A5045195370- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Chronic Lymphocytic Leukemia Research
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Platelet Disorders and Treatments
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Erythrocyte Function and Pathophysiology
- RNA and protein synthesis mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Microtubule and mitosis dynamics
- RNA regulation and disease
- Cancer Cells and Metastasis
- interferon and immune responses
- Autoimmune Bullous Skin Diseases
- Bacterial Genetics and Biotechnology
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Research on Leishmaniasis Studies
Memorial Sloan Kettering Cancer Center
2020-2025
Kettering University
2023-2025
Inserm
2017-2024
Université Paris Cité
2024
Hôpital Saint-Louis
2024
Centre National de la Recherche Scientifique
2024
Assistance Publique – Hôpitaux de Paris
2024
Université Paris-Saclay
2022
Institut Gustave Roussy
2018-2022
New York Proton Center
2022
Highlights•GPATCH8 is required for mutant SF3B1-dependent splicing alterations•GPATCH8 involved in quality control of intronic branchpoint selection•GPATCH8 opposes activity SUGP1, and each competes interaction with DHX15•Deletion GPATCH8 corrects aberrant differentiation SF3B1-mutant MDS cellsSummaryMutations the RNA factor gene SF3B1 are common across hematologic solid cancers result widespread alterations splicing, yet there currently no therapeutic means to correct this mis-splicing....
Abstract Recently, screens for mediators of resistance to FLT3 and ABL kinase inhibitors in leukemia resulted the discovery LZTR1 as an adapter a Cullin-3 RING E3 ubiquitin ligase complex responsible degradation RAS GTPases. In parallel, dysregulated expression via aberrant splicing mutations was identified clonal hematopoietic conditions. Here we identify that loss LZTR1, or leukemia-associated mutants substrate GTPase RIT1 escape degradation, drives stem cell (HSC) expansion vivo. Although...
Abstract A major roadblock preventing durable responses to CD8+ T cell-based immunotherapies in melanoma and other solid cancers is loss or downregulation of human leukocyte antigen class I (HLA-I) on tumor cells. We hypothesized this immune escape mechanism might be overcome by tumor-reactive cytotoxic CD4+ cells which can directly engage that express HLA-II. Unlike HLA-I, the molecular mechanisms governing response resistance HLA-II presentation have previously not been studied a...
Super Enhancers (SEs) are clusters of regulatory elements associated with cell identity and disease. However, whether these induced by oncogenes can regulate gene modules cooperating for cancer transformation or maintenance remains elusive. To address this question, we conducted a genome-wide CRISPRi-based screening SEs in ETO2-GLIS2 + acute megakaryoblastic leukemia. This approach revealed essential leukemic growth survival that expression. In particular, identified de novo SE specific...
ABSTRACT Somatic mutations in cancer genes have been ubiquitously detected clonal expansions across healthy human tissue, including hematopoiesis. However, mutated and wildtype cells are morphologically phenotypically similar, limiting the ability to link genotypes with cellular phenotypes. To overcome this limitation, we leveraged multi-modality single-cell sequencing, capturing mutation transcriptomes methylomes stem progenitors from individuals DNMT3A R882 resulted myeloid over lymphoid...
Gene profiling studies have indicated that in vitro differentiated human megakaryocytes express the receptor for IL-21 (IL-21R), an immunostimulatory cytokine associated with inflammatory disorders and currently under evaluation cancer therapy. The aim of this study was to investigate whether modulates megakaryopoiesis. We first checked expression on bone marrow megakaryocytes. then investigated effect differentiation blood CD34+ progenitors into Finally, we analyzed consequences...
Abstract Recent advancements in shRNA and Cas protein technologies have enabled functional screening methods targeting genes or non-coding regions using single pooled sgRNA. CRISPR-based systems also been developed for modulating DNA accessibility, resulting CRISPR-mediated interference (CRISPRi) activation (CRISPRa) of targeted genomic elements. However, there is still a lack software tools integrating diverse array genomics outputs that could offer cohesive framework comprehensive data...
<div>Abstract<p>Recently, screens for mediators of resistance to FLT3 and ABL kinase inhibitors in leukemia resulted the discovery LZTR1 as an adapter a Cullin-3 RING E3 ubiquitin ligase complex responsible degradation RAS GTPases. In parallel, dysregulated expression via aberrant splicing mutations was identified clonal hematopoietic conditions. Here we identify that loss LZTR1, or leukemia-associated mutants substrate GTPase RIT1 escape degradation, drives stem cell (HSC)...
<div>Abstract<p>Recently, screens for mediators of resistance to FLT3 and ABL kinase inhibitors in leukemia resulted the discovery LZTR1 as an adapter a Cullin-3 RING E3 ubiquitin ligase complex responsible degradation RAS GTPases. In parallel, dysregulated expression via aberrant splicing mutations was identified clonal hematopoietic conditions. Here we identify that loss LZTR1, or leukemia-associated mutants substrate GTPase RIT1 escape degradation, drives stem cell (HSC)...
Supplementary Figure from Impaired Proteolysis of Noncanonical RAS Proteins Drives Clonal Hematopoietic Transformation
Supplementary Figure from Impaired Proteolysis of Noncanonical RAS Proteins Drives Clonal Hematopoietic Transformation
Background: In the recent years, massively parallel sequencing approaches allowed identification of hundreds mutated genes in Leukemia. Although these data gave unprecedented amount information about mechanisms leukemia cell maintenance and/or progression, functional characterization that are key player regulating cancer development remain laborious. Analysis at single gene level often fails to identify or pathway collaborations leading transformation. Studies aimed depicting new oncogene...
In the recent years, massively parallel sequencing approaches identified hundreds of mutated genes in cancer( 1 ) providing an unprecedented amount information about mechanisms cancer cell maintenance and progression. However, while (it is widely accepted that) transformation processes result from oncogenic cooperation between deregulated pathways, functional characterization candidate key players mostly performed at single gene level which generally inadequate to identify these oncogene...