- T-cell and B-cell Immunology
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- COVID-19 Clinical Research Studies
- DNA Repair Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Renal and related cancers
- Immunotherapy and Immune Responses
- Genetic Syndromes and Imprinting
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- Animal Genetics and Reproduction
- CAR-T cell therapy research
- Bacteriophages and microbial interactions
- Viral Infections and Outbreaks Research
- Neurogenesis and neuroplasticity mechanisms
- Chromosomal and Genetic Variations
Harvard University
2018-2023
Boston Children's Hospital
2018-2023
Center for Excellence in Molecular Cell Science
2014-2023
Boston Children's Museum
2023
Howard Hughes Medical Institute
2018-2022
University of Chinese Academy of Sciences
2022
Shanghai Institutes for Biological Sciences
2014-2016
Chinese Academy of Sciences
2014-2016
SARS-CoV-2 Omicron subvariants have generated a worldwide health crisis due to resistance most approved neutralizing antibodies and evasion of vaccination-induced antibodies. To manage prepare for new ones, additional means isolating broad potent humanized are desirable. Here, we describe mouse model in which the primary B cell receptor (BCR) repertoire is solely through V(D)J recombination human V H 1-2 heavy chain (HC) and, substantially, Vκ1-33 light (LC). Thus, BCR diversity these mice...
Abstract The Ten-eleven translocation (TET) family of dioxygenases mediate cytosine demethylation by catalyzing the oxidation 5-methylcytosine (5mC). TET-mediated DNA controls proper differentiation embryonic stem cells and TET members display functional redundancy during early gastrulation. However, it is unclear if proteins have significance in mammalian skeletal development. Here, we report that Tet genes deficiency mesoderm mesenchymal results severe defects bone existence any single...
Immunoglobulin heavy chain variable region exons are assembled in progenitor-B cells, from V
Abstract Immunoglobulin heavy chain locus ( Igh ) V H , D, and J gene segments are developmentally assembled into V(D)J exons. RAG endonuclease initiates recombination by binding a -recombination signal sequence (RSS) within chromatin-based center (RC) then, in an orientation-dependent process, scans upstream D-containing chromatin presented cohesin-mediated loop extrusion for convergent D-RSSs to initiate DJ -RC formation 1,2 . In primary pro-B cells, 100s of -associated RSSs, embedded...
Abstract SARS-CoV-2 Omicron variants have generated a world-wide health crisis due to resistance most approved neutralizing antibodies and evasion of induced by vaccination. Here, we describe the SP1-77 antibody that was from humanized mouse model with single human V H 1-2 Vκ1-33-associated immensely diverse complementarity-determining-region-3 (CDR3) sequences. potently broadly neutralizes concern binds spike protein receptor-binding-domain (RBD) via novel-CDR3-based mode. does not block...
We provide a protocol for neural blastocyst complementation \(NBC), method we have developed studying development and function of speci c forebrain regions.We describe all experimental steps from genetically modifying locus interest, via CRISPR/Cas9 editing in mouse embryonic stem cells \ (ESCs), to generating chimeric mice with ESC-reconstituted regions that can be directly analyzed.Our _in vivo_ brain organogenesis approach is e cient, allowing functional systematic analysis genes \(or...
ABSTRACT Immunoglobulin heavy chain variable region exons are assembled in progenitor-B cells, from V H , D, and J gene segments located separate clusters across the Igh locus. RAG endonuclease initiates V(D)J recombination a -based center (RC). Cohesin-mediated extrusion of upstream chromatin past RC-bound presents Ds for joining to s form DJ -RC. has provocative number organization CTCF-binding-elements (CBEs) that can impede loop extrusion. Thus, two divergently oriented CBEs (CBE1 CBE2)...