M/F, CDD 30 months, IDF : Genomics and epigenetics of individual radiosensitivity

A postdoctoral position is offered  in the research laboratory LGRK from the François Jacob Institute of CEA. The IBFJ is focused on human health, and notably genomics, radiobiology, and innovative therapies of human diseases.  LGRK is working in the field of innovative stem cell therapies and personalized radiotherapy. 

MT Martin is the head of LGRK (Laboratory of Genomics and Radiobiology of Keratinopoiesis). She has a renown expertise in the field of radiobiology, skin and adverse effects of radiation, notably more than 40 publications on radiation fibrosis, including several with high citation index such as reference 1, cited 658 times. The group is composed of 3 permanent scientists, including N Fortunel, a renown scientist in the field of stem cells and skin, and P Soularue, engineer in genomics, and 3 technicians. In Evry Genopole, various technological platforms are available (cell imaging, animal facilities, mass spectrometry), and at CEA (“omics, flow cytometry, radiation facility).

References

1. Michèle Martin, Jean-Louis Lefaix, Ph.D., Sylvie Delanian. TGF-β1 and radiation fibrosis: a master switch and a specific therapeutic target? Int J Radiat Oncol Biol Phys. 2000 May 1;47(2):277-90. PMID: 10802350. Citation index : 658 times.

LGRK is working in the field of innovative therapies involving stem cells and personalized radiotherapy. In the latter field, the group is in charge of genomic and epigenomic studies of a cohort of radiosensitive patients, having developed severe complications after radiotherapy. 15% of radiotherapy patients develop such complications, and notably radiation fibrosis. The aim is to develop new prognostic markers of hypersensitivity and to characterize underlying mechanisms. 

In the frame of an ANR contract (INDIRA), our team is in charge of genomic and epigenomic studies of a cohort of radiosensitive patients, which has been set up by INSERM Lyon (Granzotto, IJROBP, 2016)). The aim is to develop new markers of hypersensitivity based on whole exome and RNA-sequencing (CEA genome institute), and to characterize the underlying mechanisms. Genes of the sonic hedgehog pathway and long non codind RNAs are the first identified candidates from sequencing data obtained for 135 patients. The candidate will be responsible for the validation of selected coding and non-coding markers.

References

Granzotto et al. Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity. IJROBP, 2016 Mar 1;94(3):450-60. doi: 10.1016/j.ijrobp.2015.11.013. Citation index: 35.

Recent publications of LGRK, in the field related to the proposal.

. A Vulin, M Sedkaoui, S Moratille, N Sevenet, P Soularue, O Rigaud, L Guibbal, J Dulong, P Jeggo, JF Deleuze, J Lamartine and MT Martin. Severe PATCHED1 deficiency in cancer-prone Gorlin patient cells results in intrinsic radiosensitivity. Int J Radiat Oncol Biol Phys, 2018, Oct 1;102(2):417-425. doi: 10.1016/j.ijrobp.2018.05.057. PMID: 30191873.

. MT Martin, A Vulin, JH Hendry. Human epidermal stem cells: role in skin reactions and carcinogenesis from radiation. Mutation Research, 2016, 770, 349-368. doi: 10.1016/j.mrrev.2016.08.004. PMID: 27919341.

. O. Niwa, M.H. Barcellos-Hoff, R.K. Globus, J.D. Harrison, J.H. Hendry, P. Jacob, M.T. Martin, T.M. Seed, J.W. Shay, M.D. Story, K. Suzuki, S. Yamashita. ICRP, 2015. Stem Cell Biology with Respect to Carcinogenesis Aspects of Radiological Protection. International Commission on Radiological Protection Publication 131. Ann. ICRP 44(3/4),  2015, Sage Ed.  doi: 10.1177/0146645315621849. Epub 2016 Mar 8. PMID: 26956677

- Marie M, Hafner S, Moratille S, Vaigot P, Mine S, Rigaud O, and Martin MT. FGF2 mediates DNA repair in epidermoid carcinoma cells exposed to ionizing radiation. Int J Radiat Biol, 2012, Oct;88(10):688-93. Epub 2012 Jul 20.  Epub 2012 Jul 20.PMID: 22732006.

- Harfouche G and Martin MT. Radiosensitivity of stem cells in normal tissues: a balance between tissue homeostasis and genomic stability. Mutation Research Reviews, 2010, 704: 167–174. doi: 10.1016/j.mrrev.2010.01.007. Epub 2010 Feb 1. PMID: 20117235.

- Harfouche G, Rachidi W, Vaigot P, Rigaud O, Moratille S, Marie M, Lemaitre G, Fortunel NO and Martin MT. FGF2 signaling is critical for DNA repair in human keratinocyte stem cells. Stem Cells, 2010, 28:1639–1648. doi: 10.1002/stem.485. PMID: 20681019.

Candidates should hold a PhD or equivalent degree with experience in computational genomics, molecular genetics and cell biology. The biological skills required are in cellular modelisation and molecular characterization of candidate genes.  Evidence of expertise by scientific publications in peer-reviewed journals will be required.

The ANR project started by the end of 2018, the position is thus immediately available, after CEA employement procedures.

Major aims: demonstration that one coding candidate gene and one long non coding RNA are related to individual radiosensitivity, and publication.