Group Huber

Marcel Huber

Dr. Marcel Huber


The rising worldwide incidence of skin cancer is mainly due to increased UV levels caused by ozone layer depletion, to higher voluntary sun exposure and to the increase in life expectancy. Knowledge of molecular mechanisms responsible for the development of skin tumours permits more efficient treatment options. Loss of the control on the switch between proliferation and differentiation is a hallmark of tumour growth. TRAIP (TRAF-interacting protein) is required for cell proliferation in primary keratinocyte and melanocytes, the two major cell types of the skin giving rise to more than 90% of all skin cancers. The expression of TRAIP is increased in basal cell carcinomas, the most common skin cancer. TRAIP belongs to a group of enzymes, called E3 ubiquitin ligases, which are involved in the regulation of protein metabolism. We have several projects investigating the role of TRAIP in proliferation of normal and cancer cells using cell biology methods and genetically modified mice.

Major Scientific Contributions

1) Identification of gene mutations causing genetically inherited skin diseases. This work identifies important proteins that are required for the formation of the epidermal barrier and tissue homeostasis. Molecular methods and animal models are used to study in-depth the epidermis-specific functions of structural proteins and enzymes.

  • Rothnagel J., Dominey A., Dempsey L., Longley M., Greenhalgh D., Gagne T., Huber M., Hohl D., Frenk E., & Roop D. Mutations in the rod domain of keratin 1 and 10 in epidermolytic hyperkeratosis. Science 257, 1128-1130 (1992).
  • Rothnagel J. A., Traupe H., Wojcik S., Huber M., Hohl D., Pittelkow M. R., Saeki H., Ishibashi Y., & Roop D. R. Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Siemens. Nat Genet 7, 485-490 (1994).
  • Huber M., Rettler I., Bernasconi K., Frenk E., Lavrijsen S. P. M., Ponec M., Bon A., Lautenschlager S., Schorderet D. F., & Hohl D. Mutations of keratinocyte transglutaminase in lamellar ichthyosis. Science 267, 525-528 (1995).

Smith F.J.D., Corden, L.D., Rugg E.L., Ratnavel R., Leigh I.M., Moss C., Tidman M.J., Hohl D., Huber M., Kunkeler L., Munro C.S., Lane E.B., & McLean W.H.I. Missense mutations in keratin 17 cause either Pachyonychia congenita type 2 or a phenotype resembling steatocystoma multiplex. J Invest Dermatol 108, 220-223 (1997).

  • Huber M., Yee V.C., Burri N., Vikerfors E., Lavrijsen A.P.M., Paller A.S., & Hohl D. Consequences of seven novel mutations on the expression and structure of keratinocyte transglutaminase. J Biol Chem 272, 21018-21026 (1997).
  • Koch P., de Viragh P.A., Schärer E., Bundman D., Longley M. A., Bickenbach J., Kawachi Y., Suga Y., Zhou Z., Huber M., Hohl D., Kartasova T., Jarnik M., Steven A. C., & Roop D. R. Lessons from loricrin-deficient mice: Compensatory mechanisms maintaining skin barrier in the absence of a major cornified envelope protein. J Cell Biol 151, 389-400 (2000).
  • Macari F., Landau M., Cousin P., Baruk M., Brenner S., Panizzon R.G., Schorderet D., Hohl D., & Huber M. Mutation in the connexin 30.3 gene in a family with erythrokeratodermia variabilis. Am J Hum Genet 67, 1296-1301 (2000).
  • Fischer J., Bouadjar B., Heilig R., Huber M., Lefévre C., Jobard F., Macari F., Bakija-Konsuo A., Ait-Belkacem F., Weissenbach J., Lathrop M., Hohl D., & Prud’homme J.-F. Mutations in the gene encoding SLURP-1 in Mal de Meleda. Hum Mol Genet 10, 875-880 (2001).
  • Huber M., Floeth M., Borradori L., Schäcke H., Rugg E.L., Lane E.B., Frenk E., Hohl D., & Bruckner-Tuderman L. A large in frame deletion in the cytoplasmatic domain of BP180/collagen XVII causes a phenotype with predominant features of epidermolysis bullosa simplex. J. Invest. Dermatol. 118, 185-192 (2002).
  • Huber M., Siegenthaler G., Mirancea N., Marenholz I., Nizetic D., Breitkreutz D., Mischke D., & Hohl D. Isolation and characterization of human repetin, a member of the fused gene family of the epidermal differentiation complex. J Invest Dermatol 124, 998-1007 (2005).
  • Contzler R., Favre B., Huber M., & Hohl D. Cornulin, a new member of the fused gene family, is expressed during epidermal differentiation. J Invest Dermatol 124, 990-997 (2005).
  • *Müller F.B., *Huber M., *Kinaciyan T., Hausser I., Schaffrath C., Krieg T., Hohl D., Korge B.P., & Arin M. A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis. Hum Mol Genet 15, 1133-1141 (2006). *The first three authors contributed equally to this work.
  • Wen Y., Liu Y., Xu Y., Zhao Y., Hua R., Wang K., Sun M., Li Y., Yang S., Zhang XJ., Kruse R., Cichon S., Betz R.C., Nöthen M.M., van Steensel M.A., van Geel M., Steijlen P.M., Hohl D., Huber M., Dunnill G.S., Kennedy C., Messenger A., Munro C.S., Terrinoni A., Hovnanian A., Bodemer C., de Prost Y., Paller A.S., Irvine A.D., Sinclair R., Green J., Shang D., Liu Q., Luo Y., Jiang L., Chen H.D., Lo W.H., McLean W.H., He C.D., & Zhang X. Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis. Nat Genet 41, 228-233 (2009).

