A5050741985- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Chemokine receptors and signaling
- RNA Research and Splicing
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- DNA Repair Mechanisms
- RNA regulation and disease
- Monoclonal and Polyclonal Antibodies Research
- Mitochondrial Function and Pathology
- Pluripotent Stem Cells Research
- Liver Disease Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
- Endoplasmic Reticulum Stress and Disease
- Histone Deacetylase Inhibitors Research
- Synthesis and biological activity
- Viral Infections and Immunology Research
- Nutrition and Health in Aging
- MicroRNA in disease regulation
- Cancer-related gene regulation
- Body Composition Measurement Techniques
- GABA and Rice Research
Blood Center of Zhejiang Province
2024
University of Hull
2006-2024
University of Haripur
2024
Zhejiang University
2021-2024
University of Manchester
2021-2024
Hull York Medical School
2024
Manchester Academic Health Science Centre
2021-2024
University of North Carolina at Chapel Hill
2017-2023
University of Illinois Urbana-Champaign
2015-2022
UNC Lineberger Comprehensive Cancer Center
2017-2021
Histone acetylation levels are regulated by histone acetyltransferases (HATs) and deacetylases (HDACs) that antagonistically control the overall balance of this post-translational modification. HDAC inhibitors (HDACi) potent agents disrupt used clinically to treat diseases including cancer. Despite their use, little is known about effects on chromatin regulators, particularly those signal through lysine acetylation. We apply quantitative genomic proteomic approaches demonstrate HDACi...
A new copper(II) containing bis-macrocyclic CXCR4 chemokine receptor antagonist is shown to have improved binding properties the protein in comparison drug AMD3100 (Plerixafor, Mozobil). The interaction of metallodrug has been optimized by using ultrarigid chelator units that offer an equatorial site for coordination amino acid side chains protein. Binding competition assays with anti-CXCR4 antibodies show compound stays bound longer and it anti-HIV potency vitro (EC50 = 4.3 nM). X-ray...
Loss of the short arm chromosome 3 (3p) occurs early in >95% clear cell renal carcinoma (ccRCC). Nearly ubiquitous 3p loss ccRCC suggests haploinsufficiency for tumor suppressors as drivers tumorigenesis. We previously reported methyltransferase SETD2, which trimethylates H3 histones on lysine 36 (H3K36me3) and is located deletion, to also trimethylate microtubules 40 (αTubK40me3) during mitosis, with αTubK40me3 required genomic stability. now show that monoallelic, Setd2-deficient cells...
The chemokine receptor CXCR4 is implicated in multiple diseases including inflammatory disorders, cancer growth and metastasis, HIV/AIDS. targeting has been evaluated treating metastasis therapy resistance. Cyclam derivatives, most notably AMD3100 (Plerixafor™), are a common motif small molecule antagonists. However, not shown to be effective treatment as an individual agent. Configurational restriction transition metal complex formation increases binding affinity residence time. In the...
Heterochromatic domains are enriched with repressive histone marks, including H3 lysine 9 methylation, written by methyltransferases (KMTs). The pre-replication complex protein, origin recognition complex-associated (ORCA/LRWD1), preferentially localizes to heterochromatic regions in post-replicated cells. Its role heterochromatin organization remained elusive. ORCA recognizes methylated H3K9 marks and interacts KMTs, G9a/GLP Suv39H1 a chromatin context-dependent manner. Single-molecule...
Adenosine deaminases acting on RNA (ADARs) catalyze the editing of adenosine residues to inosine (A-to-I) within sequences, mostly in introns and UTRs (un-translated regions). The significance non-coding regions is poorly understood. Here, we demonstrate that association ADAR2 with stabilizes a subset transcripts. interacts edits 3΄UTR nuclear-retained Cat2 transcribed nuclear (Ctn RNA). In absence ADAR2, abundance half-life Ctn are significantly reduced. Furthermore, ADAR2-mediated...
DNA replication requires the recruitment of a pre-replication complex facilitated by Origin Recognition Complex (ORC) onto chromatin during G1 phase cell cycle. The ORC-associated protein (ORCA/LRWD1) stabilizes ORC on chromatin. Here, we evaluated genome-wide distribution ORCA using ChIP-seq specific time points G1. binding sites are dynamic and temporally regulated. association to genomic decreases as cells progressed towards S-phase. majority ORCA-bound represent origins that also...
