Go to content Go to the menu Go to the search

PartnersSorbonne UniversitésUPMCInsermCNRS
Quick access, personalized services
Centre d'Immunologie et des Maladies Infectieuses
UPMC UMRS CR7 - Inserm U1135 - CNRS ERL 8255

Chemokines in pathologies and Inflammation - Christophe COMBADIERE

Team members

Team Research program

Inflammation is a hallmark of numerous human diseases and a key aspect of it is trafficking of immune cells into and out of the specific injured tissues. Thus, the challenge for the future will be to identify the trafficking molecules that will most specifically inhibit the key subsets of cells that drive disease processes without affecting the migration and function of leukocytes required for protective immunity.
Chemokines (CK) are typical immune and inflammatory mediators that not only allow a rapid and appropriate leukocyte migration to emergency signals but also control cellular responses. CK and their receptors (CKR) are central to the inflammatory process and are thus attractive targets for the pharmaceutical industry.
Our research program aims to establish the evidence that the CK-based therapy could become a new way of treatment of inflammatory diseases. It includes four approaches:

  1. structural and functional analysis of inflammatory CK and CKR,
  2. ex vivo studies that analyze the role of CK/CKR on subsets of leukocytes in human diseases,
  3. in vivo studies that characterize the role of CK/CKR in inflammatory mouse models,
  4. the development of CK/CKR-based therapeutic tools.


The project pipeline, from molecular analysis, proof-of-principle evaluation in murine models to valorization, is taking advantage of new short peptide-based antagonist candidates that have already shown strong efficacy in limiting monocyte infiltration in organs.

Technical expertise

  • Flow cytometry of adaptative and innate immune responses
  • Inflammatory murine models
  • GPCR signal transduction pathways (FRET, FRAPP, biosensors)
  • Cellular adhesion assays (static, flux, dual-pipettes)

Main achievements

  • Caracterisation of the role of the RCK in atherosclerosis, HIV infection, cancers, and neurodegenerative disorders.
  • Identification of genetic susceptibility markers for  atherosclerosis, HIV infection, cancers, and neurodegenerative disorders.
  • Development of CCR2 et CX3CR1 RCK antagonists
  • Evidence of oligomerization of CX3CR1 and of CX3CL1

External funding (current)

  • ANR (2013-2017) : Chemokpain
  • ANR (2015-2019) : CMOS
  • FRM (2016-2019) Sepsis - Team label

Publications (PDF):

(2017 - 2016 - 2015 - 2014 - 2013)

20/11/17

Traductions :

Contact

cimi-paris @ upmc.fr

To see

Key words

Immunology, Inflammation, monocyte, Chemokine, migration, adhesion, Signal transduction pathways

Fields of application

Infectious diseases, Inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, cancers