Genodermatoses

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Genodermatoses

Genodermatoses are genetically transmitted skin disorders. The team’s objective is to understand the potential offered by human pluripotent stem cells (keratinocytes, melanocytes, fibroblasts) to develop therapeutic applications for Genodermatoses.

Using protocols for differentiating human pluripotent stem cells of embryonic origin (hES ) or induced pluripotency (hiPS) into specialized skin cells, the team is developing two main lines of research:

Pathological modeling

The objective of this axis is to generate modelsin vitro of pathologies of genetic origin, by differentiating iPS carrying a mutation in a gene coding for a particular protein involved in a disease. The team works on several pathologies, such as Epidermolysis Bullosa or vitiligo. These models are then characterized phenotypically and functionally to identify a pathological phenotype. They can then be used to understand the mechanisms of the pathology, or as a screening model for pharmaceutical molecules.

Cell therapy :

Here, the objective is to develop cellular therapies for skin repair. The team is particularly focused on the development of a product composed of keratinocytes derived from pluripotent stem cells to treat chronic leg ulcers, particularly in the context of sickle cell ulcers (PACE program). In a second phase, this work paved the way for the complexification of the product by including other iPS-derived cell types, such as fibroblasts, in order to improve the healing efficiency (Genesis Program).

In parallel, in order to improve yields and control production costs of cell therapy products, a program is being developed to establish a continuous, non-destructive and standardized quality control of the differentiation of these cells using holographic microscopy and deep learning. (Stellar Program).

Team members

Christine BALDESCHI

Team Leader & University Professor (UEVE)

Christine joined I-Stem in 2007 as a professor at the University of Evry. At I-Stem, she is developing cell therapy and pathological modeling approaches for the treatment of skin disorders associated with genetic diseases, using pluripotent stem cell derivatives.

Nathalie Holic

Assistant Professor (UEVE)

Nathalie is a lecturer at the University of Evry and joined I-Stem in 2017. Thanks to her expertise in genome engineering, she is developing innovative molecular tools to create cellular models to characterize epidermolysis bullosa simplex.

Manoubia SAIDANI

Engineer (CECS)

Manoubia joined the Genodermatoses team at I-Stem in 2008, and is involved in the development of skin cell models derived from pluripotent stem cells. These 2D and 3D models enable her to model skin pathologies such as epidermolysis bullosa and vitiligo.

Sophie DOMINGUES

Engineer (CECS)

Sophie has been working at I-Stem since 2011, as part of the Genodermatoses team’s PACE cell therapy project. This project aims to develop reconstructed skin in the laboratory that can be used as a biological dressing to treat skin ulcers linked to a genetic disease.

Annabelle DARLE

Engineer (CECS)

Annabelle joined the Genodermatoses team in 2015. She works on the PACE and STELLAR cell therapy projects. She is also interested in the mechanisms of stem cell differentiation into keratinocytes using molecular biology techniques.

Jennifer ALLOUCHE

Post-Doc (UEVE)

After a thesis completed at I-Stem in 2015 on the potential of pluripotent stem cells to model pigmentary diseases and a postdoctorate at Harvard on melanogenesis, Jennifer returned to I-Stem in 2020. Her research focuses on the development of new therapeutic strategies for vitiligo. In the Genodermatosis team, she has been responsible for pathological modeling of pigment disorders since 2023.

Tatiana SAOUDI

Engineer (CECS)

A member of the team since January 2021, Tatiana works on the Genesis project, in particular on the differentiation of human induced pluripotent stem cells into fibroblasts and their associated quality controls.

Céline BOURE

Engineer (CECS)

A member of the team since February 2021, Céline works on the Genesis project. She is contributing to the development of cell differentiation processes and associated quality controls for cells and the final product, for the manufacture of artificial skin.

Marion CHALOT

Engineer (CECS)

Joining the team in 2022 after completing her PhD at the CEA, Marion is an associate researcher and head of the Genesis project in the Genodermatoses team. She is working on the creation of artificial skin for grafting using tissue engineering.

Sabrina MARTINEAU

PhD Student

Having joined the Genodermatose team in 2019 as a Master 1 intern, Sabrina went on to complete her Master 2 internship and began a PhD in October 2020. Her thesis project involves studying the molecular mechanisms of Epidermolysis Bullosa Simple using a keratinocyte model derived from human pluripotent stem cells.

