Hôpital de la Pitié-Salpêtrière
83, boulevard de l'Hôpital
Title of the PhD project:
Characterization of the dynamics of immune cells during low-dose IL-2 treatement in clinical trials using Bioinformatics approaches
The i3 lab is pioneered in the field of low-dose IL-2 (ld-IL2) as a regulatory T cell stimulator for the treatment of autoimmune diseases. Since we first reported positive results from the first worldwide clinical trial investigating ld-IL2 in an autoimmune disease, i.e. HCV-induced vasculitis (Saadoun et al., NEJM2011), ten clinical trials with ld-IL2 have been completed or are in progress. Among them, the LUPIL-2, DIABIL-2 and HEALTHIL-2 clinical trials (which are part of the RHU IMAP project), are purely cognitive double-blind trials that are evaluating the effects of ld-IL2 in patients with Lupus Erythematosus or Type 1 diabetes, and in healthy volunteers.
Through these trials, we aim to dissect IL-2 biology in abnormal or normal balanced immune systems to discover biomarkers of response to IL-2. The ultimate goal is to understand and predict the physiopathological status of patients based on these immune biomarkers.
The main objective of the proposed project is to characterize the phenotypes and functions of leukocytes collected from patients enrolled in LUPIL-2, DIABIL-2 and HEALTHIL-2 clinical trials with a very thorough immunological follow-up. This immune-monitoring consists of 10 flow cytometry panels quantifying each the expression of 16 cell parameters at different time points of the patient’s followup. We will characterize and cross-phenotype immune cells using the methodology developed for non-supervised analysis by our team using SPADE and viSNE cell clustering algorithms. Thanks to these algorithms, we are able to explore in a completely unbiased way immune populations that have been determined automatically, and identify differences between subsets of patients of interest. These new approaches offer great potential for the exploration of the thousands of samples collected in a kinetics manner as part of these trials.
In addition, these results will be we will combine with cytokine expression patterns, inflammatory markers, Treg/Teff TCR repertoire analysis, Treg/Teff transcriptome data and microbiome obtained from the same patients to identify correlates and biomarkers of ld-IL2’s efficacy.
The laboratory is offering a unique interdisciplinary environment, with biologists, immunologists, clinicians, computer scientists and bioinformaticians. The candidates will be based in the i3 laboratory located on the Pitié‐Salpêtrière hospital campus in Paris (13ème).
The expected candidate will justify training in Immunology / Computer Science / Bioinformatics, with interest for Systems Biology. The candidate will benefit from an interdisciplinary environment, including biologists, immunologists, clinicians, computer scientists, and bioinformaticians. This project is part of the laboratory funded projects (LabEx Transimmunom - www.i3-immuno.fr, www.transimmunom.fr.