SkinChronicles, No 9, January 2026, by Lavanya Moparthi

Mass spectrometry–based spatial proteomics is an emerging approach that provides deeper molecular insights into biological processes at single‑cell resolution in situ.

Nordmann and colleagues have advanced spatial proteomics by developing deep visual proteomics (DVP), enabling the identification of disease-specific molecular signatures in defined cell types from formalin-fixed paraffin-embedded tissue sections of patients with mild and severe cutaneous adverse drug reactions (CADRs). Remarkably, these findings were swiftly translated into clinical practice to treat the fatal skin disease, toxic epidermal necrolysis (TEN).

This innovative approach integrates high-content imaging, AI-based cell segmentation and classification, laser microdissection, and ultrasensitive mass spectrometry-based proteomics. Using this strategy, the authors identified upregulation of the JAK/STAT pathway in both keratinocytes and cutaneous immune cells in TEN, but not in mild CADRs such as maculopapular rash.

Furthermore, the effect of JAK/STAT inhibition on TEN severity was confirmed using both in vitro cell-based models and in vivo in mouse models, establishing that the JAK/STAT pathway is a primary determinant of the disease. Finally, based on these compelling preclinical findings, seven patients with TEN were successfully treated with a JAK inhibitor.

Another spatial proteomics study by Møller and colleagues identified upregulation of the cholesterol biosynthesis pathway, particularly in the inner dermis of lesional skin from psoriasis patients. These findings highlight the cholesterol pathway as a potential target for new therapeutic interventions.

Considering my interest in the molecular pathways underlying hyperproliferative skin diseases such as psoriasis, atopic dermatitis and squamous cell carcinoma, this cutting-edge method could be highly valuable for addressing my research questions.

References

1. Nordmann TM, Anderton H, Hasegawa A, Schweizer L, Zhang P, Stadler PC, Sinha A, Metousis A, Rosenberger FA, Zwiebel M, Satoh TK, Anzengruber F, Strauss MT, Tanzer MC, Saito Y, Gong T, Thielert M, Kimura H, Silke N, Rodriguez EH, Restivo G, Nguyen HH, Gross A, Feldmeyer L, Joerg L, Levesque MP, Murray PJ, Ingen-Housz-Oro S, Mund A, Abe R, Silke J, Ji C, French LE, Mann M. Spatial proteomics identifies JAKi as treatment for a lethal skin disease. Nature. 2024 Nov;635(8040):1001-1009.
2. Møller LBP, Kromann B, Kabatnik S, Hjortlund JH, Haulrig MB, Sølberg JBK, Bzorek M, Clark RA, Skov L, Mann M, Løvendorf MB, Dyring-Andersen B. Spatial Proteomic Profiling Reveals Increased Levels of Cholesterol Synthesis Proteins in Psoriasis Vulgaris. J Invest Dermatol. 2025 Dec;145(12):3051-3063.e2.