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.

KEYWORDS
epidermis, genetic syndromes, keratinocytes, skin tumor syndromes

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.

 

Prof. Em. Daniel Hohl
Lausanne University Hospital (CHUV)
Department of Dermatology
Avenue de Beaumont 29
1011 Lausanne

Email   Website