A5075156386- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- Peptidase Inhibition and Analysis
- Bacteriophages and microbial interactions
- Phenothiazines and Benzothiazines Synthesis and Activities
- Vascular Procedures and Complications
- Peripheral Artery Disease Management
- Lung Cancer Treatments and Mutations
- Enzyme Structure and Function
- HVDC Systems and Fault Protection
- Poxvirus research and outbreaks
- Bacillus and Francisella bacterial research
- Mitochondrial Function and Pathology
- Protein Structure and Dynamics
- Radiation Dose and Imaging
- Chromium effects and bioremediation
- Carcinogens and Genotoxicity Assessment
- Electron Spin Resonance Studies
- Berberine and alkaloids research
- ATP Synthase and ATPases Research
The University of Texas Health Science Center at San Antonio
2018-2025
The University of Texas Health Science Center at Houston
2020-2024
The University of Texas at San Antonio
2020-2024
University Hospitals Sussex NHS Foundation Trust
2017-2023
Cancer Research Institute of the Slovak Academy of Sciences
2020-2023
Icahn School of Medicine at Mount Sinai
2005-2021
Royal Sussex County Hospital
2018
Guy's and St Thomas' NHS Foundation Trust
2017
St Thomas' Hospital
2014
Guy's Hospital
2008
Collaboration among writers-readers-erasers of m 6 A regulates the stability tumor-specific genes.
Abstract The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 illness, has caused millions infections worldwide. In SARS coronaviruses, non-structural protein 16 (nsp16), in conjunction with nsp10, methylates 5′-end virally encoded mRNAs to mimic cellular mRNAs, thus protecting virus from host innate immune restriction. We report here high-resolution structure a ternary complex SARS-CoV-2 nsp16 and nsp10 presence cognate RNA substrate analogue...
Abstract Background RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in RBP expression and are often observed cancer influence critical pathways implicated tumor initiation growth. Identification characterization oncogenic RBPs their regulatory networks provide new opportunities for targeted therapy. Results We identify the protein SERBP1 a novel regulator glioblastoma (GBM) development. High is prevalent GBMs correlates with poor patient survival...
Abstract Osteosarcoma is the most common malignancy of bone, yet survival for patients with osteosarcoma virtually unchanged over past 30 years. This principally because development new therapies hampered by a lack recurrent mutations that can be targeted in osteosarcoma. Here, we report epigenetic changes via mRNA methylation holds great promise to better understand mechanisms growth and develop therapeutics. In osteosarcoma, RNA demethylase ALKBH5 was amplified higher expression correlated...
An innovative analytical/computational approach is presented to provide maximum allowed probabilities (MAPs) of conformations in protein domains not rigidly connected. The applied calmodulin and its adduct with α-synuclein. Calmodulin a constituted by two rigid domains, each them composed calcium-binding EF-hand motifs, which solution are largely free move respect one another. We used the N60D mutant calmodulin, had been engineered selectively bind paramagnetic lanthanide ion only four...
Analysis of crystal structure elucidates the mechanism by which a human enzyme acts as both primase and DNA polymerase.
Type III R-M enzymes were identified >40 years ago and yet there is no structural information on these multisubunit enzymes. Here we report the structure of a system, consisting entire EcoP15I complex (Mod2Res1) bound to DNA. The suggests how ATP hydrolysis coupled long-range diffusion helicase DNA, dimeric methyltransferase functions methylate only one two DNA strands. We show that motor domains are specifically adapted bind double-stranded facilitate sliding via novel 'Pin' domain. also...
Significance For over three decades, bisphosphonates have been used for the therapy of osteoporosis and skeletal metastasis. Here we show that this class drugs reduces viability tumor cells are driven by human epidermal growth factor receptor (HER) family tyrosine kinases. We also directly bind to inhibit HER Because inexpensive readily available worldwide, our findings may important healthcare implications offering an affordable multiuse alternative or adjunct current therapies HER-driven...
Significance Small molecules to target oncogenic signaling cascades in cancer have achieved success molecularly defined patient subsets. The path approval is often protracted and plagued with failures. Repositioning Food Drug Administration-approved drugs known side effects has become a major focus. Bisphosphonates are commonly prescribed therapy for osteoporosis skeletal metastases. also been associated reduced tumor burden some patients, but the mechanism unknown. Here we provide evidence...
