A5054788344- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cellular transport and secretion
- Cellular Mechanics and Interactions
- Plant Reproductive Biology
- Viral gastroenteritis research and epidemiology
- CRISPR and Genetic Engineering
- RNA regulation and disease
- Evolution and Science Education
- Evolutionary Psychology and Human Behavior
- Genetic and rare skin diseases.
- Reproductive tract infections research
- Bacteriophages and microbial interactions
- Gut microbiota and health
- Chromosomal and Genetic Variations
- Animal Virus Infections Studies
- Cytomegalovirus and herpesvirus research
- Transgenic Plants and Applications
- Immunodeficiency and Autoimmune Disorders
- DNA Repair Mechanisms
- Enzyme Structure and Function
University of Chicago
2013-2024
Yale University
2016-2021
Laboratoire d'Enzymologie et Biochimie Structurales
2011
Centre National de la Recherche Scientifique
2011
V(D)J recombination assembles and diversifies Ig T cell receptor genes in developing B lymphocytes. The reaction is initiated by the RAG1-RAG2 protein complex which binds cleaves at discrete gene segments antigen loci. To identify mechanisms that regulate recombination, we used proximity-dependent biotin identification to analyze interactomes of full-length truncated forms RAG1 pre-B cells. This revealed an association with numerous nucleolar proteins a manner dependent on amino acids 216...
The Scar/Wave complex (SWC) generates lamellipodia through Arp2/3-dependent polymerisation of branched actin networks. In order to identify new SWC regulators, we conducted a screen in Drosophila cells combining proteomics with functional genomics. This identified Clathrin heavy chain (CHC) as protein that binds the and whose depletion affects lamellipodium formation. role CHC formation can be uncoupled from its membrane trafficking by several experimental approaches. Furthermore, is...
Immunoglobulin and T cell receptor gene assembly depends on V(D)J recombination initiated by the RAG1-RAG2 recombinase. The RAG1 N-terminal region (NTR; aa 1–383) has been implicated in regulatory functions whose influence lymphocyte development vivo is poorly understood. We generated mice which lacks ubiquitin ligase activity (P326G), major site of autoubiquitination (K233R), or its first 215 residues (Δ215). While few abnormalities were detected R1.K233R mice, R1.P326G exhibit multiple...
A whole-genome CRISPR/Cas9 screen identified ATP2A2, the gene encoding Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2 protein, as being important for V(D)J recombination. SERCAs are ER transmembrane proteins that pump Ca2+ from cytosol into lumen to maintain reservoir and regulate cytosolic Ca2+-dependent processes. In preB cells, loss of SERCA2 leads reduced recombination kinetics due diminished RAG-mediated DNA cleavage. deficiency in B cells increased expression SERCA3, combined SERCA3...
ABSTRACT Commensal microbes are often required to control viral infection by facilitating host immune defenses. However, we found that this does not hold true for retroviral infection. We report retrovirus-resistant mice the pathogen with virus-neutralizing antibodies independently of commensal microbiota. This is in contrast orthomyxoviruses and arenaviruses, where resistance ablated animals depleted Clearly, when it comes antiviral immunity, role microbiota cannot be generalized.
The vast diversity of mammalian adaptive antigen receptors allows for robust and efficient immune responses against a wide number pathogens. receptor repertoire is built during the recombination B T cell (BCR, TCR) loci hypermutation BCR loci. V(D)J rearranges these loci, which are organized as an array separate V, (D), J gene segments. Transcription activation at recombining locus leads to changes in local three-dimensional architecture, subsequently contributes segments utilized...
Viruses, including retroviruses, can be passed from mothers to their progeny during birth and breastfeeding. It is assumed that newborns may develop immune tolerance milk-transmitted pathogens similarly food antigens. I/LnJ mice are uniquely resistant retroviruses acquired as or adults they produce virus-neutralizing antibodies (Abs). A loss-of-function allele of H2-Ob (Ob), originally mapped within the virus infectivity controller 1 (vic1) locus, responsible for production antiretrovirus...
Abstract The vast diversity of mammalian adaptive antigen receptors allows for robust and efficient immune responses against a wide number pathogens. receptor repertoire is built during the recombination hypermutation B T cell (BCR, TCR) loci. V(D)J rearranges these loci, which are organized as an array separate V, (D), J gene segments. Transcription activation at recombining locus leads to changes in local three-dimensional architecture, subsequently contributes segments utilized...
The Scar/Wave complex (SWC) generates lamellipodia through Arp2/3-dependent polymerisation of branched actin networks. In order to identify new SWC regulators, we conducted a screen in Drosophila cells combining proteomics with functional genomics. This identified Clathrin heavy chain (CHC) as protein that binds the and whose depletion affects lamellipodium formation. role CHC formation can be uncoupled from its membrane trafficking by several experimental approaches. Furthermore, is...
ABSTRACT Differential responses to viral infections are influenced by the genetic makeup of host. Studies resistance retroviruses in human populations complicated due inability conduct proof-of-principle studies. Inbred mouse lines, which have a range susceptible phenotypes retroviruses, an ideal tool identify and characterize mechanisms define their underpinnings. YBR/Ei mice become infected with Mouse Mammary Tumor Virus, mucosally transmitted murine retrovirus, but eliminate virus from...