The consortium of the RISK-IR project brings together expertise from 13 research groups of 10 institutions from 7 European countries.
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The Alternative Energies and Atomic Agency Commission (CEA) is a French governmental institution operating in four major fields: energy, defence and security, information technologies and health technologies.
The CEA’s Life Sciences Division combines basic research and applied technology research to provide key insights in energy and healthcare. DSV research in radiobiology and nuclear toxicology aims at determining the impact of nuclear industry on humans and the environment. The CEA’s Life Sciences Division plays a full role in European research, and is a founding member of MELODI, with a strong track record of contributions to EC low dose risk research, including involvement in the FP7 EURATOM project DoReMi.
Laboratory of Genomics and Radiobiology of Keratinopoiesis (LGRK)
Group leader: MT Martin received her Ph.D. at Paris VI University, France, in 1991, and she has developed her research work in the field of radiation biology of the skin at CEA, where she is currently a research director at the head of the Laboratory of Genomics and Radiobiology of Keratinopoiesis (LGRK). She has more than 60 regular articles in international journals with peer review. Since 2001, she specialized in human epidermis stem cells, studying stem cell functions in homeostatic conditions as well as stem cell alterations during the early events of skin carcinogenesis. MT Martin has a long experience of collaborative work within national and international contracts, including 6 EU contracts (five Euratom and one Health funded). She has collaborated with several private companies and benefited from 6 private grants. She recently coordinated a French ANR project, ‘Low dose Radiosensitivity of human skin stem cells’. She has been involved in several advisory roles on stem cells, at the French Senate and Assemblée Nationale. Since 2010, she is a counselor for life sciences at CEA direction (Higher-Commissioner C Césarsky). She is solicited for reviewing submissions by several per-reviewed journals as well as by National, European and International funding agencies. Since 2008, she participates to the ICRP Committee 1 task group on Stem cells and carcinogenesis.
The team: The laboratory is composed of 3 scientists, one engineer and 2 technicians. The first research axis aims at dissecting stem-ness and self-renewal in human skin stem cells. The role of the TGFb pathway in these processes is deeply investigated; Nicolas Fortunel is the CEA key scientist on this topic. He is involved in stem cell biology and skin research, and has more than 20 relevant publications. The second axis explores genomic instability in skin stem cells exposed to genotoxic stresses. The group published several articles on the effects of low dose of ionizing radiation. Recently stem cell responses to radiation were explored. MT Martin’s group has shown that stem cells are radioresistant, and that these cells have developed specific strategies to resist to radiation, including fast DNA repair and specific stress signalling. Odile Rigaud is the CEA key scientist on this topic. She is a radiobiologist, well known in the field of radiation low doses effects, and notably radioadaptation, and she published 40 regular articles.
Research laboratory on Repair and Transcription in Stem cells (LRTS)
The research Laboratory on Repair and Transcription in Stem cells (LRTS) is part of the CEA Institute of Cellular and Molecular Radiobiology that is located at Fontenay-aux-Roses and Evry. Research in progress at the iRCM is focused on the in vitro, ex vivo and in vivo effects of irradiation. It includes studies of the effects of low and high doses of radiation and contamination from radioactive elements, on DNA lesions and repair mechanisms, and on the cellular responses to the associated diseases (cancer and non-cancer-related diseases, hereditary effects, etc.). The LRTS has several research projects on normal hematopoiesis and on leukemia. On normal hematopoiesis, this team’s projects are focused on the effects of low and high doses and dose rates of radiations on the biology of hematopoietic stem cells, on the role of Nrf2 in the response of hematopoietic stem cells to low doses of irradiation and on the functions of a nuclear co-regulator, TIF1g, in adult hematopoiesis. On leukemia, this team’s projects are focused on the pathways that are activated by TAL1 in human T-ALL and on the in vivo imaging of a leukemia development.
Paul-Henri Romeo, after a scientific education at Ecole Polytechnique, received his PhD in 1983 and carried out a post-doctoral fellowship in molecular biology at the NIH from 1985 to 1988 in the laboratory of Dr. M. Zasloff. Appointed as a Director of Research at Inserm in 1989, he is presently at the head of the Inserm Unit 967 (Stem Cells and Radiation), the Director of the Institute of Cellular and Molecular Radiation biology at the CEA (CEA/DSV) and the Head of the ITMO “Immunology, Hematology and Pneumology”, one of the ten research institutes that coordinate research in biology in France. He has coordinated several research projects supported by ANR, ARC and Ligue contre le Cancer and participates in an Inca funded project on the effects of high dose- rates on hematopoiesis. His main research interests are normal and pathological hematopoiesis, hematopoietic stem cells and effects of internal or external irradiation on the hematopoietic stem cells. With respect to normal and pathological hematopoiesis, he studied the role of master trans-acting factors such as TAL1 or TIF1γ in the regulation of normal and pathological erythropoiesis particularly the roles of these proteins in hematopoietic stem cells and in T-ALL (T cell leukemia). Recently, he studied the effects of tritium contamination of hematopoietic stem cells both in vitro and in vivo. As head of the institute of Cellular and Molecular Radiation biology (CEA/DSV), he oversees research that focuses on understanding the effects of radiation and contaminations at the molecular, cellular and animal levels and at the development of new strategies to treat human diseases caused by irradiation and contamination. This research combines fundamental studies on animal models such as yeast or bacteria and studies on mice or on human pathology and covers all aspects of biological effects of irradiation or contamination from the initial cellular events that occurs immediately after irradiation or contamination to very long term effects such as cancer. He is solicited for reviewing submissions by several per-reviewed journals including Blood, J Exp Med, EMBO J., Nature etc...as well as by National, European and International funding agencies. He was awarded the Montyon prize from the French Academy of Sciences, the Paris prize of the Ligue National contre le Cancer and the Rosen prize of the French medical research foundation in 2008.
