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    Cutaneous biology

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    Team leader

     

    The "Cutaneous Biology" team combines fundamental and translational approaches in order to understand skin homeostasis better and three severe associated skin diseases as well: wound healing delay, carcinogenesis and adnexal inflammation (hidrosadenitis suppurativa and acne). To carry out our work, we are using new animal models such as the naked-mole rat as well as human samples.

     

     Objectives

    1/ Delayed skin healing and fetal stem cells:

    We focused our work on the ability of fetal cells (transferred from the fetus to the mother’s bone marrow during pregnancy) to facilitate delayed maternal healing. We have discovered that Ccl2 electively triggers the mobilization of peculiar fetal stem cells. Our goals are first to further explore the therapeutic potential of Ccl2 further in maternal wound healing, then perform a comprehensive profiling of signaling pathways that recruit fetal cells and last investigate the heterogeneity and the hierarchy of these cells.

    2/ Skin carcinogenesis:

    Congenital Melanocytic Nevi (CMN) are tumors that present a risk of malignant transformation into melanoma. Recently we have found that a sole post-zygotic NRAS mutation was sufficient to trigger CMN pathogenesis and that clonogenic melanocytic cell subpopulations maintained these lesions when cooperating with keratinocytes. Our aims are to target specific signaling pathways below NRAS in pre-clinical models of CMN and investigate the role of keratinocyte-melanocyte interactions in the development of CMN. We have also built an analysis of melanoma dissemination and of non UV induced skin cancers in order to depict their pathways.

    3/ Adnexal inflammation:

    We are investigating the relationships between pathogenic bacteria and skin and characterized two P. acnes surface proteins: CAMP1 and DsA1, a fibrinogen-binding protein. Now our goals are to determine the role of DsA1 and CAMP1 during the inflammatory process and further characterize the structure and properties of DsA1.We have also developed a project on the study of sebaceous stem cells in a severe follicular disorder, namely hidrosadenitis suppurativa (HS).

     

     

     

    Main Publications

    • Local Inhibition of MEK/Akt Prevents Cellular Growth in Human Congenital Melanocytic Nevi. Rouillé T*, Aractingi S*, Kadlub N, Fraitag S, How-Kit A, Daunay A, Hivelin M, Moguelet P, Picard A, Fontaine RH*, Guégan S*. J Invest Dermatol. 2019 Sep;139(9):2004-2015.
    • Cutaneous wound healing in diabetic mice is improved by topical mineralocorticoid receptor blockade.Nguyen VT, Farman N, Palacios-Ramirez R, Sbeih M, Behar-Cohen F, Aractingi S*, Jaisser F*.J Invest Dermatol. 2019 Jul 3. pii: S0022-202X(19)31849-4.
    • Characterization of a Propionibacterium acnes Surface Protein as a Fibrinogen-Binding Protein. Grange PA, Raingeaud J, Morelle W, Marcelin AG, Calvez V, Dupin N.  Sci Rep. 2017 Jul 25;7(1):6428.
    • Ccl2/Ccr2 signalling recruits a distinct fetal microchimeric population that rescues delayed maternal wound healing. Castela M, Nassar D, Sbeih M, Jachiet M, Wang Z, Aractingi S. Nat Commun. 2017 May 18;8:15463.
    • Delayed Healing of Sickle Cell Ulcers Is due to Impaired Angiogenesis and CXCL12 Secretion in Skin Wounds. Nguyen VT, Nassar D, Batteux F, Raymond K, Tharaux PL, Aractingi S. J Invest Dermatol. 2016 Feb;136(2):497-506.

     

    Fundings

    In 2019 the Skin Biology team obtained an ANR funding for the analysis of fetal stem cells implicated in wound healing and is part of a RHU (Success) for the study of a new device using fetal cell secretome to treat child burns. In 2017, we also obtained a Leo Foundation and a Société Française de Dermatologie fundings which is helping us in the analysis of the signaling pathways in carcinomas. Recently, R. Fontaine obtained an IDEX Emergence for his project on aging skin in the naked mole rat model. Bénédicte Oulès successfully became Chef de Clinique/Inserm/Fondation Bettencourt which will allow us to get financial support for her work on hidrosadenitis suppurativa.

     

    Patents

    • BRE-2016-1: Dupin N, Grange P, Calvez V, Marcelin AG. Meclozide derivatives and diclazuril derivatives for use in the prevention and/or the treatment of disorders associated to the inflammation induced by P acnes, August 2016: EP-16305912
    • BRE-2016-2: Dupin N, Grange P, Calvez V, Marcelin AG. Hycantone derivatives and primaquine derivatives for use in the prevention and/or the treatment of disorders associated with gammaherpesvirus, July 2016: EP16305782
    • BRE 2016-3: Farman N, Jaisser F, Nguyen VT, Behar Cohen, Aractingi S. Inhibiting mineralocorticoid receptor enhances wound healing. Pharmaceutical compositions for preventing glucocorticoid induced corneal or skin thinning EP, 2016: EPA 13305851
    • BRE 2016-4: Aractingi S, Castela M, Wang Zhe, Nassar D, Methods and pharmaceutical  compositions for the treatment of tissue lesions, 2016: EP16305512.2
    • BRE-2015-1: Dupin N, Grange P, Calvez V, Marcelin AG, Raingeaud J. Isolated peptides and fragments thereof from fibrinogen for use as drugs, particularly in skin inflammatory diseases, March 2015: EP15305414, extension PCT 2016