Epidermis, genetic syndromes, keratinocytes, skin tumor syndromes
What we investigate
Our laboratory analyzes genetic skin diseases to unravel the function of the affected genes/proteins. Since most genodermatoses are rare, and consequently access to biological material difficult, we develop in vitro human and mouse models to facilitate investigation of the biological pathways affected by the mutated gene/protein.
Our research in more detail
Actin Related Protein-Testis1 in Skin and Basal Cell Cancer
BCC is the most common malignant tumor in humans. ARP-T1 dysfunction causes Bazex Dupré Christol Tumor Syndrome characterized by epidermal dysplasia and BCC. We are interested in how ARP-T1 dysfunction by mutation alters cellular signaling and ultimately induces proliferation. We analyze whether and how ARP-T1 bridges between actin cytoskeleton organization involved in vesicle transport at the centrosome, the centrioles and the basal body and/or the formation of ciliary pocket in the transition zone of primary cilia.
The CYLD-CENPV axis
Spiegler-Brooke cylindromatosis syndrome is caused by mutations in the CYLD gene, a deubiquitinase regulating diverse signaling pathways. Since tumors of the pilo-sebaceous-apocrine unit primarily locate to sun exposed skin, we hypothesize that UV induced DNA and tissue damage are required to cause tumor formation. Notably, we identified several CYLD interactors, and one of them, TRAIP, is involved in the spindle assembly checkpoint and in DNA damage response. Another, CENPV, is a nuclear and microtubule binding protein localized at centromers. CENPV is found in cilia, cylindromas are ciliated and CYLD is implicated in ciliogenesis but repressed by GLI-1/2 mediated SHH activation. Here, we investigate the genomic landscape of BSS tumors and the functional interactions between CYLD and CENPV.
SKINTEGRITY.CH Principal Investigators are underlined:
- Chiticariu E, Regamey A, Huber M, Hohl D. (2020). CENPV Is a CYLD-Interacting Molecule Regulating Ciliary Acetylated α-Tubulin. J Invest Dermatol 140, 66.
- Bal E, Park HS, Belaid-Choucair Z, Kayserili H, Naville M, Madrange M, Chiticariu E, Hadj-Rabia S, Cagnard N, Kuonen F, Bachmann D, Huber M, Le Gall C, Côté F, Hanein S, Rosti RÖ, Aslanger AD, Waisfisz Q, Bodemer C, Hermine O, Morice-Picard F, Labeille B, Caux F, Mazereeuw-Hautier J, Philip N, Levy N, Taieb A, Avril MF, Headon DJ, Gyapay G, Magnaldo T, Fraitag S, Crollius HR, Vabres P, Hohl D, Munnich A, Smahi A. (2017). Mutations in ACTRT1 and its enhancer RNA elements lead to aberrant activation of Hedgehog signaling in inherited and sporadic basal cell carcinomas. Nat Med 23, 1226