The Laboratory for Stem cells in Hematopoiesis and Leukemia (LSHL)
This laboratory is part of the Institute for Cellular and Molecular Radiobiology. The LSHL members are 10, including 4 researchers (including the PI : Dr F Pflumio) + 1 post-doc + 1 technician+ 4 PhD students. The group has been focusing its research on two major aspects : (1) understanding the biology of human haemopoietic stem cells (HSC), in particular investigating the role of transcription factors such as SCL/TAL1 on self-renewal/maintenance and differentiation of human HSC and (2) delineation of the role of this same protein in leukemia development as the protein is implicated in human T-ALL. This led us to develop a whole area of expertise in the technical manipulations of human HSC and leukemias from patients. As a consequence many assays such as differentiation, proliferation, transplantation and gene modification assays have been successfully developed by the team that are now recognized worldwide and international collaborations are running based on the general knowledge of the team in terms of human cell manipulation. As part of the IRCM, the laboratory is getting interested in looking at the consequences of low doses irradiation on human HSC biology, especially in combination with oncogene mis-expression during differentiation.
Our Institute has developed several common facilities including FACS sorting (MoFlow and Influx machines) and analysing (LSRII and Facscalibur x2), confocal microscopy, animal colony including immune-deficient NSG mice, irradiation facilities (three irradiators available one of them being dedicated to low doses), laboratories dedicated to lentiviral vector productions (L3) and transduction and several L2 laboratories for human cell culture. The LSHL team has regularly access to human cord blood from UCB banks. Adult mobilized blood will be obtained through a collaboration with the établissement Français du Sang in Bordeaux.
Francoise Pflumio is the PI of LSHL. She will contribute to activities in WP3 and is Partner 5. She is a research director of the french equivalent of NIH, called Institut National de la Santé et de la Recherche Scientique (INSERM). She defended a PhD in Immunology in Strasbourg, France in 1990. Spent 3 years in post-doc in the Laboratory of Pr John Dick, in Toronto/Canada until the end of 1993. She performed a second post-doc with Dr L Coulombel and W Vainchenker, Villejuif, France until 1996. She got a permanent position as a junior scientist in INSERM in 1996 and got a research director position in 2008. She has more than 40 relevant publications.
Laboratory of Radiopathology (LRP)
Group Leader: François Boussin has more than 60 relevant scientific publications. He has a track record of research in the fields of DNA damage response and radiation biology using cellular and animal models. His team has recently reported the intriguing lack of G1/S checkpoint in fetal neural stem cells and, in a submitted manuscript, has analyzed the consequences of the absence of a fully functional homologous recombination for irradiated neural stem cells. In another submitted manuscript, his team reports the critical role of TGFß for the radiation-induced long-term impairment of adult neurogenesis. Besides, he has reported the first example of human glioma stem cells maintaining their telomeres through mechanisms of telomere maintenance alternative to telomerase and the consequences of these mechanisms for the radiation-response of cancer cells. He has strong experience in collaborative works with pharmaceutical groups or academic laboratories. He is currently involved in several collaborative studies financed by INCA and ANR. He has recently coordinated an ANR project focusing on the response of neural stem cells to ionizing radiation addressing cellular and molecular mechanisms as well as behavioral consequences for the irradiated mice.
The Team: The team is composed of 7 scientists and 1 technician. Marc-André Mouthon (more than 30 publications) is specifically in charge of the characterization of DNA damage response of adult neural stem cells. The team has developed several models of irradiation of the fetal and adult mouse brain including focal irradiation of neurogenic niches. The team has a strong expertise in brain histology and has also set up various techniques to investigate cell cycle progression and interkinetic nuclear migration of neural stem cells based on EdU and BrdU both ex vivo and in brain slice cultures. In addition the team has developed different methods of purification and culture of neural stem cells from foetal or adult tissues as well as methods for engraftment of normal and cancer neural stem cells in the mouse brain. The team has also a strong expertise in cytogenetics.