Methyltransferase like-3 (METTL3) and METTL14 complex transfers a methyl group from S-adenosyl-L-methionine to N6 amino of adenosine bases in RNA (m6A) DNA (m6dA). Emerging evidence highlights role METTL3-METTL14 the chromatin context, especially processes where are held close proximity. However, mechanistic framework about specificity for substrate RNA/DNA their interrelationship remain unclear. By systematically studying methylation activity binding affinity number oligos with different...
Interventional radiology is a key service in all hospitals the UK.Interventional units vary size depending on of hospital, services provided by hospital and their proximity to other units.All patients should have access emergency interventional procedures whenever they require them.This will network arrangement between some cases.An out-of-hours oncall rota at least one six minimum standard that exist.A wide number clinical conditions are treated radiologists grows year year.Some basic can...
The nuclear METTL3-METTL14 transfers a methyl group from SAM to convert the N 6 of adenosine (A) in RNA m A and ssDNA 6mA. marks are prevalent eukaryotic mRNAs lncRNAs modulate their stability fate context-dependent manner. cytoplasmic METTL3 can act as reader. However, precise mechanism during m6A writing, reading, or sensing is unclear. Here, we present ~2.5 Å structure methyltransferase core human complex with reaction product mimic, -methyladenosine monophosphate (m A), representing...
The nuclear METTL3-METTL14 transfers a methyl group from SAM to convert the N 6 of adenosine (A) in RNA m A and ssDNA 6mA. marks are prevalent eukaryotic mRNAs lncRNAs modulate their stability fate context-dependent manner. cytoplasmic METTL3 can act as reader. However, precise mechanism during m6A writing, reading, or sensing is unclear. Here, we present ~2.5 Å structure methyltransferase core human complex with reaction product mimic, -methyladenosine monophosphate (m A), representing...
RNA binding proteins have emerged as critical oncogenic factors and potential targets in cancer therapy. In this study, we evaluated Musashi1 (Msi1) targeting a strategy to treat glioblastoma (GBM); the most aggressive brain tumor type. Msi1 expression levels are often high GBMs other types correlate with poor clinical outcome. Moreover, has been implicated chemo- radio-resistance. modulates range of relevant processes pathways regulates stem cell markers via mRNA translation/stability. To...
Abstract The SARS-CoV-2 nsp16/nsp10 enzyme complex modifies the 2′-OH of first transcribed nucleotide viral mRNA by covalently attaching a methyl group to it. 2′- O methylation converts status cap from Cap-0 Cap-1, and thus, helps virus evade immune surveillance in host cells. Here, we report two structures representing pre- post-release states RNA product (Cap-1). We observe overall widening upon formation, an inward twisting motion substrate binding region release. These conformational...
Abstract This study examines the level of knowledge applied clinical anatomy among junior doctors. A multiple‐choice questionnaire was designed, which covered 15 areas anatomical essential to practice, for example, important surface landmarks and interpretation radiographs. The completed by 128 individuals. They comprised demonstrators, preregistration house officers (PRHOs), senior (SHOs) specialist registrars (SpRs) across range medical surgical specialities. Answers were scored analyzed...
Monkeypox virus (MPXV) infections in humans have historically been restricted to regions of endemicity Africa. However, 2022, an alarming number MPXV cases were reported globally, with evidence person-to-person transmission. Because this, the World Health Organization (WHO) declared outbreak a public health emergency international concern. The supply vaccines is limited, and only two antivirals, tecovirimat brincidofovir, approved by U.S. Food Drug Administration (FDA) for treatment...
Unrepaired oxidatively-stressed replication forks can lead to chromosomal instability and neoplastic transformation or cell death. To meet these challenges cells have evolved a robust mechanism repair oxidative genomic DNA damage through the base excision (BER) pathway, but less is known about of at forks. We found that depletion genetic deletion EEPD1 decreases clonogenic survival after damage. demonstrate recruited stressed by induced H
In this study we have identified POLθ-S6K-p62 as a novel druggable regulator of radiation response in prostate cancer. Despite significant advances delivery, radiotherapy continues to negatively affect treatment outcomes and quality life due resistance late toxic effects the surrounding normal tissues such bladder rectum. It is essential develop new effective strategies achieve better control tumor. We found that ribosomal protein S6K (RPS6KB1) elevated human tumors, contributes radiation....