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- Normal and pathological hematopoiesis
- Niche, Cancer, and Radiation in Hematopoiesis
- Population Evolution and Interaction Particle Systems
- Translational Immunology in Immunotherapy and Hematology (TIGITH)
- Identification and targeting of extrinsic regulators of myeloid malignancies
- Lymphoid niches, Chemokines and Immuno-hematological syndromes
- Molecular Mechanisms of Acute Myeloid Leukemia Development
- Chronic Myeloid Malignancies, Microenvironment & Translational Research
- Leukemia & Niche Dynamics
- Genetic and Epigenetic control of Normal and Malignant Hematopoiesis
- Stem cell dysfunction and secondary AML
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Accueil Genetic and Epigenetic control of Normal and Malignant HematopoiesisGenetic and Epigenetic control of Normal and Malignant Hematopoiesis
...Camille Lobry
Team leader
Research themes
AML is the most common acute leukemia diagnosed in adults and has a dismal overall survival with few targeted therapies. Non-coding regions in the genome play an important role in regulating gene transcription and encompass insulators, enhancers and non-coding RNA. Study of these regions could help decipher leukemogenic mechanisms and help design novel targeted therapies.
- AML : Acute Myeloid Leukemia
- sAML : Secondary Acute Myeloid Leukemia
- MDS : Myelodysplastic Syndromes
Research areas
Super Enhancers (SE) have been characterized as single or group of enhancers with unusual strong enrichment for binding of transcriptional co-activators and strong modifications of histone tails. Leukemic cells often present with altered gene expression patterns and enhancer usage compared to their normal counterparts. SE tend to be enriched around and control genes known to play oncogenic functions. Our results show that SE profiles and activity are depending on oncogenic lesions and particularly that fusion oncogenes can hijack genomic regions to create aberrant de novo SE inducing oncogenes upregulation. We use combinations of genome wide transcriptomic and epigenomic approaches together with high throughput screening technologies based on CRISPR/Cas9, shRNA and CRISPRi to interrogate SE functions and their importance in transcription regulation and leukemia progression.
Essential oncogenes and oncogenics programs, such as MYC, control metabolic gene expression in leukemic cells and induce metabolic shift or reprogramming during transformation and progression of the disease. Conversely, several epigenetic regulators depend on metabolic intermediates to perform their catalytic functions and metabolic dysregulations impact on gene expression programs in leukemic cells. Understanding this interplay could help identify novel vulnerabilities in leukemic cells. In collaboration with Puissant Lab we deploy state of the art in vivo and in vitro models combined with multi-omic characterizations to explore and decipher these intricate mechanisms.
With the advent of massively parallel sequencing and development of many multi-omics techniques, cancer research relies more and more on state of the art molecular biology and bionformatics analyses not easily accessible to regular biologists. Our team helps researcher design and perform classical omics techniques such as RNA-seq, scRNA-seq, ChIP-seq, ATAC-seq and high throughput screening using CRISPR/Cas9 or shRNA and designs standardized bioinformatics analysis pipelines to help researchers explore their data.
Team members
Camille LobryResearch Director, Team LeaderSéverine LecourtResearch EngineerIsmail El-AzrakAssistant EngineerNaelle GuillonBioinformatics EngineerPaul-Arthur MeslinPhD Student in BioinformaticsChloé ZédouardPhD Student (Joint Supervision with Puissant Lab)Rayan DaherApprentice, M2 BioinformaticsRanya AlawadhiM2 StudentScientific publications
PitViper: a software for comparative meta-analysis and annotation of functional screening data
Paul-Arthur Meslin & al, NAR Genomics and Bioinformatics, 2024Lire la publicationThe Folate Cycle Enzyme MTHFR Is a Critical Regulator of Cell Response to MYC-Targeting Therapies
Angela Su & al, Cancer Discov, 2020Lire la publicationScreening of ETO2-GLIS2-induced Super Enhancers identifies targetable cooperative dependencies in acute megakaryoblastic leukemia
Salima Benbarche & al, Science Adv, 2022Lire la publicationFunding
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