Dr. Hohl trained at the University of Zurich and its Dermatology Clinics from 1985-1990 when he also spent a three years sabbatical at NCI, NIH in Bethesda, Maryland and the Baylor College, Houston. Dr. Hohl works since 1990 at CHUV and UNIL in Lausanne, was called « primo et unico loco » as professor to the DKFZ in 1995, was invited professor at ETHZ from 2000 to 2005 and went for a sabbatical to Paris at the Hôpitaux Necker and St. Louis in Paris in 2013. Dr. Hohl has served in diverse international societies, and was President of both the MD-PhD Commission UNIL and EPFL and the European Society of Pediatric Dermatology. Recipient of diverse awards, Dr. Hohl is also Honorary Member of the French and Serbian Societies of Dermatology.
Genetic skin diseases reveal the importance and function of the affected genes/proteins in skin homeostasis. Their study allows the identification of cellular, biochemical and molecular mechanisms indispensable for the complex differentiation leading to the formation of the cutaneous barrier, protecting the body from the environment and preventing water loss. Most of genodermatoses, except vulgar ichthyosis, are rare, rendering the access of biological material from affected patients and their analysis very difficult. The parallel development of in vitro human and mouse models circumvents this problem and facilitate the investigation of the biological pathways affected by a mutated gene/protein. However, these models need to validate by comparing them with real clinical samples before they can be used to assess novel therapeutic approaches so hardly needed.
The skin is the outer body envelope providing a barrier against environmental, chemical, physical, or microbial hazards. This complex organ is composed of the epidermis, the underlying dermis containing vascular, neural and adnexal structures and the hypodermis. Skin appendages include hair follicles with sebaceous glands, apocrine and eccrine glands, but in organogenesis also nails and the mammary gland. The epidermis is a multilayered tissue formed by terminal differentiation of keratinocytes moving through spinous, granular layers and cornified layer, and contains melanocytes, Langerhans, and Merkel cells. Epithelial progenitor cells in the bulge area of the hair follicle or the basal epidermal layer give rise to epidermis as well as to skin appendages. Major signaling mechanisms for correct development of the epidermis and the adnexal structures have recently been unraveled.
Excessive UVB and UVA exposure and chronic injury are the driving forces in the formation of sporadic skin cancers. Genetic factors are involved in familial predisposition to skin cancer formation. The major types of skin cancer are basal cell carcinoma (BCC, 80%), squamous cell carcinoma (SCC, 16%) and malignant melanoma (4%) which represent 99% of skin tumors in the United States . The lifetime risk to develop these malignancies is around to 1:3 in Switzerland. Their mortality is relatively low but morbidity is high.
FNS Grant 310030-173102 and Placid Nicod Foundation:
“The role of ARP-T1 in Skin and BCC”
BCC is the most common malignant tumor in humans. In Switzerland, life time risk for suffering from a skin BCC is one out of three. Although mortality due to non-melanoma skin cancer is relatively low, its morbidity is high and is accompanied by heavy personal burden and enormous, rising costs for the society with a growing elderly population. Identification of the key molecular events is critical to implement novel strategies of treatment and prevention of these tumors.
ARP-T1 dysfunction causes the ectodermal dysplasia and tumor syndrome BDCS. ACTRT1 appears to be a tumor suppressor gene, and thus is a novel actor implicated in the pathogenesis of BCC. We are particularly interested in how dysfunction by mutation expressed either in quiescent follicular stem cells or during epidermal differentiation alters cellular signaling and ultimately induces proliferation. Understanding of the molecular pathways and mechanisms involved is essential for the development of novel therapeutic approaches not only for BDCS and BCC, but cancer in general.
More precisely, we propose that ARP-T1 acts as a novel tumor suppressor and as of yet unidentified (direct or indirect) actor in SHH signaling. We hypothesize that 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. Beyond BDCS, our studies will further detail our understanding of centrosome and primary cilia formation, processes involved in numerous pathologies including diverse types of developmental defects and cancer eg. medulloblastoma, osteosarcoma or breast cancer and the growing group of hereditary ciliopathies. Above all, this project will shed light on the basic mechanism of primary cilia formation and function, and how they are controlled in carcinogenesis.
