The L3R Radiobiology and Radiation Disease Research Laboratory of the IRSN (Institute for Radiological Protection and Nuclear Safety) is located in Fontenay-aux-Roses, France, and headed by Fabien Milliat. Its main objective is to gain an understanding of the pathophysiological mechanisms involved in the onset of complications after radiotherapy.
One of the goals of the Institute is to conduct research projects aimed at understanding the biological effects of ionizing radiation, particularly in the context of its medical use. More than 50% of all cancer patients currently receive radiation therapy. While this treatment is effective, in some case, it can cause damage to healthy tissues in the irradiated field. Radiation-induced damage is the result of a sequence of complex, integrated biological responses involved in the onset, progression, and chronicity of tissue damage. The endothelium appears to be the most important compartment in the kinetics of these events, and one of the objectives of the L3R is to investigate potential causal links between endothelial damage/dysfunction and progression to late tissue damage.
The missions of the L3R are:
- to understand the biological (molecular, cellular and tissue) effects observed in healthy tissue as a result of external exposure to different types of radiation and different irradiation configurations in normal and accidental situations;
- to provide tools facilitating the diagnosis and prognosis of radiation damage and contribute to their clinical transfer;
- to develop predictive models of the risks associated with these radiation-induced effects;
- to identify new therapeutic targets for the treatment of these radiation-induced effects.
The L3R carries out in vitro and in vivo studies to investigate radiation-induced effects on healthy tissue. Thus, one of the focal areas of the lab is the use of a systems biology approach ("omics" biology interface, mathematics and bioinformatics) in order to gain a comprehensive understanding of the response of the vascular compartment to irradiation.
In vivo, the L3R implements and uses transgenic mouse models to specifically study the role of the vascular compartment in the progression of intestinal and lung tissue damage (Cre-lox approach).
The L3R also aims to determine whether certain physio/pathological functions of the endothelium and related molecular pathways are involved in the continuum between acute response and late tissue toxicity. Thus, some investigations focus more specifically on the inflammatory and immune responses, the roles of molecules involved in fibrinolysis (PAI-1), in the response to hypoxia, in endothelial-mesenchymal transition, or even post-translational modifications (glycosylation) of endothelial proteins.
Finally, the L3R lab implements multiparametric molecular and functional RBE (relative biological effectiveness) measures to strengthen the Institute's expertise capabilities in terms of predicting risks associated with new radiotherapy techniques.
Fabien Milliat, research scientist, HDR (Accreditation to Supervise Research), Head of Laboratory
Agnès François, research scientist, HDR
Olivier Guipaud, research scientist, HDR
Céline Loinard, research scientist
Vincent Paget, research scientist
Valérie Buard, technician
Georges Tarlet, technician
Fanny Caffin, postdoctoral research scientist (2015-2016)
Sonia Selbonne, postdoctoral research scientist (2015-2016)
Elodie Mintet, PhD student (2012-2015)
Cyprien Jaillet, PhD student (2013-2016)
Jérémy Lavigne, PhD student (2014-2017)
Christine Karagoz, Second year Masters student (2015)
The L3R lab has national partnerships with:
- Rouen University Hospital,
- Universities of Evry, Lille, Rouen
- Centre de recherche sur l’inflammation (Center for Inflammation Research), Bichat
- Beaujon Hospital
- Gustave Roussy Cancer Campus
- ENS (French higher education establishment), Paris
And at the international level: Cleveland Clinic Lerner Research Institute, University of Los Angeles, Flemish Catholic University of Leuven (KU Leuven) and the Terry Fox Laboratory Vancouver.
The L3R lab is a Host laboratory of the Physiology and Physiopathology doctoral school (DS 394) of the UPMC Pierre & Marie Curie University).