RECHERCHE AXES
The research carried out by the LGRK on human skin focuses on three areas:
1 – Molecular determinants of the 'stem cell' character or 'stemness'.
This upstream research axis focuses on knowledge of the fundamental characteristics of the epithelial stem cells and progenitors present within the interfollicular epidermis and the hair follicle. Points of interest include the search for phenotypic criteria associated with the 'stem cell' character, as well as the deciphering of the regulatory networks of the 'immaturity versus differentiation' balance. The TGFB1 pathway and associated transcription factors are particularly studied for their involvement in the control of stemness. More generally, this research integrates the conventional coding genome (genes coding the proteome), and the epigenome (genes producing non-coding transcripts), in particular the class of long non-coding RNAs (lncRNAs).
2 – Cultured skin substitutes.
This translational axis aims to provide concepts and innovations for the benefit of the field of cutaneous cell and tissue therapies. A first line of work concerns the development of effectors promoting a pro-stemness action, thus allowing a more effective preservation of epidermal stem cells ex vivo, in the context of bioengineering architectures of skin substitutes. The targeted gain concerns the quality of regeneration. A second line of work concerns the problem of immune rejection, which restricts the fields of use of allogeneic grafts. The approach explored consists of vectorizing molecules that promote a tolerogenic signal in skin cells, with a view to generating grafts with attenuated immunogenicity.
On this axis, and within the framework of the 'Priority Research Programs and Equipment' (PEPR) 'Biotherapies - Bioproduction', the LGRK is the coordinator of a targeted program on skin cell and tissue therapies: acronym 'Bioengineered Skin France'.
3 – Cutaneous radio-pathologies.
This axis focuses on the cutaneous consequences of genotoxic stresses induced by ionizing radiation (IR), in particular exposure of healthy skin in the context of medical applications (imaging, radiotherapy). A first aspect studied is the impact of this medical exposome on the integrity and functions of epidermal stem cells and progenitors. One aspect of interest concerns dermal fibroblasts, studied for their status as primary effector cells in the development of radiation-induced skin fibrosis. The molecular effectors of physiopathology are studied at the level of the coding genome and the non-coding transcriptome. Candidate targets for the design of corrective approaches are sought.