Genetic and Epigenetic control of Normal and Malignant Hematopoiesis

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Camille Lobry

Team leader

Stéphanie CHAMBAUD

Research themes

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 Lobry
Research Director, Team Leader
Séverine Lecourt
Research Engineer
Ismail El-Azrak
Assistant Engineer
Naelle Guillon
Bioinformatics Engineer
Paul-Arthur Meslin
PhD Student in Bioinformatics
Chloé Zédouard
PhD Student (Joint Supervision with Puissant Lab)
Rayan Daher
Apprentice, M2 Bioinformatics
Ranya Alawadhi
M2 Student

Scientific publications

PitViper: a software for comparative meta-analysis and annotation of functional screening data

PitViper: a software for comparative meta-analysis and annotation of functional screening data

Paul-Arthur Meslin & al, NAR Genomics and Bioinformatics, 2024
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The Folate Cycle Enzyme MTHFR Is a Critical Regulator of Cell Response to MYC-Targeting Therapies

The Folate Cycle Enzyme MTHFR Is a Critical Regulator of Cell Response to MYC-Targeting Therapies

Angela Su & al, Cancer Discov, 2020
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Screening of ETO2-GLIS2-induced Super Enhancers identifies targetable cooperative dependencies in acute megakaryoblastic leukemia

Screening of ETO2-GLIS2-induced Super Enhancers identifies targetable cooperative dependencies in acute megakaryoblastic leukemia

Salima Benbarche & al, Science Adv, 2022
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Funding

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