In addition to its staff, the unit welcomes 3 persons in emeritus.
Research unit CITHEFOR
Cibles thérapeutiques, formulation et expertise préclinique du médicament
Bâtiment AB, Campus Brabois-Santé
9 Avenue de la Forêt de Haye, BP 20199
54505 VANDOEUVRE-LES-NANCY
FRANCE
Ariane BOUDIER
ariane.boudier [at] univ-lorraine.fr
Nathalie DEGOUSEE
nathalie.degousee [at] univ-lorraine.fr
The UR CITHEFOR develops new therapeutic strategies for vascular diseases (treatment of stroke, prevention of atherosclerosis and restenosis). Its strategy is based on the sustained and controlled release (physiological concentration) of nitrogen monoxide (NO), to optimize its beneficial protective effects at the vascular level.
CITHEFOR thus synthesizes and ensures quality control, according to regulatory standards, of NO donors of the S-nitrosothiols (RSNO) type, physiological or derived from innovative compounds. These molecules have a known degree of purity and pharmaceutical quality. The control of NO release is optimized, depending on the route of administration, using particulate formulations (nano or micro) or nanostructured materials.
The pharmacological effects, including the identification of new targets as well as the modulation of redox signaling pathways, induced by free or formulated NO donors are evaluated using models (enzymatic, cellular, tissue and animal).
CITHEFOR is interested in the modulation of the regulatory pathways of vascular function through S-nitrosation of proteins (addition of NO to a thiol function) in connection with redox signaling.
Our expertise makes it possible to establish and study the connections between the antioxidant properties of redox molecules and the NO-dependent signaling pathways.
Supervising body(ies)
Key numbers of the unit
- 15 Lecturers and professor
- - Staff scientists
- 8 Qualified research supervisors (HDR)
- 5Technical and administrative staff
- 9phD students
- 103 Publications ACL
2015-2020
Research topics / Know-how
Innovative molecules and nanoformulations from nitric oxide donors
The unit is a single multidisciplinary team and is articulated in a single project around the following disciplines: pharmacology, cell biology, galenic pharmacy, physicochemistry and analytical chemistry.
This project addresses two major scientific questions to position nitric oxide (NO) donors of the S-nitrosothiol (RSNO) type in vascular pathologies: the control of NO release and the understanding of the induced signaling. These questions are intimately interconnected since to understand the molecular, cellular and tissue mechanisms involved, it is necessary to obtain a prolonged and controlled release of NO (in the nanomolar range). This can only be achieved by using original formulations.
This project is part of the drug development process in coherence with the teaching affiliation at the Faculty of Pharmacy of all the teachers-researchers of the unit.
Contact(s) :
Ariane BOUDIERariane.boudier [at] univ-lorraine.fr
Staff
Ariane BOUDIER Director UL
Igor CLAROT Co Director UL
Nathalie DEGOUSEE Administrative Manager UL
phD students
Pas de soutenance pour le moment
- CELINE DELAITRECaractérisation pharmacologique et fonctionnelle de ligands traceurs du récepteur AT1 de l'angiotensine II pour l'étude de nouvelles approches thérapeutiquesPharmacological and functional characterization of angiotensin II AT1 receptor tracer ligands for the study of new therapeutic approachesDirecteur de thèse :François DUPUISCo-directeur de thèse :Sandra LECAT
- CELIA BOUKOUFICaractérisation des propriétés catalytiques de nanoparticules d'or immobiliséesCharacterization of the catalytic properties of immobilized gold nanoparticlesDirecteur de thèse :Igor CLAROTCo-directeur de thèse :Ariane BOUDIER
- MARGAUX BERTHOUMONITORING DE S-NITROSOTHIOLS DANS DES MATRICES BIOLOGIQUES GRACE A DES SONDES NANOSTRUCTUREESS-NITROSOTHIOLS MONITORING IN BIOLOGICAL MATRICES BY NANOSTRUCTURATED PROBES.Directeur de thèse :Igor CLAROTCo-directeur de thèse :Arnaud PALOTTA
- JUSTINE BONETTIPotentiel thérapeutique des S-nitrosothiols dans la prévention de l’athérosclérose : Modulation de la métaplasie des monocytes et cellules musculaires lisses en cellules spumeusesTherapeutic potential of S-nitrosothiols in the prevention of atherosclerosis: Modulation of monocytes and smooth muscle cells metaplasia into foam cellsDirecteur de thèse :Caroline GAUCHERCo-directeur de thèse :Alfonso POMPELLACo-tutelle :Università di SIENA
ITALIE - JORDAN BEURTONOptimisation physicochimique de films fonctionnalisés pour des applications cardio-vasculairesPhysicochemical optimization of functionalized films for cardiovascular applicationsDirecteur de thèse :Ariane BOUDIERCo-directeur de thèse :Philippe LAVALLE
- Romain SCHMITTS-nitrosoglutathion et perméabilité intestinale : de la mise en place d’un modèle de chambre de Ussing à l’étude de l’impact de ce donneur de monoxyde d’azote sur la barrière intestinaleS-nitrosoglutathione and intestinal permeability: from the implementation of a Ussing chamber model to the study of the impact from this nitric oxide donor on the intestinal barrierDirecteur de thèse :Anne SAPIN-MINET
- Yi ZHOUMécanismes de franchissement de la barrière intestinale et de stockage vasculaire des S-nitrosothiols pour l'amélioration de formulations orales de NOMechanisms of S-nitrosothiols intestinal permeability and NO store formation within vascular wall to improve NO oral delivery systemsDirecteur de thèse :Caroline GAUCHERCo-directeur de thèse :Marianne PARENT
Equipment
The unit has many analytical, experimental and formulation tools that allow in particular:
- To develop innovative formulations,
- To characterize the formulations,
- To quantify the substances of interest in biological media,
- To evaluate their cellular toxicity,
- To observe a potential pharmacological effect.
