A5074026984- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Immunodeficiency and Autoimmune Disorders
- Acute Lymphoblastic Leukemia research
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Immune Response and Inflammation
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Single-cell and spatial transcriptomics
- Gene Regulatory Network Analysis
- SARS-CoV-2 detection and testing
- RNA modifications and cancer
- Genetic Syndromes and Imprinting
- Gut microbiota and health
- Genetics and Neurodevelopmental Disorders
- Animal Genetics and Reproduction
- Innovation and Socioeconomic Development
- Pneumocystis jirovecii pneumonia detection and treatment
Universidade Nova de Lisboa
2019-2022
University of Lisbon
2021
Nova Medical (United States)
2021
Instituto Politécnico de Lisboa
2021
Instituto Gulbenkian de Ciência
2001-2016
Rockefeller University
2003-2010
Center of Molecular Immunology (Cuba)
2004-2006
Howard Hughes Medical Institute
2004
Institut Pasteur
2000-2001
Centre National de la Recherche Scientifique
2001
Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated in activated B lymphocytes by activation-induced deaminase (AID). AID is thought to make lesions DNA deaminating cytidine residues single-stranded exposed RNA polymerase during transcription. Although this must occur the nucleus, found primarily cytoplasm. Here we show that actively excluded from nucleus an exportin CRM1-dependent pathway. The nuclear export signal (NES) at carboxyl terminus of a region overlaps...
Activation-induced cytidine deaminase (AID) initiates Ig class switch recombination and somatic hypermutation by producing U:G mismatches in DNA. These also have the potential to induce DNA damage including double-stranded breaks chromosome translocations; therefore, strict regulation of AID is important for maintaining genomic stability. In addition transcriptional regulation, it has been proposed that phosphorylation can modulate activity. Using a combination MS immunochemical approaches...
Class switch recombination was the last of lymphocyte-specific DNA modification reactions to appear in evolution adaptive immune system. It is absent cartilaginous and bony fish, it common all tetrapods. switching initiated by activation-induced cytidine deaminase (AID), an enzyme expressed fish that also required for somatic hypermutation. Fish AID differs from orthologs found tetrapods several respects, including its catalytic domain carboxy-terminal region, both which are essential...
Dendritic cells (DCs) are phagocytes that highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) spleen, which is major site control blood-borne infections such as malaria. However, dynamics splenic during Plasmodium poorly understood, limiting our knowledge regarding their protective role in Here, we used vivo experimental approaches enabled us to deplete or visualize order clarify these issues. To...
Abstract Interleukin-7 receptor α (encoded by IL7R ) is essential for lymphoid development. Whether acute lymphoblastic leukemia (ALL)-related gain-of-function mutations can trigger leukemogenesis remains unclear. Here, we demonstrate that lymphoid-restricted mutant , expressed at physiological levels in conditional knock-in mice, establishes a pre-leukemic stage which B-cell precursors display self-renewal ability, initiating resembling PAX5 P80R or Ph-like human B-ALL. Full transformation...
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric cancer. Amongst the wide array of driver mutations, 10% T-ALL patients display gain-of-function mutations in IL-7 receptor α chain (IL-7Rα, encoded by IL7R), which occur different molecular subtypes this disease. However, it still unclear whether IL-7R mutational activation sufficient to transform precursors. Also, genes cooperate with IL7R drive leukemogenesis remain poorly defined. Here, we demonstrate that mutant alone...
Abstract Ig H chain (IgH) allelic exclusion remains a puzzling topic. Here, we address the following question: Do phenotypic IgH allelically included cells exist in normal mice and, if so, at what frequency? Sorted from heterozygous were evaluated for expression of both IgM allotypes by double intracytoplasmic stainings. Dual expressors found frequency 1 104 splenic B cells. These data confirmed direct sequencing IgH-rearranged alleles obtained after single cell (or clone) PCR on dual...
Recombination-Activating Genes (RAG) 1 and 2 form the site specific recombinase that mediates V(D)J recombination, a process of DNA editing required for lymphocyte development responsible their diverse repertoire antigen receptors. Mistargeted RAG activity associates with genome alteration is various lymphoid tumors. Moreover several non-lymphoid tumors express ectopically. A practical powerful tool to perform quantitative assessment score putative RAG-Recognition signal sequences (RSS) in...
Abstract How the vast majority of B cells express only one two alleles at their immunoglobulin loci remains a biological puzzle. Here, in mice reconstituted with single haematopoietic stem cell, we demonstrate that each heavy chain ( Igh ) has similar probability to be first undergo V H DJ rearrangement. We also observe this clones from multipotent and common lymphoid precursors. The extreme biases expression find more differentiated subsets are mostly due constraints imposed by early...
The recombination activating proteins (RAG1 and RAG2) are essential for V(D)J of immunoglobulin chains. Expression both genes is lymphocyte-specific RAG levels tightlyregulated throughout lymphopoiesis cell cycle. To assess the significance this pattern expression, we generated transgenic mice expressing Rag continuously lymphocyte development constitutively in most non-lymphoid tissues. transgenes partially complement an endogenous Rag2 null mutation lead to a partial block early B T when...
Activation-induced cytidine deaminase (AID) is a DNA editing protein that plays an essential role in three major events of immunoglobulin (Ig) diversification: somatic hypermutation, class switch recombination and Ig gene conversion. Mutations the AID (AICDA) have been found patients with autosomal recessive Hyper-IgM (HIGM) syndrome type 2. Here, two 9- 14-year-old Brazilian sisters, from consanguineous family, were diagnosed HIGM2 syndrome. Sequencing analysis exons AICDA revealed both are...
The RAG recombinase is a domesticated transposable element co-opted in jawed vertebrates to drive the process of so-called V(D)J recombination, which hallmark adaptive immune system produce antigen receptors. targets, namely, Recombination Signal Sequences (RSS), are rather long and degenerated sequences, highlights ability interact with wide range target including outside receptor loci. recognition such cryptic targets by threatens genome integrity promoting aberrant DNA as observed...
Background Adults are being vaccinated against SARS-CoV-2 worldwide, but the longitudinal protection of these vaccines is uncertain, given ongoing appearance variants. Children remain largely unvaccinated and susceptible to infection, with studies reporting that they actively transmit virus even when asymptomatic, thus affecting community. Methods We investigated if saliva an effective sample for detecting RNA antibodies in children, associated viral levels infectivity. For that, we used a...
Phenotypic variation in the copy number of gene products expressed by cells or tissues has been focus intense investigation. To what extent observed differences cellular expression levels are persistent transient is an intriguing question. Here, we develop a quantitative framework that resolves into stable and unstable components. The difference between means two cohorts isolated from any cell population shown to converge asymptotic value, with characteristic time, τT, measures timescale...
V(H)DJ(H) recombination has been extensively studied in mice carrying an Ig heavy chain rearranged transgene. In most models, inhibition of endogenous rearrangement occurs, consistently with the feedback model IgH recombination. Nonetheless, incomplete allelic exclusion is a recurrent observation these animals. Furthermore, transgene expression ontogeny likely to start before somatic recombination, thus limiting use Ig-transgenic access dynamics As alternative approach, we challenged...