PhD Scientific Days 2026

Poster Session 1.S - Conservative Medicine

Identification of Novel Regulators of the Keratinocyte CBM Complex in Psoriasis

Name of the presenter

Szabolcs, Botond

Institute/workplace of the presenter

Department of Phisiology, Department of Dermatology, Venereology and Dermatooncology

Authors

Botond Szabolcs¹, Alexandra Lakatos², Dorottya Pál², Katalin Buday², Marianna Nagy-Schwedtner², Zsuzsanna Kurgyis³, Lajos V Kemény¹
1: Department of Dermatology, Venereology and Dermatooncology, Department of Phisiology, SE
2: Department of Phisiology, SE
3: Technical University of Munich, Depratment of Dermatology and Allergology

Text of the abstract

Introduction
Psoriasis is a chronic inflammatory skin disease affecting more than 125 million people worldwide. The lesions develop in a remitting-relapsing manner and triggered by poorly defined mechanisms. The triggering factors can be sensed by either immune cells or keratinocytes. The CBM complex, which includes CARD14, BCL10, and MALT1, plays a key regulatory role in keratinocyte cytokine responses and has been associated with clinically similar inflammatory skin disorders. However, the regulation of CBM complex activity remains unclear.
Aim
Our aim was to identify physiological regulators of the CBM complex that may serve as novel therapeutic targets in psoriasis.
Methods
Our group previously demonstrated that BCL10 activity correlates with CBM complex function. Using the DepMap database, which enables analysis of the viability effects of knocking out 18,000 genes across 1,070 cancer cell lines, we correlated genetic dependencies of cell lines with their sensitivity to BCL10 knockout. This approach allowed us to identify genes potentially involved in the same signaling pathways as BCL10, and therefore candidate regulators of the CBM complex. We prioritized genes that have shown association with psoriasis in GWAS studies. ClueGO pathway analysis was made on significant genes.
Result
Our analysis identified 58 genes whose knockout significantly correlated (p <0.05, FDR <0.25, r > 0.2) with BCL10 knockout. Among the top correlating genes were MALT1 and CARD14, suggesting that our analysis successfully identified key known components of the CBM pathway. Furthermore, several genes associated with psoriasis in GWAS datasets also showed significant correlation with BCL10 dependency. ClueGO analysis revealed that genes correlated with BCL10 dependency are involved in over 100 signaling pathways, including known biological pathways involved in psorasis such as nfkb signalling.
Conclusion
Using our approach, we identified several genes that may act as regulators or activators of the CBM complex and could play a role in psoriasis pathogenesis. Future studies will focus on validating these findings through in vitro and in vivo experiments to identify potential therapeutic targets.
Funding
OTKA FK138696
MTA-SE Lendület "Momentum” Dermatooncology Research Group (LP2024-12/2024).
Grant agreement No 739593 of the EU Horizon 2020.