Dind Cottier Foundation:
From Cylindroma to Basal Cell Cancer: the CYLD-CENPV axis
The Spiegler-Brooke syndrome (SBS) is characterized by multiple hair follicle tumors and caused by mutations in the CYLD gene, a deubiquitinase that regulates a large number of signaling pathways. KO or KI mouse models do not phenocopy spontaneously the human disease but develop only papillomas after chemical carcinogenesis. Therefore, the pathological mechanism of such hair follicle tumor formation and more generally the role of CYLD in carcinogenesis remains an open question. 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 not only involved in the spindle assembly checkpoint but also in DNA damage response. Another, CENPV, is a nuclear and microtubule binding protein localized at centromeres that affects the localization of the passenger complex proteins Aurora B and INCENP, and sugoshin-1. Further, cylindromas are ciliated, CENPV is found in cilia, CYLD is implicated in ciliogenesis and repressed by GLI-1/2 mediated SHH activation. Here, we propose to investigate the genomic landscape of BSS tumors and the functional interactions between CYLD and CENPV in epidermal homeostasis and particularly its role in the SHH pathway.
Meylan P, Lang C, Mermoud S, Johannsen A, Norrenberg S, Hohl D, Vial Y, Prod'hom G, Greub G, Kypriotou M, Christen-Zaech S
J Invest Dermatol. 2017 Dec;137(12):2497-2504
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,
Nat Med. 2017 Oct;23(10):1226-1233
Feldmeyer L, Mylonas A, Demaria O, Mennella A, Yawalkar N, Laffitte E, Hohl D, Gilliet M, Conrad C
JAMA Dermatol. 2017 Apr 1;153(4):304-308
Marquardt L, Lacour M, Hoernes M, Opitz L, Lecca R, Volkmer B, Reichenbach J, Hohl D, Ansari M, Ozsahin H, Gungor T, Pachlopnik Schmid J.
J Eur Acad Dermatol Venereol. 2017 Mar;31(3):e147-e8.
Antsiferova M, Piwko-Czuchra A, Cangkrama M, Wietecha M, Sahin D, Birkner K, Amann VC, Levesque M, Hohl D, Dummer R, Werner S
EMBO Mol Med. 2017 Jan;9(1):27-45
Feldmeyer L, Szeverényi I, Mandallaz M, Lane EB, Hohl D
Case Rep Dermatol. 2016 Sep-Dec;8(3):344-349
Pavlova O, Fraitag S, Hohl D
J Invest Dermatol. 2016 Dec;136(12):2453-2461
Karpate A, Barcena C, Hohl D, Bisig B, de Leval L
Virchows Arch. 2016 Nov;469(5):591-596
Kuonen F, Aschwanden J, Dimaio DJ, Elston DM, Gilliet M, Hohl D, Gaide O
Eur J Dermatol. 2016 Oct 1;26(5):465-469
Zhang L, Ferreyros M, Feng W, Hupe M, Crumrine DA, Chen J, Elias PM, Holleran WM, Niswander L, Hohl D, Williams T, Torchia EC, Roop DR
PLoS One. 2016;11(8):e0161465
Degueurce G, D'Errico I, Pich C, Ibberson M, Schütz F, Montagner A, Sgandurra M, Mury L, Jafari P, Boda A, Meunier J, Rezzonico R, Brembilla NC, Hohl D, Kolios A, Hofbauer G, Xenarios I, Michalik L
EMBO Mol Med. 2016 Aug;8(8):919-36
D'Erme AM, Hohl D
Dermatol Ther. 2016 Jul;29(4):286-7
Mariotto A, Pavlova O, Park HS, Huber M, Hohl D
J Invest Dermatol. 2016 May;136(5):905-11
Fellmann F, Angelini F, Wassenberg J, Perreau M, Arenas Ramirez N, Simon G, Boyman O, Demaria O, Christen-Zaech S, Hohl D, Belfiore M, von Scheven-Gete A, Gilliet M, Bochud PY, Perrin Y, Beck Popovic M, Bart PA, Beckmann JS, Martinet D, Hofer M
J Allergy Clin Immunol. 2016 Apr;137(4):1189-1196.e2
Di Domizio J, Pagnoni A, Huber M, Hohl D, Gilliet M
Rev Med Suisse. 2016 Mar 30;12(512):660-4
Gleich T, Chiticariu E, Huber M, Hohl D
Exp Dermatol. 2016 Feb;25(2):85-91
Hohl D, Borradori L, Leclerc-Mercier S. In: Saurat JH, Lipsker D, Thomas L, Borradori L, Lachapelle J, editors.
