RNA, RNP Structure-Function-Maturation (RNA-RNP)

Team RNA, RNP Structure-Function-Maturation (RNA-RNP) studies the machinery which assembles ribonucleoprotein particles, notably through structure-function approaches, as well as the mechanisms of RNA processing.

The team also investigates the mechanisms of action of post-transcriptional (epitranscriptomic) RNA-modifying enzymes and the functions of small and long non-coding RNAs and RNA-protein complexes, under both normal and pathological conditions (including cancer, heart failure and arthritis). In these situations, RNAs are evaluated both for their contribution to physiopathology and as potential biomarkers.

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Molecular, Cellular, Therapeutic Engineering & Glycosyltransferases (MolCelTEG)

Team Molecular, Cellular, Therapeutic Engineering & Glycosyltransferases (MolCelTEG) investigates the assembly mechanisms of glycosaminoglycans (GAG) and collagens, the main macromolecules of extracellular matrices and key players in the transduction of extracellular signals. A new axis investigates the function of nuclear GAG mediating epigenetic mechanisms and genome organization.

This team implements a multi-scale strategy that combines cellular, molecular and "omics" approaches to the development of animal model to elucidate the structure, functions and regulations of enzymes responsible for the biosynthesis and maturation of GAG (in particular glycosyltransferases) and of collagen. The findings of team 2 have a broad clinical significance in the context of connective tissue disorders, in particular rare genetic diseases, cancers, fibrosis and osteoarthritis, thereby lying the molecular and biochemical ground for the development of diagnostic and therapeutic strategies against these diseases. These studies are located at the interfaces between glycobiology, biochemistry, biophysics, chemistry and pathophysiology.

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Molecular & Structural Enzymology (MSE)

Team Molecular & Structural Enzymology (MSE) aims to elucidate the molecular mechanisms underlying cellular regulation and signaling mediated by hydrogen peroxide (H2O2) and hydrogen sulfide (H2S), which specificity depends on the complex chemistry of sulfur (thiolate, disulfide, persulfide, sulfenic and sulfinic acids, or thiosulfinate), critical to various physiopathological processes. The team draws on its strong, recognized expertise in enzymology, along with competences in biophysics, mass spectrometry and redox cellular biochemistry.

The team is also interested establishing structure-function relationships for a family of modular enzymes, the polyketide synthases (PKSs), which produce molecules of pharmacological interest including antibiotics, immunosuppressants and anti-cancer agents. The objective is to apply these insights to the productive engineering of modular PKSs using synthetic biology, towards the generation of high-value polyketide derivatives.

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Inflammation, Phenotypic Deregulation & Pathological Joint Remodeling (IDePRAP)

Team Inflammation, Phenotypic Deregulation & Pathological Joint Remodeling (IDePRAP) combines molecular approaches and animal experimentation to develop new strategies to control joint inflammation via modulation of the PPARgamma et RORgammat nuclear receptors. It also carries out translational research on the involvement of these factors in joint manifestations associated with chronic digestive inflammation (IBD).

The team is also interested in the molecular mechanisms underlying the modification of joint cell phenotype (chondrocytes, subchondral osteoblasts) during the development of osteoarthritis, and the processes of pathological mineralization. This approach includes studying the role of key factors of mineralization (Pi/PPi balance, Matrix Gla proteins), and the development of strategies to control the Wnt ("Wingless Integration site") pathway using peptides, thereby correcting the imbalance between the canonical and noncanonical pathways.

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Bioengineering, Regenerative Medicine & Tissue Characterisation (BioReMaTCh)

Team Bioengineering, Regenerative Medicine & Tissue Characterisation (BioReMaTCh) develops regenerative medicine strategies by (1) vectorization of MSCs or active principles for the treatment of osteoarthritis lesions, (2) by construction of vascular grafts from human umbilical cord, and (3) by tissue bioengineering by controlling the behaviour (adhesion, proliferation, migration, differentiation) of MSCs (medullary, synovial, adipose and umbilical), within biomaterials to produce vascular and joint substitutes. These multilayered and/or three-dimensional biomaterials (3D printing) “functionalized” with the progenitor cells and / or their secretion products are then tested in animal models of cartilage deficiency or by arterial bypass surgery.

On the osteoarticular side and thanks to a collaboration with the PTIBC imaging platform and with the imaging services of the CHRU, the team is developing multi-scale imaging using second harmonic macroscopy and stimulated Raman microscopy (SRM) to validate osteocartilaginous biomaterials prior to implantation, as well MRI to monitor biomaterials implanted in animals, having previously labelled the progenitor cells with paramagnetic tracers (nanoparticles). In collaboration with rheumatology service of the CHRU, the team also evaluates the diagnostic performance of CT and MRI scans in osteoarticular pathologies. On the vascular side and thanks to the collaboration with the cardiovascular service of the CHRU, the follow-up by echo-doppler and angiography verifies the permeability as well as the qualities of the vascular graft implanted in the animal.

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Cellular Engineering, Cellular Immunotherapy and Translational Approaches (CECITA)

Team Cellular Engineering, Cellular Immunotherapy and Translational Approaches (CECITA) develops, in preclinical models and with a translational approach, new cellular immunotherapy strategies to modulate the immune response or for anti-infectious or anti-cancer therapies.

Mesenchymal stem cells, invariant NKT lymphocytes (iNKT) and myeloid suppressive cells (MDSC) are explored in modulating the immune response during sepsis, the graft versus host reaction after allogeneic hematopoietic stem cell transplantation or the autoimmune lupus. Virus-specific T lymphocytes (CTL) (adenovirus, BK virus or SARS-CoV-2) are studied for anti-infectious purposes.

In cancers, NK cells are studied in medulloblastoma, and some lymphocytes (CTL or iNKT), genetically modified to express a chimeric antigen receptor (CAR), are developed in leukemias. This work benefits from close links with the Cell and Tissue Therapy Unit (UTCT) of the Nancy CHRU, which makes it possible to produce therapeutic cells at clinical grade (good manufacturing practices) and the implementation of clinical trials.

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