- Stratagene MX3000P
- Trans-Blot Turbo
- Mini-PROTEAN 3 Electrode Assembly
- P/ACE MDQ
- UV-2600
- FP8300 + FMP825
Services
Histological platform
This platform allows the histological and morphometric study of tissues (paraffin, cryosections), cells (fixed or living) or polymer particles. The microscopic analyzes are carried out by optical microscopy with white light (conventional, phase contrast or polarized) or fluorescence.
Contact(s) :
Caroline SARRADOcaroline.sarrado [at] univ-lorraine.frPharmaceutical technology
This platform allows preparation and characterization of pharmaceutical dosage forms. Technics apply more particularly to biodegradable formulations such as nano-, microparticules and implants…
Contact(s) :
Anne SAPIN-MINETanne.sapin [at] univ-lorraine.frPhysicochemistry platform
The physico-chemistry platform offers spectrophotometric (UV-Vis, fluorescence) and separation (HPLC and capillary electrophoresis) analytical tools necessary for the development of analytical and bioanalytical methods for the evaluation of drug candidates and innovative formulations (nano and micro- particulates).
Contact(s) :
Igor CLAROTigor.clarot [at] univ-lorraine.frPreclinical expertise
Preclinical expertise (telemetry, isolated organs: arteries, intestines, etc.) is outsourced to the Animal Center Campus Brabois-Santé: pharmacodynamics, mechanisms of action, pharmacokinetics, identification of therapeutic targets (nitrosation of proteins, including receptors for angiotensin II).
Contact(s) :
François DUPUISfrancois.dupuis [at] univ-lorraine.frCell biology platform
The cell / molecular biology platform offers models of stress (oxidant, ferroptosis), inflammation, wound healing and intestinal barrier for the evaluation of the mechanism of action (redox biomarkers, gene expression, protein identification) of drug candidates and their formulations.
Contact(s) :
Caroline GAUCHERcaroline.gaucher [at] univ-lorraine.fr
Innovations
- - Patents
- 2 Invention declarations
- - ERC grant
Publications
- - Nitric Oxide: Biology and Chemistry - 10.1016/j.niox.2020.08.001Yi Zhou, Caroline Gaucher, Isabelle Fries, Mehmet-Akif Hobekkaya, Charlène Martin, Clément Leonard, Frantz Deschamps, Anne Sapin-Minet, Marianne Parent
- - Biochemical Pharmacology - 10.1016/j.bcp.2019.113686Caroline Perrin-Sarrado, Yi Zhou, Valérie Salgues, Marianne Parent, Philippe Giummelly, Isabelle Lartaud, Caroline Gaucher
- - International Journal of Pharmaceutics - 10.1016/j.ijpharm.2019.118583Arnaud Pallotta, Ariane Boudier, Benjamin Creusot, Emilie Brun, Cécile Sicard-Roselli, Rana Bazzi, Stéphane Roux, Igor Clarot
- - British Journal of Pharmacology - 10.1111/bph.14644Marie‐lynda Bouressam, Sandra Lecat, Alexandre Raoul, Caroline Gaucher, Caroline Perrin-Sarrado, Isabelle Lartaud, François Dupuis
- - Biochemical Pharmacology - 10.1016/j.bcp.2018.06.018Justine Bonetti, Yi Zhou, Marianne Parent, Igor Clarot, Haiyan Yu , Isabelle Fries-Raeth, Pierre Leroy, Isabelle Lartaud, Caroline Gaucher
- - Talanta - 10.1016/j.talanta.2017.11.016Arnaud Pallotta, Valentin Philippe, Ariane Boudier, Pierre Leroy, Igor Clarot
- - Nitric Oxide: Biology and Chemistry - 10.1016/j.niox.2017.10.004Marie-Lynda Bouressam, Benjamin Meyer, Ariane Boudier, Igor Clarot, Pierre Leroy, Alessandro Genoni, Manuel Ruiz-Lopez, Philippe Giummelly, Patrick Liminana, Valérie Salgues, Mostafa Kouach, Caroline Perrin-Sarrado, Isabelle Lartaud, François Dupuis
- - Nitric Oxide: Biology and Chemistry - 10.1016/j.niox.2017.07.004Eugénia Belcastro, Wen Wu, Isabelle Fries-Raeth, Alessandro Corti, Alfonso Pompella, Pierre Leroy, Isabelle Lartaud, Caroline Gaucher
- - Nanomedicine: Nanotechnology, Biology and Medicine - 10.1016/j.nano.2016.05.006Wen Wu, Caroline Perrin-Sarrado, Hui Ming, Isabelle Lartaud, Philippe Maincent, Xian-Ming Hu, Anne Sapin-Minet, Caroline Gaucher
- - Drug Delivery - 10.3109/10717544.2015.1122676Shefaat Ullah Shah, Marie Socha, Isabelle Fries, Stéphane Gibaud