IN VITRO AND IN VIVO MODELS FOR STUDYING THE FUNCTIONAL GENETICS OF ACUTE MYELOID LEUKEMIA IN CHILDREN
- Preclinical development
- AML
- Targeted therapy
- Preclinical research (TRL 4-5)
In vitro and in vivo studies of the molecular mechanisms involved in pediatric acute myeloid leukemia (AML).
We are developing in vitro and in vivo functional study models to address the molecular basis of pediatric acute myeloid leukemia. Our genetic and epigenetic analyses aim to better understand the activity of transcription factors and the influence of extrinsic factors on tumor development, leading to new therapeutic strategies.
Description
Scope of research activities
Preclinical research using in vitro and in vivo models for the development of new targeted therapies for pediatric AML:
- Molecular target validation
- Evaluation of drug candidate efficacy
Conduct of studies
Steps :
- Analysis of innovative product development strategy
- Study design
- Drafting of study plans
- Organization, implementation and conduct of studies
- Analysis and communication of results
Research infrastructure
Experimental and analytical platforms:
- Preclinical research platform (hosting preclinical cancer models; preclinical evaluation of models and therapies, phenotyping, experimental pathology)
- Integrated biology platform (genomics, proteomics and metabolomics)
- Imaging and cytometry platform
- Individual CRISPR/Cas9 screening or screens
- Bioinformatics (transcriptome, single cell transcriptome, chromatin accessibility, activity inference)
Models:
- AML PDX models
- Transgenic mouse models: doxycycline-inducible model of ETO2-GLIS2 fusion expression in a C57BL/6 background
- Leukemia cell lines: MO7e, CMS, CMK, HEL, lines with oncogenes expressing a fluorescent tag (GFP or Scarlet) or a degron
- Human induced pluripotent stem (iPSC) cell lines expressing oncogenes
Technical personnel:
- Pre-clinical experimentation technician/engineer
Specifications
The platform
Preclinical analysis of the efficacy of new molecules on leukemic development. Genetic analysis and functional characterization of molecular abnormalities in childhood AML.
Studies
Transcriptomic/epigenetic studies:
- Gene expression at population or single-cell level
- Access to chromatin (ATAC-seq)
Protein-protein interaction studies:
- Co-immunoprecipitation
Molecular engineering (CRISPR/Cas9 approach):
- Gene inactivation
- Screening using inactivation libraries of different sizes
Visualization of leukemic progression in preclinical models:
- Latency
- Phenotype (flow cytometry)
Examples of partnerships
Targeting aggressive AML - Testing the formulation of liposomes loaded with apoptosis inhibitors.
Partner: Université Paris-Saclay
Terms
OPALE entity
Gustave Roussy (UMR-1170)
Team leader
Contact
Dr. Sandrine PalcyBusiness Development Director