The Martin’s lab is seeking a talented computational scientist for a postdoctoral fellowship to study the cellular and molecular heterogeneity and functions of mononuclear phagocytes in human digestive diseases using high dimensional single-cell technologies.
General context
The objective of the Martin’s lab is to harness the power offered by new single-cell technologies to deconvolute the role and regulation of mononuclear phagocytes in pathogenic responses driving tissue lesions in patients affected by digestive diseases. Our ultimate goal is to enhance the rational for future drug and biomarker discovery. In particular the clinical benefit of targeted immunotherapy in IBD and gastric cancer has remained limited to a subset of patients and the use of standard of care imaging and/or histological diagnostic assays has failed to confidently stratify potential responders from non-responders. Accordingly, none of the targeted immunotherapy approved to treat patients are provided with decision algorithms to maximize therapeutic responses. Besides, the poor understanding of disease pathophysiology significantly limits the identification of relevant targets. There is therefore an urgent need to gain a better understanding of the cellular programs in normal and lesional human digestive tissues.
Project
The applicant will be involved in leading the computational analysis in two funded projects aiming at characterizing MNP molecular programs and cellular interactions in tissues from patients with ileum Crohn’s disease, or with gastric precancerous and cancerous lesions. Using state-of-the art machine-learning and exploratory data analysis tools, the study will dissect single-cell RNA sequencing, single-cell ATACseq and spatial transcriptomics datasets. It will combine profiling microenvironments in healthy and diseased tissues with analysis of Electronic Medical Records. Both projects involve close interactions with Gastrointestinal clinicians, pathologists and gut immunologist in Nantes (bi-monthly meetings in the context of the Nantes IBD-NeXT cluster for instance (https://next-isite.fr/ibd-next/).
In Crohn’s disease our main objective is to characterize how pathogenic MNP populations drive resistance to current targeted therapies and contribute to stenotic complications through their interactions with stromal cells. This project is in direct follow-up of our previous study, which described the MNP-organized GIMATS response in patients resisting anti-TNF antibodies (Martin JC, Cell, 2019). This project is funded by ANR and NExT.
In gastric cancer, our main objective is to understand how the MNP molecular landscape is progressively shaped to promote tumor growth along the stepwise progression of precancerous lesions to tumor. This is a new project funded by ARC, which benefits from a unique cohort of patients built at CHU de Nantes.
Martin’s lab people involved in these projects:
– Gaelle Beriou, PhD – permanent research engineer
– Lucas Bruselle: research technician
– Thomas Laurent: PhD student
– Nicolas Chapelle: MD (digestive oncologist) – PhD student
– Pr Tamara Matysiak-Budnik: MD-PhD (digestive oncologist) – Attending Physician
International scientific collaborators on these projects:
– MNP biology: Pr Miriam Merad (Icahn School of Medicine at Mount Sinai, New York, NY)
– Computational biology: Dr Ephraim Kenigsberg (Icahn School of Medicine at Mount Sinai, New York, NY)
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