Significance Transcriptional regulation of the rDNA cluster is a tightly regulated process owing to cellular demand for ribosomal subunits. Dysregulation biogenesis associated with genomic instability and tumor progression. Nucleolar-remodeling complex (NoRC) has emerged as key in maintenance repression. However, mechanisms that regulate association NoRC gene loci are yet be understood. We unravel role B ANP, E 5R, N ac1 (BEN) domain-containing transcription repressor, BEND3, regulating...
Breast cancer (BC) is a highly heterogeneous disease, both at the pathological and molecular level, several chromatin-associated proteins play crucial roles in BC initiation progression. Here, we demonstrate role of PSIP1 (PC4 SF2 interacting protein)/p75 (LEDGF) PSIP1/p75, previously identified as chromatin-adaptor protein, found to be upregulated basal-like/triple negative breast (TNBC) patient samples cell lines. Immunohistochemistry tissue arrays showed elevated levels metastatic...
BEN domain-containing proteins are emerging rapidly as an important class of factors involved in modulating gene expression, yet the molecular basis how they regulate chromatin function and transcription remains to be established. BEND3 is a quadruple protein that associates with heterochromatin functions transcriptional repressor. We find highly expressed pluripotent cells, induction differentiation results down-regulation BEND3. The removal from cells exhibiting upregulation...
Sarcopenia is associated with unfavourable long-term survival in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). However, the impact of myosteatosis and muscle loss on patient prognosis has not been investigated.
The copper(II) complex of a novel rhodamine-azamacrocycle conjugate binds to the CXCR4 chemokine receptor and competes effectively against anti-CXCR4 monoclonal antibodies. copper macrocycle unit adopts trans-II configuration in solid state.
The syntheses of configurationally restricted mono- and bis-macrocyclic copper(II) perchlorate complexes (copper(II) 5-benzyl-1,5,8,12-tetraazabicyclo[10.2.2]hexadecane dicopper(II) 5,5′-[1,4-phenylenebis(methylene)]-bis(1,5,8,12-tetraazabicyclo[10.2.2]hexadecane)) are reported the X-ray structure mono-macrocyclic complex has been determined. EXAFS studies on species in aqueous solution show that copper coordination spheres essentially identical to solid state structure, do not vary presence...
Adenosine deaminases acting on RNA ( ADAR s) are proteins that catalyse widespread A‐to‐I editing within sequences. We recently reported 2 edits and stabilizes nuclear‐retained Cat2 transcribed nuclear Ctn ). Here, we report 1 coordinates with to regulate stability of . observe an ‐dependent interaction between 2. Furthermore, negatively regulates ‐destabilizing proteins. also show breast cancer BC ) cells display elevated but not levels, compared nontumourigenic cells. Additionally,...
Transcription repression plays a central role in gene regulation. repressors utilize diverse strategies to mediate transcriptional repression. We have recently demonstrated that BEND3 (BANP, E5R and Nac1 domain) protein represses rDNA transcription by stabilizing NoRC component. discuss the of as global regulator expression propose model whereby associates with chromatin remodeling complexes modulate heterochromatin organization.
Multivalent binding is an efficient means to enhance the affinity and specificity of chemical probes targeting multidomain proteins in order study their function role disease. While theory multivalent straightforward, physical structural characterization bivalent encounters multiple technical difficulties. We present a case where combination experimental techniques computational simulations was used comprehensively characterize structure–affinity relationships for series Bromosporine-based...
Abstract Histone methyltransferases play essential roles in the organization and function of chromatin. They are also frequently mutated human diseases including cancer 1 . One such often methyltransferase, SETD2, associates co-transcriptionally with RNA polymerase II catalyzes histone H3 lysine 36 trimethylation (H3K36me3) – a modification that contributes to gene transcription, splicing, DNA repair 2 While studies on SETD2 have largely focused consequences its catalytic activity,...
The abundance of Myc protein must be exquisitely controlled to avoid growth abnormalities caused by too much or little Myc. An intriguing mode regulation exists in which itself leads reduction its abundance. We show here that dMyc binds the miR-308 locus and increases expression. Using our gain-of-function approach, we an increase causes a destabilization mRNA reduced levels. In vivo knockdown confirmed levels embryos. This regulatory loop is crucial for maintaining appropriate normal...
Abstract Saline-alkali stress is a widely distributed abiotic that severely limits plant growth. γ-Aminobutyric acid (GABA) accumulates rapidly in plants under saline-alkali stress, but the underlying molecular mechanisms and associated regulatory networks remain unclear. Here, we report MYB-like protein, I-box binding factor (SlMYBI), which positively regulates tolerance through induced GABA accumulation by directly modulating glutamate decarboxylase (GAD) gene SlGAD1 tomato (Solanum...