Biography
Dr Mark Skidmore was appointed as Lecturer in Biochemistry at Keele in October 2010, having spent 4 years as Research Associate at Liverpool University, where he had previously completed his PhD in 2006 on “Heparin / heparan sulphate method development and protein interactions” under the supervision of Prof JE Turnbull and Dr EA Yates.
His first degree and diploma in Biochemistry were at Imperial College London, and he has built up a range of links across academic collaborations and industrial partnerships.
Research and scholarship
The general area of Dr Skidmore’s research interests is carbohydrate chemistry/biochemistry, in particular the role of anionic carbohydrates (for example the glysoaminoglycans (GAGs) as dynamic cell regulators.
The major focus of his current research is the study of carbohydrate:protein structure-functions, in particular the development of new tools and technologies for elucidating protein-carbohydrate interactions and their application to biomedical sciences, biological sciences and medicine.
Selected Publications
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Analysis of Heparin Samples by Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy in the Solid State. ACS CENTRAL SCIENCE. link> doi> full text>2023.
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Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction. ACS Cent Sci, 527-545, vol. 8(5). link> doi> full text>2022.
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The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models. Front Pharmacol, 660490, vol. 12. link> doi> full text>2021.
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Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin. Thromb Haemost, 1700-1715, vol. 120(12). link> doi> full text>2020.
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High sensitivity (zeptomole) detection of BODIPY-labelled heparan sulfate (HS) disaccharides by ion-paired RP-HPLC and LIF detection enables analysis of HS from mosquito midguts. Anal Methods, 1461-1469, vol. 15(11). link> doi> full text>2023.
Full Publications Listshow
Journal Articles
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Analysis of Heparin Samples by Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy in the Solid State. ACS CENTRAL SCIENCE. link> doi> full text>2023.
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High sensitivity (zeptomole) detection of BODIPY-labelled heparan sulfate (HS) disaccharides by ion-paired RP-HPLC and LIF detection enables analysis of HS from mosquito midguts. Anal Methods, 1461-1469, vol. 15(11). link> doi> full text>2023.
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A sulphated glycosaminoglycan extract from Placopecten magellanicus inhibits the Alzheimer's disease β-site amyloid precursor protein cleaving enzyme 1 (BACE-1). Carbohydr Res, 108747, vol. 525. link> doi> full text>2023.
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Evidence for Multiple Binding Modes in the Initial Contact Between SARS-CoV-2 Spike S1 Protein and Cell Surface Glycans. Chemistry, e202202599, vol. 29(1). link> doi> full text>2023.
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Analysis of protein-heparin interactions using a portable SPR instrument. PeerJ Analytical Chemistry, 1-16, vol. 4. doi> link> full text>2022.
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Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction. ACS Cent Sci, 527-545, vol. 8(5). link> doi> full text>2022.
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The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models. Front Pharmacol, 660490, vol. 12. link> doi> full text>2021.
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Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer's Disease β Secretase, BACE1. Mar Drugs, vol. 19(4). link> doi> full text>2021.
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Evidence of a putative glycosaminoglycan binding site on the glycosylated SARS-CoV-2 spike protein N-terminal domain. Comput Struct Biotechnol J, 2806-2818, vol. 19. link> doi> full text>2021.
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Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin. Thromb Haemost, 1700-1715, vol. 120(12). link> doi> full text>2020.
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Development of a nano-luciferase based assay to measure the binding of SARS-CoV-2 spike receptor binding domain to ACE-2. Biochem Biophys Res Commun, 485-490, vol. 534. link> doi> full text>2021.
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Molecular Changes in Dengue Envelope Protein Domain III upon Interaction with Glycosaminoglycans. Pathogens, vol. 9(11). link> doi> full text>2020.
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Unfractionated heparin inhibits live wild type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations. Br J Pharmacol, 626-635, vol. 178(3). link> doi> full text>2021.
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Glycosaminoglycans induce conformational change in the SARS-CoV-2 Spike S1 Receptor Binding Domain. doi>2020.
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SARS-CoV-2 Spike S1 Receptor Binding Domain undergoes Conformational Change upon Interaction with Low Molecular Weight Heparins. doi>2020.
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Heparin inhibits cellular invasion by SARS-CoV-2: structural dependence of the interaction of the surface protein (spike) S1 receptor binding domain with heparin. doi>2020.
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The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 Receptor Binding Domain undergoes conformational change upon heparin binding. doi>2020.
