A5075340838- Molecular Biology Techniques and Applications
- Bioinformatics and Genomic Networks
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Wound Healing and Treatments
- Gene expression and cancer classification
- Viral Infectious Diseases and Gene Expression in Insects
- Endoplasmic Reticulum Stress and Disease
- Genetic and Kidney Cyst Diseases
- Hedgehog Signaling Pathway Studies
- Cellular transport and secretion
- Hippo pathway signaling and YAP/TAZ
- Fungal and yeast genetics research
- Protein Kinase Regulation and GTPase Signaling
- Renal and related cancers
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- bioluminescence and chemiluminescence research
- Viral gastroenteritis research and epidemiology
- Cell Adhesion Molecules Research
- Microtubule and mitosis dynamics
- Tendon Structure and Treatment
- RNA regulation and disease
Wirral University Teaching Hospital NHS Foundation Trust
2024
Thermo Fisher Scientific (United States)
2023
Baxter (United States)
2016-2022
Stanford University
2016-2022
Jackson Laboratory
2022
Stanford Medicine
2021
Creative Commons
2021
University of Rochester
2013-2019
Stratford University
2019
Abstract During aging, the regenerative capacity of muscle stem cells (MuSCs) decreases, diminishing ability to repair following injury. We found that MuSCs regenerate is regulated by primary cilium, a cellular protrusion serves as sensitive sensory organelle. Abolishing MuSC cilia inhibited proliferation in vitro and severely impaired injury-induced regeneration vivo. In aged muscle, cell intrinsic defect ciliation was associated with decrease capacity. Exogenous activation Hedgehog...
Abstract E2F transcription factors are central regulators of cell division and fate decisions. E2F4 often represents the predominant activity in cells. is a transcriptional repressor implicated cycle arrest whose repressive depends on its interaction with members RB family. Here we show that important for proliferation survival mouse embryonic stem In these cells, acts part as activator promotes expression genes. This role independent Furthermore, functionally interacts chromatin associated...
Rotaviruses (RVs) are the leading cause of severe gastroenteritis in young children, accounting for half a million deaths annually worldwide. RV encodes non-structural protein 1 (NSP1), well-characterized interferon (IFN) antagonist, which facilitates virus replication by mediating degradation host antiviral factors including IRF3 and β-TrCP. Here, we utilized six human animal NSP1s as baits performed tandem-affinity purification coupled with high-resolution mass spectrometry to...
Significance Many clinically significant human viral and bacterial pathogens use dynamin-dependent endocytosis to initiate infection or deliver toxin into host cells. Owing the complex nature of this cellular process, molecular mechanisms that regulate pathway remain be fully elucidated. Here, we rotavirus (RV) as a model identify drebrin regulatory protein restricts cell entry multiple viruses. We demonstrate genetic depletion chemical inhibition leads enhanced RV in vitro increased...
Primary cilia in many cell types contain a periaxonemal subcompartment called the inversin compartment. Four proteins have been found to assemble within compartment: INVS, ANKS6, NEK8, and NPHP3. The function of compartment is unknown, but it appears be critical for normal development, including left-right asymmetry renal tissue homeostasis. Here we combine superresolution imaging human RPE1 cells, classic model studying primary vitro, with genetic dissection protein-protein binding...
Abstract Activating mutations in RAS GTPases drive many cancers, but limited understanding of less-studied interactors, and the specific roles different interactor paralogs, continues to limit target discovery. We developed a multistage discovery screening process systematically identify genes conferring RAS-related susceptibilities lung adenocarcinoma. Using affinity purification mass spectrometry, we generated protein–protein interaction map interactors pathway components containing...
During tissue repair, fibronectin is converted from a soluble, inactive form into biologically active extracellular matrix (ECM) fibrils through cell-dependent process. ECM promotes numerous cell processes that are critical to repair and regulates the assembly of other proteins matrix. Nonhealing wounds show reduced levels fibronectin. To functionally mimic fibronectin, series mimetics was developed by directly coupling matricryptic, heparin-binding fragment first type III repeat (FNIII1H)...