Bénédicte DE MUYLDER

Research technician

Assistant Inserm Engineer, joining I-Stem in September 2023. Bénédicte participates in the various cell therapy and modeling projects of the Genodermatoses team.

Patricia Senet

Clinical Dermatology Doctor

Patricia is a dermatologist at Tenon Hospital (Assistance Publique – Hôpitaux de Paris). She joined I-Stem in 2023 on a part-time clinical research position at APHP for 2 years. She will be in charge of developing the clinical phases of the PACE project (chronic leg wounds of genetic origin).

Collaborations

Christine Bodemer, Smail Hadj-Rabia, Nathalia Bellon
Department of Dermatology, Reference Centre for Genodermatoses and Rare Skin Disease (MAGEC), Hopital Universitaire Necker-Enfants Malades, APHP, Paris, France.

Epidermolyse bulleuse Program

Iprasense, Geoffrey Esteban
5 Avenue de l'Europe Hélioparc, 1er étage, 34830 Clapiers

Stellar Program (BPI funding)

Plateforme d’Innovation en BioThérapies (PIBT) – EFS, Clémentine Gamonet
Etablissement Français du Sang – Bourgogne Franche Comté 8 Rue du Dr Jean François Xavier GIROD 25020 BESANCON CEDEX

Stellar Program (BPI funding)

Patricia Senet, PH
Hopital Tenon, Service de Dermatologie, Allergologie, Médecine Vasculaire, AP-HP Sorbonne Université Hopital TENON, 4 rue de la Chine 75970 PARIS Cedex 20

PACE Program

Jean-Jacques Lataillade, Marina Trouillas, Institut de Recherche Biomédicale des Armées (IRBA) Unité de Thérapie Cellulaire et Tissulaire (U.TCT) Antenne Centre de Transfusion Sanguine des Armées
1 rue du Lieutenant Raoul BATANY BP 410 92141 CLAMART cedex

PACE Program

Karine Tertrais, Sophie Derenne, EFS Atlantic Bio GMP
2 rue Aronnax 44800 Saint Herblain

GENESIS Consortium

Guillaume OLIVE, Mathilde GIRARD, URGO / ADHARA
42, rue de longvic – BP 157 – 21304 Chenôve Cedex

GENESIS Consortium

Katja SCHUERER, DASSAULT SYSTEM
10 Rue Marcel Dassault, 78140 Vélizy-Villacoublay

GENESIS Consortium

Dominique SIGAUDO-ROUSSEL, Laboratoire de Biologie tissulaire et Ingénierie Thérapeutique
UMR 53057 Pass. du Vercors, 69007 Lyon

GENESIS Consortium

David Fisher MD, PhD
Chief of Dermatology Service, Massachusetts General Hospital

Vitiligo Program

Publications

Generation of heterozygous and homozygous NF1 lines from human-induced pluripotent stem cells using CRISPR/Cas9 to investigate bone defects associated with neurofibromatosis type 1.

01 January 2024

Darle Annabelle,

Mahiet Thibault,

Aubin Déborah,

Doyen Manon,

El Kassar Lina,

Parfait Béatrice,

Lemaitre Gilles,

Baldeschi Christine,

Allouche Jennifer,

Holic Nathalie,

Frontiers in cell and developmental biology

Generating Functional and Highly Proliferative Melanocytes Derived from Human Pluripotent Stem Cells: A Promising Tool for Biotherapeutic Approaches to Treat Skin Pigmentation Disorders.

29 March 2023

Saidani Manoubia,

Darle Annabelle,

Jarrige Margot,

Polveche Hélène,

El Kassar Lina,

Julié Séverine,

Bessou-Touya Sandrine,

Holic Nathalie,

Lemaitre Gilles,

Martinat Cécile,

Baldeschi Christine,

Allouche Jennifer,

International journal of molecular sciences

Human-Induced Pluripotent Stem Cell‒Derived Keratinocytes, a Useful Model to Identify and Explore the Pathological Phenotype of Epidermolysis Bullosa Simplex.

01 October 2022

Coutier Julien,

Bonnette Manon,

Martineau Sabrina,

Mercadier Aurélie,

Domingues Sophie,

Saidani Manoubia,

Jarrige Margot,

Polveche Hélène,

Darle Annabelle,

Holic Nathalie,

Hadj-Rabia Smail,

Bodemer Christine,

Lemaitre Gilles,

Martinat Cécile,

Baldeschi Christine,

The Journal of investigative dermatology

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