors thank all members of the Proteomics and Signal Transduction group at the Max Planck Institute of Biochemistry, especially K. Zettl for immunofluorescence staining, B. Splettstoesser for cell culture and S. Steigerwald, G. Wallmann and T. Heymann for mass spectrometry method optimizations; K. Kerl-French for revalidation of all cases; and L. Zeitler and P. P. Ogger for technical assistance for the live-cell imaging experiments. The J2/3T3 cells were a gift from H.-D. Beer. This study was supported by the Max Planck Society for Advancement of Science. T.M.N. is supported by a Swiss National Science Foundation (SNSF) Early Postdoc Mobility (P2ZHP3-199648) and Postdoc Mobility Fellowship (P500PM_210917). J.S., H.A. and N.S. are supported by NHMRC grants Investigator Grant (1195038 and 1194144) and through the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS (GNT9000719).