Modeling Xeroderma Pigmentosum Group C (XPC) Using Human Pluripotent Stem Cells to Study the Mechanisms Underlying Impaired Skin Homeostasis

Location: iSTEM (CECS), Genopole Campus, Corbeil-Essonnes, France
Duration: 6 months (Master's Year 2 Internship)
Research Team: Genodermatoses Team
This research project will be carried out at iSTEM (Institute for Stem Cell Therapy and
Exploration of Monogenic Diseases), a research institute located within Genopole in
Corbeil-Essonnes, France. The institute develops human disease models using
pluripotent stem cells (embryoic stem cells, ES, and induced pluripotent stem cells,
iPSCs) to better understand disease mechanisms and develop innovative therapeutic
approaches

This research project will be carried out at iSTEM (Institute for Stem Cell Therapy and Exploration of Monogenic Diseases), a research institute located within Genopole in Corbeil-Essonnes, France. The institute develops human disease models using pluripotent stem cells (embryoic stem cells, ES, and induced pluripotent stem cells, iPSCs) to better understand disease mechanisms and develop innovative therapeutic approaches.

Project Description

Xeroderma Pigmentosum Group C (XPC) is a rare genetic disorder caused by mutations in the XPC gene, which plays a critical role in DNA damage repair through the nucleotide excision repair (NER) pathway. Although the disease is primarily known for its extreme sensitivity to ultraviolet (UV) radiation and the highly increased risk of skin cancer, accumulating evidence also suggests a progressive impairment of skin homeostasis, associated with premature skin aging and reduced regenerative capacity. However, the cellular and molecular mechanisms underlying these alterations particularly the potential involvement of extracellular matrix remodeling and disrupted interactions between skin compartments remain largely unknown.

The objective of this Master's research project is to identify the cellular and molecular mechanisms through which XPC deficiency disrupts the maintenance of skin homeostasis. To achieve this, the project will utilize human induced pluripotent stem cells (iPSCs) together with isogenic XPC knockout (XPC-KO) cell lines. The iPSCs will be differentiated into various skin cell types to generate human models of Xeroderma Pigmentosum in both two-dimensional (2D) cultures and three-dimensional (3D)
reconstructed skin models, recapitulating the key pathological features observed in patients. More specifically, the project aims to determine how XPC deficiency affects the functions of skin cells, assess whether it leads to alterations in extracellular matrix remodeling, and characterize the consequences of these changes on interactions between the dermal and epidermal compartments. This work will contribute to a better understanding of the role of XPC in maintaining skin homeostasis and may facilitate the identification of novel therapeutic targets for Xeroderma Pigmentosum.

Key Skills and Techniques to Be Acquired

Working within the specialized research environment at iSTEM,

the student will acquire a broad range of multidisciplinary skills, including:
Advanced cell culture: Maintenance, expansion, and manipulation of human induced pluripotent stem cells (iPSCs) and their skin-derived derivatives.
Stem cell differentiation: Differentiation of iPSCs into relevant skin cell types.
3D tissue engineering: Generation of biomimetic 3D skin models incorporating various skin cells to investigate extracellular matrix remodeling dynamics.
Molecular phenotyping: Performing RT-qPCR, Western blotting, immunohistochemistry (IHC), and targeted proteomic analyses.
High-resolution imaging: Using advanced microscopy techniques to visualize and analyze structural morphometry of the 3D reconstructed skin models.

Candidate Profile / Requirements

We are looking for a highly motivated, curious, and rigorous Master's (M2) student with the following qualifications:
Academic background: Enrolled in a Master's program in Cell Biology, Biomedical Sciences, Stem Cell Biology, Bioengineering, or a closely related discipline.
Technical skills: Previous hands-on experience in mammalian cell culture is highly desirable. Familiarity with basic molecular biology techniques (eg, qPCR and protein-based assays) is considered an advantage.
Personal qualities: Strong organizational and communication skills, ability to work effectively as part of a team, good command of English, and a genuine interest in contributing to therapeutic research for rare diseases.

Academic background: Enrolled in a Master's program in Cell Biology, Biomedical
Sciences, Stem Cell Biology, Bioengineering, or a closely related discipline.
Technical skills: Previous hands-on experience in mammalian cell culture is highly
desirable. Familiarity with basic molecular biology techniques (eg, qPCR and protein-
based assays) is considered an advantage.
Personal qualities: Strong organizational and communication skills, ability to work
effectively as part of a team, good command of English, and a genuine interest in
contributing to therapeutic research for rare diseases.
Application Procedure
Interested candidates should send their application directly to: Dr. Jennifer Allouche
(jallouche@istem.fr) and Dr. Ali Nasrallah (anasrallah@istem.fr).
The application package must include:
* A scientific CV
* A cover letter
* Academic transcripts from the first year of the Master's program (M1) and the first
semester of the second year (M2)
* The email address of one academic or professional referee