2) Identification and functional analysis of proteins that are involved in skin carcinogenesis. Furthermore, animal models are generated to examine the role of anti-oxidative molecules and growth factors in the formation of skin cancer.

  • Bignell GR., Warren W., Seal S., Takahashi M., Rapley E., Barfoot R., Green H., Brown C., Biggs P. J., Lakhani S. R., Jones C., Hansen J., Blair E., Hofmann B., Siebert R., Turner G., Evans D.G., Schrander-Stumpel C., Beemer F. A., van Den Ouweland A., Halley D., Delpech B., Cleveland MG., Leigh I., Leisti J., Rasmussen S., Wallace M. R., Fenske C., Banerjee P., Oiso N., Chaggar R., Merrett S., Leonard N., Huber M., Hohl D., Chapman P., Burn J., Swift S., Smith A., Ashworth A., & Stratton M. R. Identification of the familial cylindromatosis tumour-suppressor gene. Nat Genet 25, 160-165 (2000).
  • Regamey A., Hohl D., Liu J.W., Roger T., Kogerman P., Toftgård R., & Huber M. The tumor suppressor CYLD interacts with TRIP and regulates negatively nuclear factor B activation by tumor necrosis factor. J Exp Med 198, 1959-1964 (2003).
  • Auf dem Keller U., Huber M., Beyer T., Bugnon P., Braun S., Rülicke T., Johnson J.A., Hohl D., & Werner S. Nrf transcription factors are crucial for skin tumor prevention but not for wound healing. Mol Cell Biol 26, 3773-3784 (2006).
  • Almeida S., Maillard C., Itin P., Hohl D., & Huber M. Five new CYLD mutations in skin appendage tumors and evidence that aspartic acid 681 in CYLD is essential for deubiquitinase activity. J Invest Dermatol 128, 587-593 (2008).
  • MalanchiI., PeinadoH., KassenD., HussenetT., MetzgerD., ChambonP., Huber M., HohlD., CanoA., BirchmeierW., & Huelsken J. Cutaneous cancer stem cell maintenance is dependent on â-catenin signaling. Nature 452, 650-653 (2008).
  • Almeida S., Ryser S., Obarzanek-Fojt M., Hohl D., & Huber M. The TRAF-interacting protein (TRIP) is a regulator of keratinocyte proliferation. J Invest Dermatol 131, 349-357 (2011).
  • Antsiferova M., Huber M.*, Meyer M.*, Piwko-Czuchra A.*, Ramadan T., MacLeod A.S., Havran W.L, Dummer R., Hohl D., & Werner S. Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response. Nat. Commun. 2:576 doi: 10.1038/ncomms1585 (2011). *These authors contributed equally to this work.
  • Chapard, C.; Hohl, D.; & Huber, M. The role of the TRAF-interacting protein (TRAIP) in proliferation and differentiation. Exp Dermatol 21, 321-326 (2012).


Christophe Chapard, PhD student
Tobias Gleich, PhD student
Anita Mariotto, PhD student
Daniel Bachmann, lab technician


The biological function of TRAIP in the epidermis
Swiss National Science Foundation, 10/2011 – 09/2014
Identification of substrates of the E3 ubiquitin ligase TRAIP
Emma Muschamp Foundation 1/2012-1/2015


Contact Info:
Service de dermatologie et vénéréologie
Av. de Beaumont 29
1011 Lausanne CHUV, Switzerland
 Dernière mise à jour le 28/09/2020 à 15:15