Universiteit Leiden

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Research project

Systems dermatology of immune-mediated dermatological diseases: cutaneous T-cell lymphoma

The complex pathophysiology of immuno-dermatological disorders is multifactorial, including environmental, skin microbiome, (epi)genetic and immune dysregulation conditions. This project primarily focuses on the orphan disease mycosis fungoides, a subtype of cutaneous T-cell lymphoma. The current pathophysiological understanding of this extremely rare malignancy remains limited. Therefore, there is a high unmet medical need, urgently requiring the elucidation of the mechanistic basics by means of systems pharmacology/dermatology. One common contributing factor in many dermatological diseases, including mycosis fungoides, is an altered cutaneous lipid composition and organization entailing a perturbed skin barrier. Thus, we hypothesize that the in-depth characterization and understanding of the cutaneous barrier will yield important insights for both the pathophysiology and clinical practice of the individual patient. This project aims to analyze the lipid composition characteristics of the dysfunctional skin barrier and to elucidate skin morphology, as well as molecular and cellular-immunological properties. To this end, a structural study of the skin barrier lipid composition in patients and healthy controls will be performed using various techniques, including high-resolution lipidomics. Additionally, the role of lipids as minimally invasive biomarkers will be assessed by correlating them to disease diagnosis, disease severity, and progression. These novel biomarkers would constitute an important tool for early diagnosis and disease monitoring of cutaneous T-cell lymphoma and could ultimately be applied to other immune-mediated skin diseases with similar underlying mechanisms.

Catherine Mergen
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