CV Science

Christophe GUIGNABERT PhD Cardiovascular Research

Course and current status

Christophe GUIGNABERT (PhD, ATSF, FERS) joined Inserm in 2009 and is now Director of Research (DR2; Full Professor of Molecular Biology & Physiology) at UMR_S 999 (a mixed Inserm-Université Paris-Saclay research unit) located in the Paris-Saclay School of Medicine, Le Kremlin-Bicêtre, FRANCE.

Since 2010, he is the Director of the Research Team « Endothelial dysfunction & Therapeutic innovation in PAH »: http://www.u999.universite-paris-saclay.fr/en/team-1/pah-physiology-topics.html

-Since 2017: Full Professor of Molecular Biology & Physiology (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 major research interest focuses on the molecular and cellular mechanisms behind the process of vascular remodeling in Pulmonary Hypertension in order to identify and validate new therapeutic targets. In particular, my research is focused on how dysfunction in the BMP/TGF-β superfamily modulates the phenotypic heterogeneity of the pulmonary endothelium and on how pulmonary endothelial cells interact with their microenvironment.

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 pro-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; 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, we have also reported for the first time increased pericyte coverage of pulmonary arteries in experimental and human PH and provided evidence that the selective loss/inhibition of BMP9/BMPRII does not predispose experimental PH. Furthermore, we demonstrated that dasatinib induces EC dysfunction, a phenomenon that can partly explain dasatinib-related pleural effusion as well as the increase susceptibility to PAH development.

In different pre-clinical studies, we have already highlighted the therapeutical potentials of innovative drugs to limit pulmonary vascular remodeling that are in clinical development, such as pirfenidone, sacubitril/ valsartan, and antagonists that selectively target CXCL12 (Patent WO2018011376), TPH1, and MIF (Patent WO2015173433).

Recently, we have also identified 5 pronostic biomarkers for PAH that predict outcomes in PAH (Patent EP22306121 and Patent EP22306977) 

Scientific Production: Dr Guignabert authored more than 100 original research papers, 50 review articles, and more than 15 book chapters and has given numerous invited talks at national and international conferences. He has 4 patents in his name. He is an Associate Editor of the European Respiratory Journal and a member of multiple editorial boards and has mentored multiple MD and Ph.D scientists, of them many have productive and well-funded independent career.

Scientific Focus: Pulmonary hypertension (PH) – Vascular remodeling – Endothelial dysfunction – Cell microenvironment – Pericyte – Endothelial cell – BMP/TGF – Growth factors – Preclinical models.

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