Postdoctoral Fellow in the Cancer Research Center of Toulouse Cancer Research Center of Toulouse, Institute for Research in Digestive Health
Job Summary:A postdoctoral position is available in INSERM U1037 - CRCT “Cancer Research Center of Toulouse”, France. Our research team is located at the Toulouse Oncopole. The trainee will be supervised by Corinne Bousquet (DR2 INSERM) in the CRCT Team 6 (co-directed by Drs Stéphane Pyronnet and Corinne Bousquet), and in close collaboration with the group of Nathalie Vergnolle and Audrey Ferrand (IRSD “Institut de Recherche en Santé Digestive” - INSERM U1220, Toulouse), ,that is specialized in 3D-organoïd development. The proposed work aims at exploring whether the 3D polarized organization of tumor organoïds facilitates tumor cell invasion and metastasis, and how Cancer-Associated Fibroblasts cooperate together with immune responses to foster early metastasis, a main cause of rapid death for PDAC patients. Job Description:Pancreatic ductal adenocarcinoma (PDA) remains a highly lethal malignancy. Up-to-date, therapeutic strategies aiming at targeting pancreatic cancer cells have failed. We hypothesized that such pitfall is due to the functional heterogeneity of this tumor which comprises both cancer and stromal cells. To reach efficacy with chemotherapies, our recent findings support the idea that stroma has to be co-targeted. PDA stroma is characterized by the extreme abundance of cancer-associated fibroblasts (CAFs) and by the recruitment of immunosuppressive cells, that promote cancer cell metastasis and chemoresistance, and compromise immune antitumoral responses, respectively. Our team is expert in pancreatic adenocarcinoma biology, focusing more specifically on the role of the microenvironment and of CAF on tumor cell metastasis and chemoresistance. We have recently uncovered a pharmacotherapy that, when combined with the gemcitabine chemotherapeutic PDA reference drug, abrogates CAF's prometastatic and chemoprotective features by inhibiting synthesis and secretion of growth and chemoprotective factors by CAFs (Duluc et al, EMBO Molecular Medicine 2015, Moatassim-Billah et al, Oncotarget 2016). Testing this novel drug combination on immunocompetent models is necessary. Genetically-engineered mouse models (GEMM) mimicking PDA, which our team also use (Chalabi-Dchar, Gastroenterology 2015) are appropriate but expensive, time-consuming, poorly (timely) reproducible, and difficult for in vivo real-time imaging. These pitfalls are overcome when using syngeneic orthotopic allograft of tumor organoïds (grown in three dimension (3D) and isolated from GEMM PDA tumors), and which, in contrast to 2D-grafting, faithfully recapitulates PDA from inception to metastasis. Our present project aims not only at developing an innovative approach to set up 3D co-cultures of CAF and tumor organoïds, but also at using this model to understand how the primary tumor in its 3D polarized organization becomes immunosuppressive, and which role CAFs play in the acquisition of immunosuppression skills in PDA organoïds / CAF co-cultures. The contract fund is for 15 months (starting October 1rst, 2016), with a possibility of extension by the candidate (application to french funding agencies) with the support of the laboratory. Post-Doctorate Profile:We are seeking for a highly motivated post-doctoral fellow with a good track record. Ideally, the candidate should have validated a Ph.D. or a first post-doctoral experience, with at least one publication as a first author (less than 3 years after completing his/her-Ph.D.). Ideal candidate profile:
Presentation of CRCT - INSERM U1037Team 6 (http://www.crct-inserm.fr/06-s-pyronnet-c-bousquet-protein-synthesis-secretion-in-carcinogenesis-548.html) entitled " Protein synthesis & secretion in carcinogenesis " is located at the Cancer Research Center of Toulouse (http://www.crct-inserm.fr), a modern building inaugurated in 2014 with dedicated technological expertise (www.poletechno-crct.inserm.fr/en/), and which just opened a brand new animal facility (http://anexplo.genotoul.fr). Translational research at CRCT is facilitated by its proximity with the IUCT (Institute University of Cancer Toulouse) and by dedicated physicians working in CRCT research teams. Main research field:Cancer Biology and immuno-oncology Biological sciences / Medical sciences JOB DETAILType of contract : Temporary APPLICATION DETAILSEnvisaged job starting date : October 1st, 2016 Application deadline : September 30th, 2016 Application e-mail : corinne.bousquet@inserm.fr Candidates should send a cover letter describing their research interests, a CV including a list of publications and the names/emails of at least two references
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