6e ed. Paris: Elsevier Masson; 2016. p. 326-35.
Hohl D. In: Saurat JH, Lipsker D, Thomas L, Borradori L, Lachapelle J, editors.
6e ed. Paris: Elsevier Masson; 2016. p. 336-45.
Leuenberger M, Berner J, Di Lucca J, Fischer L, Kaparos N, Conrad C, Hohl D, So A, Gilliet M
Dermatology. 2016;232(2):254-8
Rolfs F, Huber M, Kuehne A, Kramer S, Haertel E, Muzumdar S, Wagner J, Tanner Y, Böhm F, Smola S, Zamboni N, Levesque MP, Dummer R, Beer HD, Hohl D, Werner S, Schäfer M
Cancer Res. 2015 Nov 15;75(22):4817-29
Chapard C, Hohl D, Huber M
Oncotarget. 2015 Aug 28;6(25):20933-45
Czernielewski J, Hohl D
Rev Med Suisse. 2015 Apr 1;11(468):763-4, 766-7
Chapard C, Meraldi P, Gleich T, Bachmann D, Hohl D, Huber M
J Cell Sci. 2014 Dec 15;127(Pt 24):5149-56
Ryser S, Schuppli M, Gauthier B, Hernandez DR, Roye O, Hohl D, German B, Holzwarth JA, Moodycliffe AM
J Invest Dermatol. 2014 Jan;134(1):192-202
Montagner A, Delgado MB, Tallichet-Blanc C, Chan JS, Sng MK, Mottaz H, Degueurce G, Lippi Y, Moret C, Baruchet M, Antsiferova M, Werner S, Hohl D, Saati TA, Farmer PJ, Tan NS, Michalik L, Wahli W
EMBO Mol Med. 2014 Jan;6(1):80-98
Antsiferova M, Martin C, Huber M, Feyerabend TB, Förster A, Hartmann K, Rodewald HR, Hohl D, Werner S
J Immunol. 2013 Dec 15;191(12):6147-55
Kypriotou M, Rivero D, Haller S, Mariotto A, Huber M, Acha-Orbea H, Werner S, Hohl D
Front Immunol. 2013;4:246
Kypriotou M, Boéchat C, Huber M, Hohl D
PLoS One. 2013;8(7):e67869
Spring P, Vernez M, Maniu CM, Hohl D
Dermatol Online J. 2013 Jun 15;19(6):18572
Rolfs F, Huber M, Gruber F, Böhm F, Pfister HJ, Bochkov VN, Tschachler E, Dummer R, Hohl D, Schäfer M, Werner S
Cancer Res. 2013 Jun 1;73(11):3460-9
Spring P, Fellmann F, Giraud S, Clayton H, Hohl D
Am J Dermatopathol. 2013 Apr;35(2):241-5
Rausch T, Cairoli A, Benhattar J, Spring P, Hohl D, de Leval L
APMIS. 2013 Jan;121(1):79-84
Hohl D, Huber M
Hautarzt. 2013 Jan;64(1):12-21
Kypriotou M, Huber M, Hohl D
Exp Dermatol. 2012 Sep;21(9):643-9
Schäfer M, Farwanah H, Willrodt AH, Huebner AJ, Sandhoff K, Roop D, Hohl D, Bloch W, Werner S
EMBO Mol Med. 2012 May;4(5):364-79
Chapard C, Hohl D, Huber M
Exp Dermatol. 2012 May;21(5):321-6
Chollet A, Hohl D, Perrier P
Rev Med Suisse. 2012 Apr 4;8(335):743-6
Kasper M, Jaks V, Hohl D, Toftgård R
J Clin Invest. 2012 Feb;122(2):455-63
