Andy West

Andy West
GlaxoSmithKline | GSK · Bioimaging

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24
Publications
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1,267
Citations

Publications

Publications (24)
Article
Tuberculosis, caused by the intracellular pathogen Mycobacterium tuberculosis , remains the world’s deadliest infectious disease. Sterilizing chemotherapy requires at least 6 months of multidrug therapy. Difficulty visualizing the subcellular localization of antibiotics in infected host cells means that it is unclear whether antibiotics penetrate a...
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Full-text available
Background: Poor adherence to inhaled drug therapy in individuals with asthma and/or chronic obstructive pulmonary disease (COPD) may be associated with suboptimal therapeutic outcomes. Measurement of drug residues in hair samples has been employed to assess oral medication use over time. Here we test the feasibility of analyzing hair samples from...
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We report the development of a 3D OrbiSIMS instrument for label-free biomedical imaging. It combines the high spatial resolution of secondary ion mass spectrometry (SIMS; under 200 nm for inorganic species and under 2 μm for biomolecules) with the high mass-resolving power of an Orbitrap (>240,000 at m/z 200). This allows exogenous and endogenous m...
Article
ToF-SIMS is a label free imaging method that has been shown to enable imaging of amiodarone in single rat macrophage (NR8383) cells. In this study, we show the method extends to three other cell lines relevant to drug discovery: Human embryonic kidney (HEK293), cervical cancer (HeLa) and liver cancer (HepG2). There is significant interest in the va...
Article
Inadequate target exposure is a major cause of high attrition in drug discovery. Here, we show that a label-free method for quantifying the intracellular bioavailability (Fic) of drug molecules predicts drug access to intracellular targets and hence, pharmacological effect. We determined Fic in multiple cellular assays and cell types representing d...
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Background Atopic eczema (AE) is characterized by skin barrier and immune dysfunction. Null mutations in filaggrin (FLG), a key epidermal barrier protein, strongly predispose to AE; however, the precise role of FLG deficiency in AE pathogenesis remains incompletely understood. Objectives We sought to identify global proteomic changes downstream of...
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There is an increasing need in the pharmaceutical industry to reduce drug failure at late stage and so reduce the cost of developing a new medicine. Since most drug targets are intracellular this requires a better understanding of the drug disposition within a cell. Secondary ion mass spectrometry has been identified as a potentially important tech...
Article
div class="title">A Novel Hybrid Dual Analyzer SIMS Instrument for Improved Surface and 3D-Analysis - Volume 22 Issue S3 - Alexander Pirkl, Rudolf Moellers, Henrik Arlinghaus, Felix Kollmer, Ewald Niehuis, Alexander Makarov, Stevan Horning, Melissa Passarelli, Rasmus Havelund, Paulina Rakowska, Alan Race, Alexander G. Shard, Andy West, Peter Marsha...
Article
Correlative NanoSIMS and EM imaging of amiodarone-treated macrophages shows the internalisation of the drug at a sub-cellular level and reveals its accumulation within the lysosomes, providing direct evidence for amiodarone-induced phospholipidosis. Chemical fixation using tannic acid effectively seals cellular membranes aiding intracellular retent...
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Blood evidence is frequently encountered at the scene of violent crimes and can provide valuable intelligence in the forensic investigation of serious offences. Because many of the current enhancement methods used by crime scene investigators are presumptive, the visualisation of blood is not always reliable nor does it bear additional information....
Article
Erratum to: J. Am. Soc. Mass Spectrom (2015) 26: 862–872 DOI 10.1007/s13361-015-1140-z An incorrect version of Figure 1e was shown in our recently published article. The correct structure is: Figure 1. (e) sodium 3-[(2-methyl-2-undecyl-1,3-dioxolan-4-yl)methoxyl]-1-propanesulfonate (RapiGest SF)
Article
One of the key challenges facing early stage drug discovery is understanding the commonly observed difference between the activity of compounds in biochemical assays and cellular assays. Traditionally, indirect or estimated cell permeability measurements such as estimations from logP or artificial membrane permeability are used to explain the diffe...
Article
Detecting metabolites and parent compound within a cell type is now a priority for pharmaceutical development. In this context, three-dimensional secondary ion mass spectrometry (SIMS) imaging was used to investigate the cellular uptake of the antiarrhythmic agent amiodarone, a phospholipidosis-inducing pharmaceutical compound. The high lateral res...
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Full-text available
Despite recent improvements to in situ proteolysis strategies, a higher efficiency is still needed to increase both the number of peptides detected and the associated ion intensity, leading to a complete and reliable set of biomarkers for diagnostic or prognostic purposes. In the study presented here, an extract of a systematic study is illustrated...
Article
RATIONALEThe signal intensity of a given molecule across a tissue section when measured using mass spectrometry imaging (MSI) is prone to changes caused by the molecular heterogeneity across the surface of the tissue. Here we propose a strategy to investigate these effects using electrospray ionization (ESI) and matrix-assisted laser desorption/ion...
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Full-text available
Using mass spectrometry to detect enzymatic activity offers several advantages over fluorescence-based methods. Automation of sample handling and analysis using platforms such as the RapidFire (Agilent Technologies, Lexington, MA) has made these assays amenable to medium-throughput screening (of the order of 100,000 wells). However, true high-throu...
Article
During early-stage drug development, drug and metabolite distribution studies are carried out in animal tissues using a range of techniques, particularly whole body autoradiography (WBA). While widely employed, WBA has a number of limitations, including the following: expensive synthesis of radiolabeled drugs and analyte specificity and identificat...
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Full-text available
To date matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) analysis has been largely concerned with mapping the distribution of known analytes in tissues. An important step in the progression of its applications is the determination of unknown variants for metabolite and protein profiling in both clinical studies and...
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Full-text available
Rosiglitazone (BRL 49653), a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist and potent insulin action-enhancing agent, was given in the diet (50 micromol/kg of diet) to male Zucker rats ages 6-7 weeks for 9 months (prevention group). In this treatment mode, rosiglitazone prolonged the time to onset of proteinuria from 3 to 6...

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Project (1)
Project
Establish methods for assessment of bioavailable intracellular concentrations