CV Science

Christophe GUIGNABERT PhD Cardiovascular Research

Course and current status

Christophe GUIGNABERT (PhD, ATSF, FERS) joined Inserm in 2009 and has since been appointed as Director of Research (DR1) - Full Professor of Molecular Biology & Physiology - at UMR_S 999. This is a mixed Inserm-Université Paris-Saclay research unit located within the Paris-Saclay School of Medicine in 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 ( DR1) en 2023), Ph.D, ATSF, FERS) - 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

As a researcher, my primary focus is investigating the molecular and cellular mechanisms driving vascular remodeling in Pulmonary Hypertension. The ultimate goal of my work is to identify and validate potential therapeutic targets. Specifically, my research is aimed at understanding how dysfunction in the BMP/TGF-β superfamily contributes to the phenotypic heterogeneity of the pulmonary endothelium and how pulmonary endothelial cells interact with their microenvironment.

Through our research, my team has made significant progress in highlighting key functional alterations in the pulmonary vascular endothelium. For example, we have observed a transition from a quiescent state to an activated state with adhesive capacity, an aberrant pro-proliferative and apoptosis-resistant phenotype, and a pro-inflammatory phenotype characterized by excessive release of key cytokines and chemokines (such as interleukin (IL)-1α, IL-6, IL-8, IL-12, and CCL2). We have also observed an excessive production and secretion of various growth factors, including fibroblast growth factor-2 (FGF-2; basic FGF), angiotensin-II (Ang II), macrophage migration inhibitory factor (MIF), and activins. Our team was the first to report increased pericyte coverage of pulmonary arteries in both experimental and human PH, and we provided evidence that the selective loss/inhibition of BMP9/BMPRII does not predispose experimental PH. Additionally, our research shows that dasatinib can induce EC dysfunction, which partly explains dasatinib-related pleural effusion as well as the increased susceptibility to PAH development.

Our pre-clinical studies have identified several innovative drugs that show potential for limiting pulmonary vascular remodeling, including finerenone, pirfenidone, sacubitril/valsartan, and antagonists that selectively target CXCL12 (Patent WO2018011376), TPH1, and MIF (Patent WO2015173433). These drugs are currently in clinical development, and our research provides critical insights into their therapeutic potential.

Finally, our team has recently identified five prognostic biomarkers for PAH that can predict patient outcomes (Patent EP22306121 and Patent EP22306977): CXCL9, TRAIL, beta-NGF, activin A, and FSTL3. This breakthrough will have significant implications for the diagnosis and treatment of PAH, and we are excited to further validate these biomarkers in future studies.

Scientific Production: Dr. Guignabert is a highly accomplished researcher with over 100 original research papers, 50 review articles, and more than 15 book chapters to his name. He is also the holder of 4 patents. Dr. Guignabert has been invited to speak at numerous national and international conferences and is highly regarded in his field. In addition to his research, Dr. Guignabert serves as an Associate Editor of the European Respiratory Journal. He is also a dedicated mentor and has guided multiple MD and Ph.D scientists, many of whom have gone on to have productive and well-funded independent careers.

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