A5087193486- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- RNA Interference and Gene Delivery
- RNA regulation and disease
- Cancer-related Molecular Pathways
- CAR-T cell therapy research
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Ear Surgery and Otitis Media
- Cancer-related gene regulation
- Nuclear Structure and Function
- Genomics and Chromatin Dynamics
- Gene expression and cancer classification
- Obstructive Sleep Apnea Research
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- Phonocardiography and Auscultation Techniques
- Genetics, Aging, and Longevity in Model Organisms
- MicroRNA in disease regulation
- Mesenchymal stem cell research
- Pluripotent Stem Cells Research
- NF-κB Signaling Pathways
- Lipid metabolism and biosynthesis
- Cardiomyopathy and Myosin Studies
Hinge Health
2025
New York University
2020-2024
Cardiovascular Research Center
2024
Shenzhen University
2019-2021
Shanxi Medical University
2019
First Hospital of Shanxi Medical University
2019
Peking University
2015-2018
Jiangxi Pingxiang People's Hospital
2017
Ministry of Education of the People's Republic of China
2015
State Key Laboratory of Natural and Biomimetic Drugs
2015
β-Catenin, which is a key mediator of the wingless-integration site (Wnt)/β-catenin signaling pathway, plays an important role in cell proliferation, fate determination, and tumorigenesis, by regulating expression wide range target genes. Although variety posttranslational modifications are involved β-catenin activity, lysine methylation activity largely unknown. In this study, su(var)3-9, enhancer-of-zeste, trithorax (SET) domain-containing protein 7 (SET7/9), methyltransferase, interacted...
Significance The G9a histone methyltransferase primarily regulates the expression of genes associated with cancer development in cells, but it has also been implicated mediating DNA damage response. Here, we confirmed a role for repair following double-strand breaks. is recruited to chromatin as result casein kinase 2-mediated phosphorylation, where directly interacts replication protein A (RPA). binding RPA modulates and Rad51 foci formation permits efficient homologous recombination. This...
Linker histone H1 is a master regulator of higher order chromatin structure, but its involvement in the DNA damage response and repair unclear. Here, we report that linker H1.2 an essential ataxia telangiectasia mutated (ATM) activation. We show protects from aberrant ATM activation through direct interaction with HEAT repeat domain inhibition MRE11-RAD50-NBS1 (MRN) complex-dependent recruitment. Upon damage, undergoes rapid PARP1-dependent dissociation poly-ADP-ribosylation (PARylation) C...
Abstract Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and usually de novo mutation in the LMNA gene. Base editors (BEs) composed of cytidine deaminase fused to CRISPR/Cas9 nickase highly efficient at inducing C T base conversions programmable manner can be used generate animal disease models with amino-acid substitutions. Here, we generated first monkey model...
To solve the clinical transformation dilemma of lamin A/C (LMNA)-mutated dilated cardiomyopathy (LMD), we developed an LMNA-mutated primate model based on similarity between phenotype primates and humans. We screened out patients with LMD compared data TTN-mutated mutation-free to obtain unique phenotype. After establishment LMNA c.357-2A>G model, were continuously observed for 48 months, echocardiographic, electrophysiological, histologic, transcriptional recorded. The was found highly...
Background and Aim: DOT1L regulates various genes involved in cancer onset progression by catalyzing H3K79 methylation, but how activity itself is regulated unclear. Here, we aimed to identify specific post-translational modifications that might regulate thus impact on colorectal (CRC) progression. Methods: We conducted affinity purification mass spectrometry explore modifications. then established transwell migration invasion assays specifically investigate the role of DOT1L(K358)...
Abstract Genetically engineered T-cell therapies rely heavily on genome editing tools, such as the CRISPR/Cas9 system. However, unintended on-target chromosomal alterations, including large deletions and chromosome loss can occur pose significant risks tumorigenesis. Here we combined CasPlus optimized guide RNAs to reduce these issues in engineering human primary T cells. CasPlus, which integrates an T4 DNA polymerase with Cas9 nuclease RNA, promotes favorable small insertions (1-2 bp) while...
Abstract The binding of p53-binding protein 1 (53BP1) to damaged chromatin is a critical event in non-homologous DNA end joining (NHEJ)-mediated damage repair. Although several molecular pathways explaining how 53BP1 binds have been described, the precise underlying mechanisms are still unclear. Here we report that newly identified H4K16 monomethylation (H4K16me1) mark involved activity response (DDR). During DDR, H4K16me1 rapidly increases as result catalyzation by histone methyltransferase...
