Last update on January 2018
The Radiobiology of Medical Exposure Laboratory (LRMed, formerly L3R and LR2I) is located in Fontenay-aux-Roses and Fabien Milliat is head of the laboratory. LRMed was set up to further our understanding of the biological mechanisms involved in the onset and development of lesions in healthy tissue caused by exposure to ionizing radiation, at moderate-to-high dose, used in healthcare to diagnose or treat patients (e.g in radiotherapy) with a view to better predicting, understanding, preventing and treating complications.
Background and research themes
One of IRSN's objectives is to lead research projects aimed at understanding the biological effects of ionizing radiation, including the effects caused by its use in the field of medicine. Over 50% of cancer patients are currently treated using radiotherapy, which, while it is an effective treatment, can, in some cases, cause damage to healthy tissue that comes within the irradiation field. Radiation-induced damage occurs as a result of a sequence of complex, integrated biological responses involved in the onset, development and chronicity of tissue lesions. The endothelium appears to be one of the key compartment in the kinetics of these events, and one of LRMed's objectives is to investigate potential causal links between endothelial cell damage/dysfunction and progression to late-onset tissue damage. Furthermore, LRMed develops treatment strategies designed to limit the evolution and progression of severe radiation-induced lesions.
Research at LRMed aims to:
- Better understand the mechanisms at molecular, cellular and tissue level involved in the biological and physiopathological effects on healthy tissue as a result of external exposure to moderate-to-high dose radiation as used in different irradiation protocols used in the field of medicine;
- Develop new tools to improve the diagnosis and prognosis of radiation-induced damage and work toward their clinical use;
- Develop new concepts and models for predicting the risks related to radiotherapy;
- Perform experiments to validate treatment strategies, especially cell therapy, for the medical treatment of severe radiation-induced lesions caused by external exposure in the field of medicine;
- Carry out research on the mechanisms of action of such treatments, and work toward their clinical use.
LRMed carries out in vitro and in vivo studies to investigate radiation-induced effects on healthy tissue. The laboratory employs an integrated “Systems Biology” approach (combining Omics Biology, Mathematics and Computational Biology) to fully understand the vascular compartment's response to irradiation. For in vivo experiments, LRMed 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). LRMed also seeks to identify whether certain physiological and pathological functions of the endothelium and related molecular pathways are involved in the continuum between acute response and late tissue toxicity. Research is thus focused more specifically on inflammatory and immune system responses, the roles of molecules involved in fibrinolysis (PAI-1), in the response to hypoxia (HIF-1), in endothelial-mesenchymal transition, as well as on post-translational modification (glycosylation) of endothelial proteins. LRMed also implements multiparameter molecular and functional RBE (Relative Biological Effectiveness) measurement, thereby enhancing IRSN's assessment capabilities in predicting the risks relating to new radiotherapy techniques.
The other research priority at LRMed is to develop prophylactic and/or curative treatment strategies for severe radiation-induced damage to the digestive system and bones. The research carried out to this end focuses on the use of cell therapy. To this end, LRMed studies the potential effectiveness of mesenchymal stromal cell (MSC) therapy combined with biomaterials and/or other (pharmacological, probiotic, etc.) agents able to enhance the beneficial effects of MSC therapy. For this research, LRmed develops preclinical irradiation models to assess treatment outcomes (gastrointestinal functions and gut-brain axis) and understand the mechanisms of action, including the role of vascular, inflammatory and immune system responses.
Fabien Milliat, Head of LRMed and Researcher (authorized research supervisor)
Valérie Buard, Technician
Alain Chapel, Researcher (authorized research supervisor)
Christelle Demarquay, Technician
Agnès François, Researcher (authorized research supervisor)
Olivier Guipaud, Researcher (authorized research supervisor)
Christine Linard, Researcher (authorized research supervisor)
Noëlle Mathieu, Researcher
Vincent Paget, Researcher
Alexandra Semont, Researcher
Claire Squiban, Technician
Georges Tarlet, Technician
Frédéric Soysouvanh, Doctoral student (2015-2018)
Mariam Ben Kacem, Doctoral student (2016-2019)
Annaïg Bertho, Doctoral student (2016-2019)
Alexia Lapière, Doctoral student (2016-2019)
Partnerships and research networks
LRMed works in collaboration with the following French partners:
- The University Hospitals in Rouen and Nantes
- The Universities of Evry, Lille, and Rouen
- CRI Bichat (Center for Research on Inflammation)
- Beaujon Hospital
- Gustave Roussy Cancer Campus
- Faculty of Pharmacy at Chatenay-Malabry
- Percy Military Hospital
- Cell Therapy Unit, Armed Forces Blood Transfusion Center (CTSA)
- Hematology Department, Saint Antoine University Hospital
And the following international partners: the Cleveland Clinic Lerner Research Institute, the University of Los Angeles, the Flemish Catholic University of Leuven (KU Leuven) and the Terry Fox Laboratory Vancouver.
LRMed is the host laboratory for the "Physiology, Physiopathology and Therapy" (P2T) doctoral School (UPMC, ED 394) of Pierre et Marie Curie University and the Cancerology doctoral school of Paris-Saclay University.