Antsiferova M, Huber M, Meyer M, Piwko-Czuchra A, Ramadan T, MacLeod AS, Havran WL, Dummer R, Hohl D, Werner S
Nat Commun. 2011 Dec 6;2:576
Obarzanek-Fojt M, Favre B, Kypriotou M, Ryser S, Huber M, Hohl D
Eur J Cell Biol. 2011 Apr;90(4):279-90
Almeida S, Ryser S, Obarzanek-Fojt M, Hohl D, Huber M
J Invest Dermatol. 2011 Feb;131(2):349-57
Oji V, Tadini G, Akiyama M, Blanchet Bardon C, Bodemer C, Bourrat E, Coudiere P, DiGiovanna JJ, Elias P, Fischer J, Fleckman P, Gina M, Harper J, Hashimoto T, Hausser I, Hennies HC, Hohl D, Hovnanian A, Ishida-Yamamoto A, Jacyk WK, Leachman S, Leigh I, Ma
J Am Acad Dermatol. 2010 Oct;63(4):607-41
Dumortier A, Durham AD, Di Piazza M, Vauclair S, Koch U, Ferrand G, Ferrero I, Demehri S, Song LL, Farr AG, Leonard WJ, Kopan R, Miele L, Hohl D, Finke D, Radtke F
PLoS One. 2010 Feb 18;5(2):e9258
Hohl D
Rev Med Suisse. 2010 Jan 13;6(231):15-7
Lurati MC, Hohl D
Arch Dermatol. 2009 Dec;145(12):1447-52
Koegel H, von Tobel L, Schäfer M, Alberti S, Kremmer E, Mauch C, Hohl D, Wang XJ, Beer HD, Bloch W, Nordheim A, Werner S
J Clin Invest. 2009 Apr;119(4):899-910
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 RC, Nöthen MM, van Steensel MA, van Geel M, Steijlen PM, Hohl D, Huber M, Dunnill GS, Kennedy C, Messenger A, Munro CS, Terrinoni A, Hovnanian A, Bodemer C,
Nat Genet. 2009 Feb;41(2):228-33
Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P, Huber M, Hohl D, Cano A, Birchmeier W, Huelsken J
Nature. 2008 Apr 3;452(7187):650-3
Almeida S, Maillard C, Itin P, Hohl D, Huber M
J Invest Dermatol. 2008 Mar;128(3):587-93
Feldmeyer L, Keller M, Niklaus G, Hohl D, Werner S, Beer HD
Curr Biol. 2007 Jul 3;17(13):1140-5
Lefort K, Mandinova A, Ostano P, Kolev V, Calpini V, Kolfschoten I, Devgan V, Lieb J, Raffoul W, Hohl D, Neel V, Garlick J, Chiorino G, Dotto GP
Genes Dev. 2007 Mar 1;21(5):562-77
Favre B, Plantard L, Aeschbach L, Brakch N, Christen-Zaech S, de Viragh PA, Sergeant A, Huber M, Hohl D
J Invest Dermatol. 2007 Feb;127(2):301-8
Contzler R, Regamey A, Favre B, Roger T, Hohl D, Huber M
Biochem Biophys Res Commun. 2006 Nov 10;350(1):208-13
auf dem Keller U, Huber M, Beyer TA, Kümin A, Siemes C, Braun S, Bugnon P, Mitropoulos V, Johnson DA, Johnson JA, Hohl D, Werner S
Mol Cell Biol. 2006 May;26(10):3773-84
Müller FB, Huber M, Kinaciyan T, Hausser I, Schaffrath C, Krieg T, Hohl D, Korge BP, Arin MJ
Hum Mol Genet. 2006 Apr 1;15(7):1133-41
