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Introduction team

Founded by Pr. Françoise Morel in 1991, the main research theme of the GREPI team, GROUPE DE RECHERCHE ET D'ÉTUDE DU PROCESSUS INFLAMMATOIRE (GREPI/AGIM CNRS FRE 3405), concern the study of the role of innate immunity in inflammation and in particular the impact in this process of reactive oxygen derivatives produced by NADPH oxidases (Phox-Nox Group).

The structure/function studies carried out in GREPI, concerning the catalytic subunit of phagocyte NADPH oxidase, Nox2 (or gp91phox), the prototype of Nox, have led to a molecular understanding of Chronic Septic Granulomatosis (CGD), a disease associated with the absence of phagocyte NADPH oxidase activity.
These questions contribute to the understanding of cellular stress at the origin of human pathologies.

GREPI is also at the origin of the creation of the "Club oxydase" in 1999, a club gathering all the French-speaking teams working on Nox, which meets every 2 years.
The team develops its projects in close proximity to practitioners and patients, the University Clinic of Rheumatology of Grenoble University Hospital, the ortho-geriatric center and the geriatric clinic, among others. This situation offers the opportunity to combine quality clinical research and opens the possibility of having well-identified pathological samples.

Scientific theme and general objectives

The main research theme of GREPI for many years has been oriented towards inflammation mediated by the production of reactive oxygen derivatives with

1. the activating, functional and structural mechanisms of NADPH oxidases (NOX)

2. the initiation of the contact and complement phase in the inflammatory tissues (endothelium).

3. the identification and study of biomarkers in chronic pathologies.

These questions contribute to the understanding of cellular stress at the origin of human pathologies.

The team develops its projects in the proximity of practitioners and patients. This location offers the opportunity to investigate on appropriate human models and opens the possibility to have well-identified pathological samples.

 

Research topics
Kinin activation and catabolism: entities for angioedema
Kinins are released locally from their parental molecules, the kininogens, as a result of limited proteolysis by Serine proteases called kallikreins

Complement in adaptive immunity
Complement is firmly established as instructor of adaptive immunity and is required for germinal centre formation, Ab responses and normal B cell memory development. We provided an illustration demonstrating that a C3-/- patient exhibits a memory B cell defect, with impaired vaccine Ab production

NADPH oxidases (Nox)
ROS became a very important goal and a very dynamic research field. This interest relates to the recognized roles of ROS as critical mediators in variety of physiological functions and processes e.g. host defence, inflammation, hormone biosynthesis, cell proliferation, migration and differentiation, gene expression and signal transduction.

Rheumatoid diseases
  • Osteoarthritis: Several evidence support the involvement of kinins in the pathophysiology of OA: (1) kinin B2R have been detected in synovial tissue of OA patients
  • Rheumatoid Arthritis (RA): Together with the basic research on Nox2 activation, we investigate the impact of ROS produced by neutrophil Nox2 on inflammatory disorders, especially in the RA, one of the most common autoimmune diseases
  • Spondyloarthritis: Spondyloarthritis (SpA) pathogenesis involves environmental factors such as infections (C. trachomatis in reactive arthritis)
  • Rett syndrome: Rett syndrome (RTT) is a severe X-linked autism spectrum disorder caused by a dysfunction of a transcriptional factor methyl-CpG binding protein 2 (MeCP2) that strikes randomly one to 10,000 girls in their early childhood when males instead died in utero

Transfusion and transplantation
This issue is entering in the field of the GREPI know-how with the inflammatory parameters developed during the transfusion adverse reactions. It will take advantage of the expertise of neutrophil, endothelial cells, complement and kinins. A program dedicated to TRALI etiopathogenesis has been launched (2012), a starting point of investigation interests of GREPI in transfusion.

 

Team members
Presentation of team members (introductory sentence)

GREPI team is co-directed by  Athan BAILLET and Bertrand HUARD.

Team coordinator(s)

Permanent members

Others members

PhD students


Associate collaborators

  • mvcnguyen [at] chu-grenoble.fr (Dr. Nguyen Chuong), Sinnovial CTO (start-up)

Contact

Address: Site Santé - Faculté de médecine de Grenoble, bâtiment Jean Roget (8e étage), 38706 La Tronche