Ataxia telangiectasia and Rad3 related (ATR) activation after replication stress involves a cascade of reactions, including protein A (RPA) complex loading onto single-stranded DNA ATR activator chromatin. The contribution histone modifications to activation, however, is unclear. Here, we report that H3K14 trimethylation responds by enhancing activation. First, confirmed monomethylation, dimethylation, all exist in mammalian cells, both SUV39H1 SETD2 methyltransferases can catalyze vivo...
Abstract The tumor suppressor p53 has critical roles in regulating lipid metabolism, but whether and how regulates cardiolipin (CL) de novo biosynthesis is unknown. Here, we report that physically interacts with histone deacetylase SIRT6 vitro vivo, this interaction increases following palmitic acid (PA) treatment. In response to PA, localize chromatin a p53-dependent manner. Chromatin bind the promoters of CDP-diacylglycerol synthase 1 2 ( CDS1 CDS2 ), two enzymes required catalyze CL...
Mutations of <i>PTEN-induced kinase I</i> (<i>PINK1</i>) cause early-onset Parkinson's disease (PD) with selective neurodegeneration in humans. However, current <i>PINK1</i> knockout mouse and pig models are unable to recapitulate the typical neurodegenerative phenotypes observed PD patients. This suggests that generating non-human primates (NHPs) close humans is essential investigate unique function PINK1 primate brains. Paired single guide RNA (sgRNA)/Cas9-D10A nickases truncated...
Abstract Common unintended chromosomal alterations induced by CRISPR/Cas9 in mammalian cells, particularly on-target large deletions and translocations present a safety challenge for genome editing. Base editing prime that can precisely introduce desired edits without double-stranded breaks exogenous DNA templates face their own challenges. Thus, there is still an unmet need to develop safer more efficient tools. We screened diverse polymerases of distinct origins identified T4 polymerase...
An exposure that is reproducible across clinical/laboratory environments, and appealing to subjects, described here. Digital music files are level-equated within songs such playlists deliver an consistent time. Modified more pleasant listen than pure tones or shaped noise, closely follows exposures subjects may normally experience. Multiple therapeutics reduce noise-induced hearing loss in animals but human trial design complicated by limited access noise-exposed subject populations. The...
The aim of this study was to investigate the effect and possible mechanism action roof plate-specific spondin1 (Rspo1) in apoptosis rat bone marrow mesenchymal stem cells (BMSCs).Osteogenic adipogenic differentiation BMSCs identified by Alizarin Red Oil O staining, respectively. BMSC surface markers (cluster 29 [CD29], CD90, CD45) were detected using flow cytometry. transfected with an adenoviral vector encoding Rspo1 (BMSCs-Rspo1 group). expression levels gene protein BMSCs-Rspo1 group two...
Altered protein conformation can cause incurable neurodegenerative disorders. Mutations in SERPINI1 , the gene encoding neuroserpin, alter resulting cytotoxic aggregation neuronal endoplasmic reticulum. Aggregates oxidative stress impairing function, leading to death. Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare autosomal dominant progressive myoclonic epilepsy. Patients present seizures and cognitive impairments that progress dementia premature We developed...
Abstract Mutations of PINK1 cause early-onset Parkinson’s disease (PD) with selective neurodegeneration in humans. However,current knockout mouse and pig models are unable to recapitulate the typical neurodegenerative phenotypes observed PD patients, indicating that it is essential generate non-human primates (NHPs) highly close humans, investigate unique function primate brains. Paired single guide RNA (sgRNA)/Cas9-D10A nickases truncated sgRNA/Cas9, both enabling reduction off-target...
<h3></h3> Gene expression profiling of very few or even single cells is particular interest in many applications, including molecular diagnosis. However, detection a large number mRNA sequences from small limited by the sensitivity available methods. High-throughput multiplex reverse transcription followed PCR amplification (RT-PCR) has much to offer these studies owing its inherent sensitivity, efficiency, and cost-effectiveness. A RT-PCR-based high-throughput gene system described this...
Objective:To explore the clinical efficacy analysis surgery of posterior approach parotid gland resection preserving retinal ganglion and fascia for treatment benign tumour.Method:One hundred twelve cases were randomly divided into control group group. The was treated by anterior region fascia. data operation time, postoperative local numbness, Frey syndrome, facial paralysis recurrence case analyzed. Result:There no in both two groups, there significant difference between groups time...