I am currently an Assistant Professor (PhD - CR1 INSERM / Univ. Paris-sud and Université Paris-Saclay) at INSERM UMR_S 999 headed by Pr Marc Humbert (Le Plessis-Robinson, France). My research interests seek to provide a better understanding of pulmonary-endothelial cells (ECs) in idiopathic Pulmonary Hypertension (iPH). I started my postdoctoral training in the Department of Physiology at the University of Paris-Est, Créteil, France. During that time, I actively collaborated with leading experts in the field of cardiovascular development and disease at the Stanford University School of Medecine, Stanford, California, USA. I spent two years in Dr. Marlene Rabinovitch’s Cardiopulmonary Research Laboratory where I studied the role of the peroxisome proliferator-activated receptor (PPAR)γ, the microtubule associated protein ligh chain 3 (LC3), and the bone morphogenetic protein receptor (BMPR)-1A (a co-receptor of BMPRII) in pulmonary vascular remodeling and Pulmonary Hypertension. On my return in France, I joined the Marc Humbert Research Laboratory as a researcher and pursue my own research interests focused on the aberrant pulmonary EC phenotype in PAH and on the identification of new molecular targets to normalize this abnormal endothelial phenotype in PAH. Since 2010, I am leading a research team entitled 'Cellular and Molecular bases of Pulmonary Endothelial Dysfunction in PAH' currently composed of 2 engineers and 2 post-doc, 3 Ph.D and 3 Master students (http://www.u999.u-psud.fr/en/unit-u999/research-topics/pah-physiology-topics.html). Our research group was recently awarded by the Label "Equipe FRM 2015" of the Fondation Recherche Médicale.
"His research is supported by grants from the French National Research Agency (ANR Starting Grant 2012 "EPINE ": ANR_12_JSV1_0004_01), the Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM VIGIAPATH project) and the Fondation pour la Recherche Médicale (Equipe FRM label 2015).
Current Research and Scholarly Interests: http://www.u999.u-psud.fr/en/unit-u999/research-topics/pah-physiology-topics.html
My primary research for the past several years seeks to: (1) Provide a better understanding of the role played by ECs in pulmonary vascular 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 research group 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 (Le Hiress et al. Am J Respir Crit Care Med 2015); 2) an aberrant hyper-proliferative and apoptosis resistant phenotype (Tu et al. Am J Respir Cell Mol Biol 2011); 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, monocyte chemotactic protein (MCP)-1 (Ricard et al. Circulation 2014; Le Hiress et al. Am J Respir Crit Care Med 2015); 4) an excessive production and secretion of various key growth factors including fibroblast growth factor-2 (FGF-2; basic FGF) (Tu et al. Am J Respir Cell Mol Biol 2011; Tu et al. Am J Respir Crit Care Med 2012 ; Ricard et al. Circulation 2014), angiotensin-II (Ang II) (de Man et al. Am J Respir Crit Care Med 2012), and leptin (Huertas et al. Eur Respir J 2012 and Huertas et al. Eur Respir J 2015).
The underlying mechanisms remain unknown and substantial work remains to be done. Our research interests focuses on the mechanisms by which pulmonary ECs interact with their environment. Firstly, we are studying the importance of the MIF/CD74 signaling pathway at the crossroad of Inflammation and Endothelial dysfunction (ANR jeune chercheur 'EPINE'). Secondly, we are exploring the endothelium/ pericyte interactions as well as the endothelial/ immune cell interactions (with regulatory T cells (Tregs) in particular) (Equipe FRM label 2015 of the Fondation Recherche Médicale). Finally, we are studying the mechanisms of certain iatrogenic agents, such as drugs, on endothelial dysfunction (project ANSM 'VIGIAPATH').
Scientific Focus: Pulmonary hypertension (PH) – Pulmonary vascular remodeling – Endothelial dysfunction – Endothelial communications – Pericyte – Endothelial cell – Growth factors – Animal models.