Innovative cell therapy strategies using next-generation CAR-T cell approaches in systemic sclerosis
Innovative cell therapy strategies using next-generation CAR-T cell approaches in systemic sclerosis
Description
Introduction:
The Laboratory of Immuno-Rheumatology at Institut Cochin seeks to recruit a post-doc with experience in immunology and bio-informatic. The successful candidate will join a highly multidisciplinary team, with experience spanning cell and molecular biology, and availability of numerous mice models related to fibro-inflammatory diseases. The lab projects are based on finding innovative biomarkers or therapeutic targets in immune-inflammatory diseases. All our projects ambition a high translation to patients taking advantage of our rheumatology units. Our lab is based in a multidisciplinary institute organized with highly efficient multiple core facilities. (https://institutcochin.fr/equipes/pathogenie-traitements-innovants-maladies-fibro-inflammatoires-chroniques).
We are seeking a post-doc to work on a research project related to appealing new targets in systemic sclerosis, an autoimmune orphan disease characterized by systemic fibrosis. We are committed to investigate new cell therapy using CAR T cell technology beyond CD19 CAR T cells (PMID: 37610259). Inhibitory compounds will have to be investigated in complementary mice models. From a mechanistic point of view, expression and regulation in human tissue and cells will have to be investigated. Bio-informatic skills are required for analyses of the therapeutic challenges and to explore potential new targets using in-house and public genetic data.
Project:
Previous experiments using CD19 CAR-T cells in fra2 transgenic mice model paradoxically resulted in exacerbated pulmonary fibrosis driven by secondary activation of lung-infiltrating CD4 T lymphocytes mimicking a cytokine release syndrome (PMID: 37610259). In contrast, polyclonal regulatory T cells (Treg) have previously demonstrated a significant protective effect in this model (PMID: 35255201). CAR-Treg represent an emerging therapeutic strategy combining CAR specificity with the immunoregulatory and pro-repair properties of Treg. We hypothesize that CD19 CAR-Treg may neutralize the deleterious effects observed with conventional CAR-T cells and restore a tissue microenvironment permissive for repair. We have in parallel another program on CAR-T targeting a fibrosis-specific protein that will be investigated using the same animal model.
Technical/methodological aspects:
The project involves animal models with multi-cell and tissue investigations with in particular the use of flow cytometry and molecular biology with single cell RNAseq.
Environment:
The institute provides state-of-the-art facilities. The lab is staffed with 4 principal investigators, 3 research assistants, 1 engineer, and 3 doctoral candidates studying the molecular and cellular aspects of fibro-inflammatory diseases. Cochin institut is located in the vibrant 14th arrondissement of Paris, close to the train stations Gare Montparnasse and Gare de Lyon.
Requirements
The successful candidate must have extensive experience in flow cytometry and molecular biology (RNA seq) mastering the required analytical software.
Postdoctoral fellows (max. 1-2 years post-PhD experience) are invited to apply. Contract will initially be for 1 year and can then be renewed.
Job ID: 84917981
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