Genomic instability and human blood diseases

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Research topics & objectives

The laboratory aims to identify the “addictive” molecular alterations present in lymphoid tumours, and particularly the founding mutations of the cancer stem cells (CSC) responsible for relapses/early relapses/resistance to treatment. The research team is testing the inhibition of these cells in “à la carte” in vitro/ex vivo/in vivo preclinical models.

Research topics

Identification of progression biomarkers and new therapeutic targets in lymphomas and acute lymphoblastic leukaemia.

Lymphoma sub-types

  • B-cell lymphomas, including follicular lymphomas
  • Acute lymphoblastic leukaemia (ALL)

Key words

Follicular lymphoma, T-ALL, Oncogenesis, Oncogenic addiction, CSC, Single-cell, -OMICS, CRISPR/CAS screen, Preclinical models, Predictive and prognostic biomarkers

Bertrand Nadel Co-Directeur
Sandrine Roulland Co-Directrice

INSERM U1104

EXPERTISE

BIOLOGICAL TARGETS AND IN VITRO/IN VIVO/EX VIVO MODELS

Targets

  • “Addictive” molecular alterations of lymphoid tumours
  • BCR/TCR signalling
  • Founding mutations of the cancer stem cells (CSC) responsible for relapses
  • c-MYC, PTEN, TAL1 in T-ALL
  • Epigenetics

Models

  • B and T-cell lineages (modification by CRISPR/Cas9)
  • “À la carte” preclinical mouse models (KI/KO/Tg, conditional retroviruses, BMT, chronic long-term immunity, tumour transplantation, PDX)
  • Mouse models imitating the progression of early-stage follicular lymphomas (FL) to equivalent FL structures in situ (FLIS)
  • T-ALL xenograft models in immunodeficient mice from human stem cells
  • Short-term PDX culture ex vivo for molecule screening

BLOOD AND TISSUE BIOMARKERS

Progression biomarkers and new therapeutic targets in lymphomas and acute lymphoblastic leukaemia.

INNOVATING TECHNOLOGY

  • Lenti/Retro-viral manipulation & PDX
  • NGS, OMICS (Attac-seq, ChiP-seq, RNA-seq, scRNA-seq, exome)
  • Single-cell RNAseq / single-cell qPCR & bioinformatics pipelines developed for single-cell
  • CRISPR/CAS9 (editing lineages and CrispR/CAS screen)
  • shRNA
  • Chemograms
  • Multicolour FACS

Platforms & technical resources

  • Single-cell RNAseq (10x Genomics Chromium)
  • Single-cell qPCR (Fluidigm Biomark)
  • L2/3 confinement laboratory (CMF/cell sorting, technical lentivirus production platform)
  • L2-dedicated influx cell sorter
  • Imaging (confocal/two-photon microscopy)
  • Mouse engineering
  • PDX collection of transplantable, biologically characterised and clinically annotated T-ALL

R&D offer

  • Lymphoid tumour expertise
  • Single-cell technology and bioinformatics analysis pipelines expertise
  • CRISPR/CAS9 technology expertise
  • Concept, design and “à la carte” preclinical models
  • PDX collection (T-ALL)