A5029546833- Corneal surgery and disorders
- Glaucoma and retinal disorders
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Corneal Surgery and Treatments
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Retinal Development and Disorders
- Autophagy in Disease and Therapy
- RNA modifications and cancer
- Drug Transport and Resistance Mechanisms
- Sphingolipid Metabolism and Signaling
- Lipid metabolism and biosynthesis
- Epigenetics and DNA Methylation
- Circular RNAs in diseases
- RNA Interference and Gene Delivery
- Cholesterol and Lipid Metabolism
- Advanced Glycation End Products research
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Hedgehog Signaling Pathway Studies
- Mitochondrial Function and Pathology
- Connexins and lens biology
- RNA regulation and disease
- Parasitic Infections and Diagnostics
The University of Texas Southwestern Medical Center
2013-2024
Southwestern Medical Center
2012-2024
Hunan Normal University
2014-2024
Hunan Provincial People's Hospital
2015-2024
Southern University of Science and Technology
2020-2024
Huazhong Agricultural University
2021-2024
Changsha Hospital for Maternal and Child Health Care
2024
Hunan Agricultural University
2023
Center for Human Genetics
2023
Fourth Hospital of Changsha
2022
- The analysis of somatic mutations across multiple genes in cancer specimens may be used to aid clinical decision making. analytical validation targeted next-generation sequencing panels is important assess accuracy and limitations.- To report the development OncoPanel, a custom assay for cancer.- OncoPanel was designed detection single-nucleotide variants, insertions deletions, copy number alterations, structural variants 282 with evidence as drivers biology. We implemented strategy using...
The first step in Hedgehog signaling (Hh) pathway is important embryogenesis; overactivation associated with cancer. Central to the membrane receptor Patched 1 (Ptch1), which indirectly inhibits a G protein–coupled called Smoothened. This inhibition relieved when Ptch1 binds secreted protein Hh. Gong et al. report cryo–electron microscopy structures of human alone and complex its Hh ligand at 3.9 3.6 Å, respectively. Both include two steroid-shaped densities, mutational analysis indicates...
Upon oxidative stress cells show an increase in the oxidized glutathione (GSSG) to reduced (GSH) ratio with a concomitant decrease activity of ubiquitinylation pathway. Because most enzymes involved attachment ubiquitin substrate proteins contain active site sulfhydryls that might be covalently modified (thiolated) upon enhancement GSSG levels (glutathiolation), it appeared plausible glutathiolation alter rates cellular stress. This hypothesis was explored using intact retina and retinal...
Relations between the ubiquitin pathway and cellular stress have been noted, but data regarding responses of to oxidative are scanty. This paper documents response this in lens cells. A brief exposure epithelial cells physiologically relevant levels H2O2 induces a transient increase activity ubiquitin-dependent pathway. Ubiquitin conjugation was maximal increased 3.5–9.2-fold over noted untreated by 4 h after removal H2O2. By 24 H2O2, returned level In parallel changes activity,...
The ubiquitin–proteasome pathway (UPP) regulates critical cell processes, including the cycle, cytokine-induced gene expression, differentiation, and death. Recently we demonstrated that this responds to oxidative stress in mammalian cells proposed activities of ubiquitin-activating enzyme (E1) ubiquitin-conjugating enzymes (E2s) are regulated by cellular redox status (i.e., GSSG:GSH ratio). To test hypothesis, altered ratio retinal pigment epithelial with thiol-specific oxidant, diamide,...
Parkinson's disease (PD) is the most prevalent movement disorder characterized by selective loss of midbrain dopaminergic (DA) neurons. MicroRNA-124 (miR-124) abundantly expressed in DA neurons and its expression level decreases 1-methyl-4-pheny-1, 2, 3, 6-tetrahydropyridine (MPTP) model PD. However, whether upregulation miR-124 could attenuate neurodegeneration remains unknown. Here, we employed agomir mimics to upregulate MPTP-treated mice MPP(+) -intoxicated SH-SY5Y cells, respectively....
PURPOSE.We tested the association between two intronic polymorphisms (CTG18.1 and rs613872) in TCF4 Fuchs' endothelial corneal dystrophy (FECD), analyzed their segregation patterns families.METHODS.We recruited 120 unrelated Caucasian subjects with FECD 100 controls.Available family members of probands were recruited.Genotyping single nucleotide polymorphism (SNP) rs613872 was performed using Sanger sequencing or real-time allelic discrimination assay.The trinucleotide repeat polymorphism,...
