A5038977410- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- SARS-CoV-2 and COVID-19 Research
- Cancer-related gene regulation
- Viral Infectious Diseases and Gene Expression in Insects
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- SARS-CoV-2 detection and testing
- Monoclonal and Polyclonal Antibodies Research
- Genetics, Aging, and Longevity in Model Organisms
- Reproductive Biology and Fertility
- Sex and Gender in Healthcare
- Fibroblast Growth Factor Research
- Stress Responses and Cortisol
- Eosinophilic Esophagitis
- Spine and Intervertebral Disc Pathology
- IL-33, ST2, and ILC Pathways
- Hippo pathway signaling and YAP/TAZ
- Microfluidic and Bio-sensing Technologies
- Herpesvirus Infections and Treatments
- Immunodeficiency and Autoimmune Disorders
Center for Excellence in Molecular Cell Science
2013-2024
Yale University
2022-2024
Chinese Academy of Sciences
2013-2024
Center for Systems Biology
2022-2023
Yale New Haven Health System
2023
Yale Cancer Center
2023
University of Chinese Academy of Sciences
2018-2022
Shanghai Institutes for Biological Sciences
2013-2016
ShanghaiTech University
2013-2016
Highlights•A dominant cataract-causing mutation in the Crygc gene is corrected using CRISPR-Cas9•Genetic correction via HDR uses information from endogenous WT allele•Genetic can also occur an exogenous oligo•The rescued mice transmit allele to their progenySummaryThe CRISPR-Cas9 system has been employed generate mutant alleles a range of different organisms. However, so far there have not reports use this for efficient genetic disease. Here we show that with causes cataracts could be by...
Epigenetic regulation, including histone-to-protamine exchanges, controls spermiogenesis. However, the underlying mechanisms of this regulation are largely unknown. Here, we report that PHF7, a testis-specific PHD and RING finger domain-containing protein, is essential for exchange in mice. PHF7 specifically expressed during deletion results male infertility due to aberrant histone retention impaired protamine replacement elongated spermatids. Mechanistically, can simultaneously bind H2A H3;...
Abstract Immune evasion is a critical step of cancer progression that remains major obstacle for current T cell–based immunotherapies. Hence, we investigated whether it possible to genetically reprogram cells exploit common tumor-intrinsic mechanism whereby suppress T-cell function by generating metabolically unfavorable tumor microenvironment (TME). In an in silico screen, identified ADA and PDK1 as metabolic regulators. We then showed overexpression (OE) these genes enhanced the cytolysis...
Abstract Activation-induced cytidine deaminase (AID) mediates class switching by binding to a small fraction of single-stranded DNA (ssDNA) diversify the antibody repertoire. The precise mechanism for highly selective AID targeting in genome has remained elusive. Here, we report an RNA-binding protein, ROD1 (also known as PTBP3 ), that is both required and sufficient define AID-binding sites genome-wide activated B cells. interacts with via ultraconserved loop, which proves be critical...
Group 2 innate lymphoid cells (ILC2s) manifest tissue heterogeneity and are crucial modulators of regional immune responses. The molecular mechanisms regulating ILC2 properties remain elusive. Here, we interrogate the signatures ILC2s from five tissues at transcriptome epigenetic level. We have found that microenvironment strongly shapes identities. intestine induces Aiolos+ILC2s, whereas lung pancreas enhance Galectin-1+ILC2s. Though being a faithful gut feature under steady state, Aiolos...
The Pi9 gene, an element belonging to Nucleotide-Binding Site Leucine-Rich Repeat (NBS-LRR) family, a positive regulator and critical in plant defence mechanism against blast fungus millets & rice. Despite the fact that NBS-LRR genes are found across various species, including millets, no studies have specifically investigated gene Eleusine coracana genome can be used effectively combat disease causing up 80% yield loss. Upon infection, pathogen secretes Avr protein into host cell, where...
Mutagenic screening is powerful for identifying key genes involved in developmental processes. However, such screens are successful only lower organisms. Here, we develop a targeted genetic approach mice through combining androgenetic haploid embryonic stem cells (AG-haESCs) and clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 (CRISPR-Cas9) technology. We produced mutant semi-cloned (SC) pool by oocyte injection of AG-haESCs carrying constitutively expressed...
The congenital intellectual disability (ID)-causing gene mutations remain largely unclear, although many genetic variations might relate to ID. We screened in Chinese Han children suffering from severe ID and found a single-nucleotide polymorphism (SNP) the 5′-untranslated region (5′-UTR) of fibroblast growth factor 13 (FGF13) mRNA (NM_001139500.1:c.-32c>G) shared by three male children. In both HEK293 cells patient-derived induced pluripotent stem cells, this SNP reduced translation...
Heparan sulfate proteoglycan 2 (HSPG2) gene encodes the matrix protein Perlecan, and genetic inactivation of this creates mice that are embryonic lethal with severe neural tube defects (NTDs). We discovered rare variants HSPG2 in 10% cases compared to only 4% controls among a cohort 369 NTDs. Endorepellin, peptide cleaved from domain V is known promote angiogenesis autophagy endothelial cells. The roles enderepellin neurodevelopment remain unclear so far. Our study revealed endorepellin can...
Loss of chondroitin sulfate (CS) has been reported to play a key role during intervertebral disc degeneration (IDD). However, the detailed mechanism CS and its synthases have not elucidated. Since is mainly synthesized by 3 (Chsy3), here, Chsy3 knockout mice are generated using CRISPR-Cas9 semi-cloning technology study IDD. We find that expression decreased IDD both in human nucleus pulposus (NP) tissue, shows spontaneous phenotype resembles samples Chsy3−/− mice. Taking advantage RNA-Seq...
Natural killer (NK) cells are an innate immune cell type that serves at the first level of defense against pathogens and cancer. NK have clinical potential, however, multiple current limitations exist naturally hinder successful implementation therapy cancer, including their effector function, persistence, tumor infiltration. To unbiasedly reveal functional genetic landscape underlying critical characteristics we perform perturbomics mapping infiltrating by joint in vivo AAV-CRISPR screens...
Alternative polyadenylation (APA) is a critical post-transcriptional process that generates mRNA isoforms with distinct 3' untranslated regions (3' UTRs), thereby regulating localization, stability, and translational efficiency. Cell-type-specific APA extensively shapes the diversity of cellular transcriptome, particularly during cell fate transition. Despite its recognized significance, precise regulatory mechanisms governing cell-type-specific remain unclear. In this study, we uncover...
Chimeric antigen receptor (CAR) T cells are powerful therapeutics; however, their efficacy is often hindered by critical hurdles. Here, utilizing the endocytic feature of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) cytoplasmic tail (CT), we reprogram CAR function and substantially enhance CAR-T in vivo . with monomeric, duplex, or triplex CTLA-4 CTs (CCTs) fused to C-terminus exhibit a progressive increase cytotoxicity under repeated stimulation, accompanied reduced activation...
The SARS-CoV-2 variant, Omicron (B.1.1.529), rapidly swept the world since its emergence. Compared with previous variants, has a high number of mutations, especially those in spike glycoprotein that drastically dampen or abolish efficacy currently available vaccines and therapeutic antibodies. Several major sublineages evolved, including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3, BA.4/5, BA.2.75, which changing global regional landscape pandemic. Although are available, antibodies remain critical...