PhD Scientific Days 2025

Poster Session III. - X: Conservative Medicine

Identification of novel members and regulators of the keratinocyte CARD/BCL10/MALT1 signaling pathway

Name of the presenter

Szabolcs Botond

Institute/workplace of the presenter

Department of Phisiology, Department of Dermatology, Venereology and Dermatooncology

Authors

Szabolcs Botond¹, Pál Dorottya¹, Lakatos Alexandra¹

1: Department of Phisiology

Text of the abstract

Introduction
Psoriasis is a chronic inflammatory skin disease affecting over 125 million people worldwide. Lesions develop in a remitting-relapsing pattern triggered by poorly defined mechanisms sensed by immune cells or keratinocytes. The CBM complex, which includes CARD14, BCL10, and MALT1, plays a key role in keratinocyte cytokine responses and is linked to related inflammatory skin disorders. However, regulation of CBM complex activity remains unclear.

Aim
We aimed to identify physiological regulators of the CBM complex that may serve as novel therapeutic targets in psoriasis.

Methods
Our group previously showed that BCL10 activity correlates with CBM complex function. Using the DepMap database, which assesses viability effects of knocking out 18,000 genes across 1,070 cancer cell lines, we correlated genetic dependencies with BCL10 knockout sensitivity. This approach identified genes potentially involved in the same pathways as BCL10 and candidate regulators of the CBM complex. Genes associated with psoriasis in GWAS studies were prioritized. Significant genes underwent ClueGO pathway analysis.

Results
We 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, confirming successful identification of known CBM components. Several psoriasis-associated GWAS genes also showed significant correlation with BCL10 dependency. ClueGO analysis revealed that these genes participate in over 100 pathways, including psoriasis-related NF-κB signaling.

Conclusion
Our findings suggest that, beyond MALT1 and CARD14, BCL10 function is linked to multiple genes involved in psoriasis development. These may represent physiological CBM complex regulators with key roles in psoriasis pathogenesis. We plan to validate these findings through in vitro and in vivo studies to identify new therapeutic targets.

Funding
OTKA FK138696
MTA-SE Lendület "Momentum” Dermatooncology Research Group (LP2024-12/2024)
Grant agreement No 739593 of the EU Horizon 2020