Postdoctoral position in high-throughput data analysis, OncoImmunology field INSERM research program

Postdoctoral position in high-throughput data analysis, OncoImmunology field INSERM research program

Inserm

Paris, France

Presentation of the Research team and Scientific/clinical environment: The ‘Microsatellite Instability and Cancer’ research team has been created on January 1st, 2006. It is located in the center of Paris, in the Saint-Antoine Research Centre (Saint-Antoine Hospital). The topics for this research lab are focused on the study of mismatch repair (MMR)-deficient human tumors displaying microsatellite instability (MSI). Since funded, this lab has established an extensive clinical and research network, leading to the development of an ambitious research program focused on cancer genetics. It published widely on MSI tumors in high-ranked basic and clinical journals. Our lab has been recently very positively evaluated by Sorbonne University, INSERM and is largely supported number of institutions such as National Institute of Cancer (INCASIRIC 2018), French League Against Cancer (label and grants), ARC Foundation for Cancer Research.
Context and Job description : The MSI-driven pathway to cancer leads to the synthesis of aberrant and potentially immunogenic neo-antigens by the tumor cells. A likely consequence is that MSI tumors are highly infiltrated with cytotoxic T-cell lymphocytes (CTLs) that are thought to constitute strong and independent predictors of relapse and survival in tumors regardless of their molecular phenotype (MSI or MSS). Recently however, it was shown that MSI tumors were likely to persist in such an hostile immune microenvironment because of immune-escape due to dramatic co-overexpression of immune checkpoint (ICK)-related proteins. Based on these findings, MSI status was shown to predict clinical benefit from ICK blockade therapy with an anti-PD-1 inhibitor in a fraction of patients with metastatic neoplasm. Recent analysis of the expression level of genes encoding ICKs in two independent cohorts of CRC treated with standard care (stage 1 to stage 4 CRC; 232 MSI, 971 MSS) in our team highlighted that ICK overexpression was associated with significantly worse prognosis in MSI tumors only (e.g. not in MSS CRC), independently of tumor staging or CTL infiltrates (Immunoscore).
As a project, the candidate will aim to further establish how the immune contexture of MSI tumors has a crucial role during MSI tumorigenesis from both a pathophysiological and clinical point-of-view. In particular, he/she will try to better design the exact perimeter of future immunotherapy involving antibody blockade of ICKs and resistance to these molecules in MSI CRC patients. Several large cohorts of MSI/MSS CRC patients including stage 3 or stage 4 tumors treated by standard care (untreated with immunotherapy; MOSAIC clinical trial) and also stage 4 MSI CRC treated with immunotherapy (Ac anti- PD-1 +/- anti- CTLA-4; NIPICOL clinical trial coordinated by our lab) are already available for the project. Somatic mutational events and those participating to the so called MSI-driven mutational events that frequently accumulate in MSI tumor cells and deeply influence anti-tumor immunity and the expression of ICK molecules will be assessed by exploiting both Exome and RNA sequencing data already available for this project (e.g. mutations affecting neo-antigens presentation by tumor cells, …).
Requirements : Candidates are required to have a PhD in Immunology and strong background in biostatistics, computational biology or bioinformatics. Experience in high-throughput genomics data analysis, programming skills (in languages such as R or python), and strong cancer biology interest or background are required.
Contact details : please contact Alex Duval (phone : +33 1 49 28 66 80, e-mail : alex.duval@inserm.fr) and Vincent Jonchere (e-mail : vincent.joncherel@inserm.fr) . When applying, please ensure you include a CV, motivation letter, list of publications and the names and addresses of at least three persons as references.

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Postdoctoral position in high-throughput data analysis, OncoImmunology field INSERM research program