Hohl D
Exp Dermatol. 2005 Oct;14(10):777-80
Miksch S, Lumsden A, Guenther UP, Foernzler D, Christen-Zäch S, Daugherty C, Ramesar RK, Lebwohl M, Hohl D, Neldner KH, Lindpaintner K, Richards RI, Struk B
Hum Mutat. 2005 Sep;26(3):235-48
Huber M, Siegenthaler G, Mirancea N, Marenholz I, Nizetic D, Breitkreutz D, Mischke D, Hohl D
J Invest Dermatol. 2005 May;124(5):998-1007
Contzler R, Favre B, Huber M, Hohl D
J Invest Dermatol. 2005 May;124(5):990-7
Yang T, Liang D, Koch PJ, Hohl D, Kheradmand F, Overbeek PA
Genes Dev. 2004 Oct 1;18(19):2354-8
Lehr E, Hohl D, Huber M, Brown D
J Med Virol. 2004 Mar;72(3):478-83
Fontao L, Tasanen K, Huber M, Hohl D, Koster J, Bruckner-Tuderman L, Sonnenberg A, Borradori L
J Invest Dermatol. 2004 Jan;122(1):65-72
Regamey A, Hohl D, Liu JW, Roger T, Kogerman P, Toftgard R, Huber M
J Exp Med. 2003 Dec 15;198(12):1959-64
Plantard L, Huber M, Macari F, Meda P, Hohl D
Hum Mol Genet. 2003 Dec 15;12(24):3287-94
Chimienti F, Hogg RC, Plantard L, Lehmann C, Brakch N, Fischer J, Huber M, Bertrand D, Hohl D
Hum Mol Genet. 2003 Nov 15;12(22):3017-24
Bitoun E, Micheloni A, Lamant L, Bonnart C, Tartaglia-Polcini A, Cobbold C, Al Saati T, Mariotti F, Mazereeuw-Hautier J, Boralevi F, Hohl D, Harper J, Bodemer C, D'Alessio M, Hovnanian A
Hum Mol Genet. 2003 Oct 1;12(19):2417-30
Marrakchi S, Audebert S, Bouadjar B, Has C, Lefèvre C, Munro C, Cure S, Jobard F, Morlot S, Hohl D, Prud'homme JF, Zahaf A, Turki H, Fischer J
J Invest Dermatol. 2003 Mar;120(3):351-5
Landau M, Cohen-Bar-Dayan M, Hohl D, Ophir J, Wolf CR, Gat A, Mevorah B
Pediatr Dermatol. 2002 Jul-Aug;19(4):285-92
Beer HD, Munding C, Dubois N, Mamie C, Hohl D, Werner S
J Biol Chem. 2002 Jun 7;277(23):20740-9
Rodondi N, Darioli R, Ramelet AA, Hohl D, Lenain V, Perdrix J, Wietlisbach V, Riesen WF, Walther T, Medinger L, Nicod P, Desvergne B, Mooser V
Ann Intern Med. 2002 Apr 16;136(8):582-9
Huber M, Floeth M, Borradori L, Schäcke H, Rugg EL, Lane EB, Frenk E, Hohl D, Bruckner-Tuderman L
J Invest Dermatol. 2002 Jan;118(1):185-92
Bakija-Konsuo A, Basta-Juzbasic A, Rudan I, Situm M, Nardelli-Kovacic M, Levanat S, Fischer J, Hohl D, Loncaric D, Seiwert S, Campbell H
Dermatology. 2002;205(1):32-9
Schorderet DF, Huber M, Laurini RN, Von Moos G, Gianadda B, Délèze G, Hohl D
Prenat Diagn. 1997 May;17(5):483-6
Hohl D
Dermatology. 1997;195(1):86-8