Christophe GUIGNABERT
  • E-mail :[email]
  • Phone : +33 1 40 94 88 33
  • Location : Le Plessis-Robinson, France
Last update 2020-07-30 22:06:37.664

Christophe GUIGNABERT PhD Cardiovascular Research

Course and current status

Dr. Christophe GUIGNABERT joined Inserm in 2009 and is now Research Director (DR2; Professor) at UMR_S 999 (a mixed Inserm-Université Paris-Saclay unit) located in Le Kremlin-Bicêtre, FRANCE.

Since 2010, he is leading a research team entitled « Endothelial dysfunction & Therapeutic innovation in PAH » in the UMR_S 999 headed by Pr. Marc Humbert: http://www.u999.universite-paris-saclay.fr/en/team-1/pah-physiology-topics.html

-Since 2017: Professor (Director of Research (DR2) INSERM, Ph.D) - UMR_S 999 - INSERM - Université Paris-Saclay Pr. Marc Humbert's lab

-2012-2017:  Associate Professor (Chargé de Recherche (CR1) INSERM, Ph.D) - UMR_S 999 - INSERM - Université Paris-Saclay Pr. Marc Humbert's lab

-2012: Accreditation to conduct research (HDR)                                                      

-2010-2012:  Assistant Professor (Chargé de Recherche (CR2) INSERM) - UMR_S 999 - INSERM - Université Paris-Saclay Pr. Marc Humbert's lab

-2008-2010:  Post-Doct #3 (Universite Paris-Sud - Le Kremlin Bicêtre, France) -  UMR_S 999 - INSERM - Université Paris-Saclay Pr. Marc Humbert's lab

-2006-2008:  Post-Doct #2 (STANFORD University, CA, USA) - Stanford University School of Medicine - Pr. Marlene Rabinovitch's lab

-2004-2006:  Post-Doct #1 (Univ. Paris-Est Créteil - Val de Marne, France) - INSERM UMR_S 651 - Univ. Paris-Est Créteil - Pr. Serge Adnot's Lab

-2001-2005:  Ph.D "Epithelial alveolar repair & MECs & MMPs" - Univ. Paris-Est Créteil - Val de Marne, France - Pr. Marie-Pia d'Ortho's lab

Scientific summary

My primary research for the past several years seeks to: (1) Provide a better understanding of the role played by pulmoanry endothelial cells (ECs) in the vascular PH remodeling; (2) Investigate abnormalities in EC communications with other vascular cells (smooth muscle cells, myofibroblasts and pericytes) and immune cells (Treg); (3) Restore the expression/protein activity identified in vitro on isolated cells and in vivo through experimental models of pulmonary hypertension. 

My Team has already been able to highlight several events reflecting major functional alterations in the pulmonary vascular endothelium, including among others: 1) a transition from a quiescent state (without adhesion capacity) to an activated state with adhesive capacity; 2) an aberrant hyper-proliferative and apoptosis resistant phenotype; 3) a pro-inflammatory phenotype characterized by an excessive release of various key cytokines and chemokines: interleukin (IL)-1α, IL-6, IL-8, IL-12, CCL2/monocyte chemotactic protein (MCP)-1; 4) an excessive production and secretion of various key growth factors including fibroblast growth factor-2 (FGF-2; basic FGF), angiotensin-II (Ang II), and macrophage migration inhibitory factor (MIF). 

In addition to the contributions described above, we have also reported for the first time increased pericyte coverage of pulmonary arteries in experimental and human PAH, an abnormality that is a potential source of smooth muscle–like cells involved in the pulmonary vascular remodeling. We obtained evidence that dysfunctional endothelium from idiopathic PAH patients, through an aberrant release of key mediators contribute to this vascular abnormality.

Furthermore, using three different approaches of suppressing BMP9 action in rodents, we also provided evidence that the selective loss/inhibition of BMP9 in mice does not predispose to PH.

Finally, we have also demonstrated that dasatinib induces endothelial cell dysfunction via increased production of reactive oxygen species (ROS), a phenomenon that can partly explain dasatinib-related pleural effusion as well as the increase susceptibility to PH development.

 

Scientific Focus: Pulmonary hypertension (PH) – Pulmonary vascular remodeling – Endothelial dysfunction – Endothelial communications – Pericyte – Endothelial cell – Growth factors – Animal models.

Website: http://www.u999.universite-paris-saclay.fr/en/team-1/pah-physiology-topics.html

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