Cilia are essential organelles and variants in genes governing ciliary function result ciliopathic diseases. The Ciliogenesis PLANar polarity Effectors (CPLANE) protein complex is for ciliogenesis animals models but remains poorly defined. Notably, all one subunit of the CPLANE have been implicated human ciliopathy. Here, we identify three families which remaining
Platelet-derived growth factor (PDGF) signaling is dysregulated in a wide variety of diseases, making PDGF an attractive therapeutic target. However, also affects numerous cascades essential for tissue homeostasis, limiting the development PDGF-based therapies that lack adverse side-effects. Recent studies showed fibroblast-mediated assembly extracellular matrix (ECM) fibronectin fibrils attenuates PDGF-induced intracellular calcium release by selectively inhibiting phosphoinositol 3-kinase...
<h3>Introduction</h3> The covid pandemic has further highlighted the role of viral infections in respiratory disease and importance recognition testing, including for Respiratory syncytial virus (RSV). RSV is prevalent childhood admissions however adult populations hospital not fully understood. It estimated that mortality as high 178 per 100,000 risk groups.<sup>1</sup> A vaccination programme adults aged 75 years above due to commence UK Autumn 2024. <h3>Methods</h3> We performed a...
Summary Regeneration is the “holy grail” of tissue repair, but skin injury typically yields fibrotic, non-functional scars. Developing pro-regenerative therapies requires rigorous understanding molecular progression from to fibrosis or regeneration. Here, we report divergent events driving wound cells toward either scarring regenerative fates. We profile versus YAP inhibition-induced regeneration at transcriptional (single-cell RNA-sequencing), protein (timsTOF proteomics), and...
ARHGAP36 is an atypical Rho GTPase-activating protein (GAP) family member that drives both spinal cord development and tumorigenesis, acting in part through N-terminal motif suppresses kinase A activates Gli transcription factors. also contains isoform-specific sequences, a central GAP-like module, unique C-terminal domain, the functions of these regions remain unknown. Here we have mapped structure-activity landscape using deep sequencing-based mutagenesis screen truncation mutant analyses....
ABSTRACT Activating mutations in RAS GTPases drive one fifth of cancers, but poor understanding many effectors and regulators, the roles their different paralogs, continues to impede drug development. We developed a multi-stage discovery screening process understand function identify RAS-related susceptibilities lung adenocarcinoma. Using affinity purification mass spectrometry (AP/MS), we generated protein-protein interaction map pathway containing thousands interactions. From this network...
Fasting causes insulin resistance in liver and fat, increases sensitivity muscle. We studied the response vitro vivo to of receptor tyrosine kinase muscle from 72 h fasted control rats. Insulin was injected intraperitoneally together with glucose, blood tissue samples were obtained 0, 5, 15 30 min later. Basal serum glucose levels significantly higher than fasting Serum rose approximately 300 mg/dl at 5 then progressively declined without hypoglycaemia. Receptors prepared whole by wheat germ...
Abstract Spatialomics is a rapidly growing field as it allows researchers to gain deeper understanding of transcriptomes and corresponding protein expression profiles in cells within complex tissue microenvironments. One critical technology for spatialomics in-situ hybridization (ISH) technology, which enables direct visualization quantitation nucleic acid with single molecule resolution. The Invitrogen ViewRNA ISH assays incorporate branched DNA (bDNA) provides tools interrogating multiple...
<div>Abstract<p>Activating mutations in RAS GTPases drive many cancers, but limited understanding of less-studied interactors, and the specific roles different interactor paralogs, continues to limit target discovery. We developed a multistage discovery screening process systematically identify genes conferring RAS-related susceptibilities lung adenocarcinoma. Using affinity purification mass spectrometry, we generated protein–protein interaction map interactors pathway...