Expansion of the intronic CTG18.1 triplet repeat locus within TCF4 contributes significant risk to development Fuchs' endothelial corneal dystrophy (FECD) in Eurasian populations, but mechanisms by which expanded repeats result degeneration endothelium have been hitherto unknown. The purpose this study was examine FECD samples for presence RNA nuclear foci, hallmark toxic RNA, as well evidence haploinsufficiency TCF4.Using fluorescence situ hybridization, we examined foci containing CUG...
The Hedgehog (Hh) pathway controls embryonic development and postnatal tissue maintenance regeneration. Inhibition of Hh receptor Patched (Ptch) by the ligands relieves suppression signaling cascades. Here, we report cryo-EM structure tetrameric Ptch1 in complex with palmitoylated N-terminal domain human Sonic hedgehog (ShhNp) at a 4:2 stoichiometric ratio. shows that four protomers are organized as loose dimer dimers. Each binds to one ShhNp through two distinct inhibitory interfaces,...
A cellular cholesterol sensor Cholesterol levels in cells are controlled by the sterol regulatory element–binding protein (SREBP) pathway. When cell has sufficient cholesterol, transcription factor that regulates metabolism is sequestered at endoplasmic reticulum membrane, but when depleted, released to activate expression of genes involved synthesis and uptake. Yan et al. determined structure a central complex human SREBP containing proteins Scap Insig-2. These two membrane-embedded undergo...
The major pathology in Parkinson's disease (PD) is neuron injury induced by degeneration of dopaminergic neurons and the activation microglial cells. objective this study to determine effect mechanism miR-132-3p regulating neuroinflammation PD. expressions brain tissues PD patients, lipopolysaccharide (LPS)-induced BV-2 cells 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse models were detected. GLRX cell viability, apoptosis inflammation was verified Iba1 substantia nigra...
Abstract The ORM/ORMDL family proteins function as regulatory subunits of the serine palmitoyltransferase (SPT) complex, which is initiating and rate-limiting enzyme in sphingolipid biosynthesis. This complex tightly regulated by cellular levels, but sensing mechanism unknown. Here we show that purified human SPT-ORMDL complexes are inhibited central metabolite ceramide. We have solved cryo-EM structure SPT-ORMDL3 a ceramide-bound state. Structure-guided mutational analyses reveal essential...
We have examined the level of 8-hydroxyguanosine (8-oxo-G), an oxidized form guanosine, in RNA Escherichia coli under normal and oxidative stress conditions. The 8-oxo-G rises rapidly remains high for hours response to hydrogen peroxide (H₂O₂) challenge a dose-dependent manner. H₂O₂ induced elevation content is much higher than that 8-hydroxydeoxyguanosine (8-oxo-dG) DNA. Under conditions, low isolated from ribosome it nearly three times non-ribosomal RNAs. In contrast, generated by short...
Ongoing cancer genome characterization studies continue to elucidate the spectrum of genomic abnormalities that drive many cancers, and in clinical arena assessment driver genetic alterations patients is playing an increasingly important diagnostic and/or prognostic role for types. However, landscape still unknown less common influence specific genotypes on behavior often unclear. To address some these deficiencies, we developed Profile, a prospective cohort study obtain information all at...
To test the association between CTG18.1 trinucleotide repeat expansion of TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Chinese population.The polymorphism was genotyped using short tandem triplet primed polymerase chain reaction assays 57 subjects with FECD 121 controls. Statistical expanded allele 18 single nucleotide polymorphisms (SNPs) across evaluated. investigate linkage disequilibrium structure region, haplotype analysis performed on our study compared genotyping...
Fuchs' endothelial corneal dystrophy (FECD) is the most common repeat expansion disorder. FECD impacts 4% of U.S. population and leading indication for transplantation. Most cases are caused by an expanded intronic CUG tract in TCF4 gene that forms nuclear foci, sequesters splicing factors impairs splicing. We investigated sense antisense RNA landscape at find sense-expanded transcript predominant species patient corneas. In tissue, foci number were negatively correlated with age showed no...
<h3>Importance</h3> The CTG18.1 triplet repeat expansion in<i>TCF4</i>has recently been found to be a common functional variant contributing significant risk the development of Fuchs endothelial corneal dystrophy (FECD) in Eurasian populations. <h3>Objectives</h3> To determine effect expanded allele of<i>TCF4</i>on FECD severity and correlate CTG length FECD. <h3>Design, Setting, Participants</h3> In cross-sectional analysis, we studied 139 index cases (probands unrelated individuals) with...
Abstract Human ATP-binding cassette (ABC) subfamily A (ABCA) transporters mediate the transport of various lipid compounds across membrane. Mutations in human ABCA have been described to cause severe hereditary disorders associated with impaired transport. However, little is known about mechanistic details substrate recognition and translocation by transporters. Here, we present three cryo-EM structures ABCA4, a retina-specific transporter, distinct functional states at resolutions 3.3–3.4...