- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Chromosomal and Genetic Variations
- Plant Molecular Biology Research
- Single-cell and spatial transcriptomics
- Diabetes and associated disorders
- RNA Research and Splicing
- CAR-T cell therapy research
- Chromatin Remodeling and Cancer
- Cancer Genomics and Diagnostics
- RNA Interference and Gene Delivery
University of Chicago
2018-2022
Yale University
2014
Among tetrapods, only urodele salamanders, such as the axolotl Ambystoma mexicanum, can completely regenerate limbs adults. The mystery of why but not other animals, possess this ability has for generations captivated scientists seeking to induce phenomenon in vertebrates. Although many recent advances molecular biology have allowed limb regeneration and tissue repair be investigated increasing detail, toolkit study process been limited. Here, we report that CRISPR-Cas9 RNA-guided nuclease...
Immunoreceptor gene recombination requires complementary 12 bp and 23 signal sequences (RSSs). In addition, the RSSs that assemble RAG proteins, centers, must be accessible yet flanked by a 5-prime nucleosome decorated with H3K4me3. Drosophila, DNA GAGA motifs play an important role in positioning. Herein, we report to each functional Jk RSS is motif conserved across mammalian species. mice, Jk1 regulated local accessibility placement. Furthermore, it was required for Vk-Jk1 recombination....
Abstract Transcription factor (TF) networks determine cell fate in hematopoiesis. However, how TFs cooperate with other regulatory mechanisms to instruct transcription remains poorly understood. Here we show that small pre-B cells, the lineage restricted epigenetic reader BRWD1 closes early development enhancers and opens of late B lymphopoiesis TF binding. regulates over 7000 genes repress proliferative induce differentiation programs. does not regulate expression required for...
Expression of vast repertoires antigen receptors by lymphocytes, with each cell expressing a single receptor, requires stochastic activation individual variable (V) genes for transcription and recombination. How this occurs remains unknown. Using single-cell RNA sequencing (scRNA-seq) allelic variation, we show that pre-B cells monoallelically transcribe divergent arrays Vκ genes, thereby opening subsequent Vκ-Jκ Transcription upon translocation to polymerase II arrayed on the nuclear matrix...
During B lymphopoiesis, cell progenitors progress through alternating and mutually exclusive stages of clonal expansion immunoglobulin (Ig) gene rearrangements. Great diversity is generated the stochastic recombination Ig segments encoding heavy light chain variable domains. However, this commonly generates autoreactivity. Receptor editing predominant tolerance mechanism for self-reactive cells in bone marrow (BM). receptor rescues autoreactive from negative selection renewed first at