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Enhancing Nuclear Safety


Research

Research units

Radiobiology of Medical Exposure Laboratory (LRMed)


Last update on July 2019

 

The Radiobiology of Medical Exposure Laboratory (LRMed) 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 (PRISME clinical trial).


Research areas

 

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, Statistics and Computational Biology) to fully understand the vascular compartment's response to irradiation (ROSIRIS program). 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, senescence, the roles of molecules involved in fibrinolysis, in the response to hypoxia (HIF-1), in endothelial-mesenchymal transition, as well as on post-translational modification (glycosylation) of endothelial proteins. In addition, thanks to efficient irradiation methods (LINAC and SARRP), LRmed develops complex pre-clinical models of localized irradiation as close as possible to new treatments and current radiotherapy techniques (i.e. stereotactic radiotherapy) in order to study the effects of doses, volumes and splits.


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 in vitro models of "organoids" and 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.



Research team

 

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

Emilie Lebraud, post-doc researcher

Ian Morilla, researcher (mathematician, bio computer scientist)

Mariam Ben Kacem, Doctoral student (2016-2019)
Annaïg Bertho, Doctoral student (2016-2019)
Alexia Lapière, Doctoral student (2016-2019)
Ségolène Ladaigue, Doctoral student (2018-2020)
Clément Brossard, Doctoral student (2018-2020)
Sarah Braga Cohen, Doctoral student (2019-2021)
Mallia Geiger, Doctoral student (2019-2021)
Lydia Bensemmane, Doctoral student (2019-2021)


 

Partnerships and research networks

 

Internally, LRMed collaborates with LDRI and LRAcc as part of the ROSIRIS program.


Externally, LRMed works in collaboration with the following partners:

  • The University Hospitals in Nantes, Regenerative Medicine and Skeleton, INSERM UMR 1229
  • The Universities of Evry, Lille, and Rouen
  • CRI Bichat (Center for Research on Inflammation INSERM U1148)
  • The Translational Vascular Research Laboratory (LVTS Inserm U1149)
  • Mulhouse Institute of Materials Science, IS2M - UMR CNRS 7361 - UHA
  • UFR Pharmacy, IBMM, Montpellier
  • Complex Materials and Systems Laboratory (UMR 7057), University of Paris-Diderot 
  • Rouen University Hospital
  • Beaujon Hospital
  • Necker Hospital
  • Gustave Roussy Cancer Campus (INSERM U1030)
  • Faculty of Pharmacy at Chatenay-Malabry
  • INRA
  • Percy Military Hospital
  • Cell Therapy Unit, Armed Forces Blood Transfusion Center (CTSA)
  • Hematology Department, Saint Antoine University Hospital
  • CEA


LRM​​ed is involved in several collaborative research projects funded by the ANR (ANTHOS, iXBONE, GIPSIS​ projects) and CNIB (AAP PLBIO 2017, 2018).


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.


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Research program

Contact

Fabien Milliat, head of laboratory

 

IRSN
PSE-SANTÉ/SERAMED
Radiobiology of Medical Exposure Laboratory (LRMed)
BP 17
92262 Fontenay-aux-Roses Cedex

Tel : +33 1 58 35 91 60

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