Ludovic Deriano
A5073033953- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Diabetes and associated disorders
- Genomics and Chromatin Dynamics
- Lymphoma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Genomic variations and chromosomal abnormalities
- Immune Response and Inflammation
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Cytomegalovirus and herpesvirus research
- Cancer therapeutics and mechanisms
- Carcinogens and Genotoxicity Assessment
- RNA and protein synthesis mechanisms
- COVID-19 Clinical Research Studies
- Circular RNAs in diseases
Institut Pasteur
2014-2024
Immunité et Cancer
2017-2024
Université Paris Cité
2022-2024
Inserm
2005-2024
École Polytechnique Fédérale de Lausanne
2022
Department of Genomes & Genetics
2016-2020
Centre National de la Recherche Scientifique
2005-2016
University of Cambridge
2016
Centre de Gestion Scientifique
2014
New York University
2007-2013
Significance Identifying the drivers of interindividual diversity human immune system is crucial to understand their consequences on immune-mediated diseases. By examining transcriptional responses 1,000 individuals various microbial challenges, we show that age and sex influence expression many immune-related genes, but effects are overall moderate, whereas genetic factors affect a smaller gene set with stronger effect. We identify numerous variants variation infection, which associated...
Abstract Individuals differ widely in their immune responses, with age, sex and genetic factors having major roles this inherent variability 1–6 . However, the variables that drive such differences cytokine secretion—a crucial component of host response to challenges—remain poorly defined. Here we investigated 136 identified smoking, cytomegalovirus latent infection body mass index as contributors response, effects comparable magnitudes genetics. We find smoking influences both innate...
Abstract Induced pluripotent stem cells (iPSCs) have considerably impacted human developmental biology and regenerative medicine, notably because they circumvent the use of embryonic origin offer potential to generate patient-specific cells. However, conventional reprogramming protocols produce developmentally advanced, or primed, iPSCs (hiPSCs), restricting their post-implantation development modeling. Hence, there is a need for hiPSCs resembling preimplantation naive epiblast. Here, we...
Tumors develop under the selective pressure of immune system. However, it remains critical to establish how system affects clonal heterogeneity tumors that often display cell-to-cell variation in genetic alterations and antigenic expression. To address these questions, we introduced a multicolor barcoding strategy study growth MYC-driven B cell lymphoma harboring large degree intratumor diversity. Using intravital imaging, visualized subclones grow as patches sessile cells bone marrow,...
Systems approaches for the study of immune signaling pathways have been traditionally based on purified cells or cultured lines. However, in vivo responses involve coordinated action multiple cell types, which interact to establish an inflammatory microenvironment. We employed standardized whole-blood stimulation systems test hypothesis that Toll-like receptor ligands whole microbes can be defined by transcriptional signatures key cytokines. found 44 genes, identified using Support Vector...
Epigenetic changes are required for normal development, yet the nature and respective contribution of factors that drive epigenetic variation in humans remain to be fully characterized. Here, we assessed how blood DNA methylome 884 adults is affected by sequence variation, age, sex 139 relating life habits immunity. Furthermore, investigated whether these effects mediated or not cellular composition, measured deep immunophenotyping. We show methylation differs substantially between naïve...
PAXX was identified recently as a novel nonhomologous end-joining DNA repair factor in human cells. To characterize its physiological roles, we generated Paxx -deficient mice. Like Xlf −/− mice, mice are viable, grow normally, and fertile but show mild radiosensitivity. Strikingly, while loss is epistatic with Ku80 , Lig4 Atm deficiency, Paxx/Xlf double-knockout display embryonic lethality associated genomic instability, cell death the central nervous system, an almost complete block...
The Milieu Intérieur Consortium has established a 1000-person healthy population-based study (stratified according to sex and age), creating an unparalleled opportunity for assessing the determinants of human immunologic variance. Herein, we define criteria utilized participant enrollment, highlight key data that were collected correlative studies. In this report, analyzed biological correlates sex, age, smoking-habits, metabolic score CMV infection. We characterized identified unique risk...
Paralog of XRCC4 and XLF (PAXX) is a member the superfamily plays role in nonhomologous end-joining (NHEJ), DNA repair pathway critical for lymphocyte antigen receptor gene assembly. Here, we find that functions PAXX V(D)J recombination are masked by redundant joining activities. Thus, combined deficiency leads to an inability join RAG-cleaved ends. Additionally, demonstrate function depends on its interaction with Ku. Importantly, show that, unlike XLF, during breaks does not overlap ATM...
Abstract XRCC4-like factor (XLF) functions in classical non-homologous end-joining (cNHEJ) but is dispensable for the repair of DNA double-strand breaks (DSBs) generated during V(D)J recombination. A long-standing hypothesis proposes that, addition to its canonical nuclease activity, RAG1/2 proteins participate phase Here we show that context RAG2 lacking C-terminus domain ( Rag2 c/c mice), XLF deficiency leads a profound lymphopenia associated with severe defect recombination and, absence...
Abstract The alternative non-homologous end-joining (NHEJ) pathway promotes DNA double-strand break (DSB) repair in cells deficient for NHEJ or homologous recombination, suggesting that it operates at all stages of the cell cycle. Here, we use an approach which breaks can be induced G1 and their tracked, enabling us to show joining DSBs is not functional G1-arrested XRCC4-deficient cells. Cell cycle entry into S-G2/M restores DSB by Pol θ-dependent PARP1-independent with products bearing...
MAD2L2 (REV7) plays an important role in DNA double-strand break repair. As a member of the shieldin complex, consisting MAD2L2, SHLD1, SHLD2 and SHLD3, it controls repair pathway choice by counteracting end-resection. Here we investigated requirements for complex assembly activity. Besides dimerization-surface, HORMA-domain protein has extraordinary ability to wrap its C-terminus around likely creating very stable complex. We show that appropriate function within requires dimerization,...
The DNA damage response (DDR) is an essential signaling pathway that detects lesions, which constantly occur upon either endogenous or exogenous assaults, and maintains genetic integrity. An infection by invading pathogen one such assault, but how bacteria impact the cellular DDR poorly documented. Here, we report with Listeria monocytogenes induces host breaks. Strikingly, signature to these breaks only moderately activated. We uncover role of listerial toxin listeriolysin O (LLO) in...
Abstract SHLD1 is part of the Shieldin (SHLD) complex, which acts downstream 53BP1 to counteract DNA double-strand break (DSB) end resection and promote repair via non-homologous end-joining (NHEJ). While essential for immunoglobulin heavy chain class switch recombination (CSR), long-range V(D)J RAG-induced DSBs in XLF-deficient cells, function SHLD during these processes remains elusive. Here we report that dispensable lymphocyte development RAG-mediated recombination, even absence XLF. By...