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Inhibition of BACE1, the β-secretase implicated in Alzheimer's disease, by a chondroitin sulfate extract from Sardina pilchardus. Neural Regen Res, 1546-1553, vol. 15(8). link> doi> full text>2020.
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Tools for the Quality Control of Pharmaceutical Heparin. Medicina, 636, vol. 55(10). doi> link> full text>2019.
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A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer's Disease. Mar Drugs, vol. 17(5). link> doi> full text>2019.
- 2018.
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The role of heparan sulfate in host macrophage infection by Leishmania species. Biochem Soc Trans, 789-796, vol. 46(4). link> doi> full text>2018.
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An Inexpensive, Pulsed, and Multiple Wavelength Bench-Top Light Source for Biological Spectroscopy. Plasma, vol. 1(1). doi> link> full text>2018.
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Subverting the mechanisms of cell death: flavivirus manipulation of host cell responses to infection. Biochem Soc Trans, 609-617, vol. 46(3). link> doi> full text>2018.
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Variations in the Peritrophic Matrix Composition of Heparan Sulphate from the Tsetse Fly, Glossina morsitans morsitans. Pathogens, vol. 7(1). link> doi> full text>2018.
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In vitro investigations on the effects of semi-synthetic, sulphated carbohydrates on the immune status of cultured common carp (Cyprinus carpio) leucocytes. Fish and Shellfish Immunology. link> doi> link> full text>2017.
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Identification of Heparin Modifications and Polysaccharide Inhibitors of Plasmodium falciparum Merozoite Invasion That Have Potential for Novel Drug Development. Antimicrob Agents Chemother, vol. 61(11). link> doi> full text>2017.
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A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium falciparum cytoadherence. PLoS One, e0186276, vol. 12(10). link> doi> full text>2017.
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Heparin prevents Zika virus induced-cytopathic effects in human neural progenitor cells. Antiviral Res, 13-17, vol. 140. link> doi> full text>2017.
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19F labelled glycosaminoglycan probes for solution NMR and non-linear (CARS) microscopy. Glycoconj J, 405-410, vol. 34(3). link> doi> full text>2017.
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Heat Dissipation of Hybrid Iron Oxide-Gold Nanoparticles in an Agar Phantom. Journal of Nanomedicine and Nanotechnology. doi> full text>2015.
- 2015.
- 2015.
- 2012.
- 2011.
- 2011.
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Disaccharide compositional analysis of heparan sulfate and heparin polysaccharides using UV or high-sensitivity fluorescence (BODIPY) detection. NATURE PROTOCOLS. doi>2010.
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The conformation and structure of GAGs: recent progress and perspectives. Current Opinions in structural biology, 567-574. doi>2010.
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Comparable stabilization, structural changes and activites can be induced in FGF by a variety of HS and non-GAG analogues: Implications for sequence-activity relationships. ORGANIC AND BIOMOLECULAR CHEMISTRY. doi>2010.
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The latent ampholytic nature of glycosaminoglycan (GAG) oligosaccharides facilitates their separation by isoelectric focusing. ANALYTICAL METHODS, 1550-1554, vol. 2(10).2010.
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The potential for circular dichroism as an additional facile and sensitive method of monitoring low-molecular-weight heparins and heparinoids. THROMBOSIS AND HAEMOSTASIS, 874-878, vol. 102(5). doi>2009.
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Rapid purification and high sensitivity analysis of heparan sulfate from cells and tissues: toward glycomics profiling. JOURNAL OF BIOLOGICAL CHEMISTRY, 25714-25722, vol. 284. doi>2009.
- 2008.
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Cations modulate polysaccharide structure to determine FGF-FGFR signaling: a comparison of signaling and inhibitory polysaccharide interactions with FGF-1 in solution. BIOCHEMISTRY, 4772-4779, vol. 48. doi>2009.
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Glycosaminoglycan origin and structure revealed by multivariate analysis of NMR and CD spectra. GLYCOBIOLOGY, 52-67, vol. 19. doi>2009.
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Labelling heparan sulphate saccharides with chromophore, fluorescence and mass tags for HPLC and MS separations. METHODS IN MOLECULAR BIOLOGY, 157-169, vol. 534.2009.
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Site-specific interactions of copper(II) ions with heparin revealed with complementary (SRCD, NMR, FTIR and EPR) spectroscopic techniques. CARBOHYDRATE RESEARCH, 2184-2193, vol. 343. doi>2008.
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Disruption of rosetting in Plasmodium falciparum malaria with chemically modified heparin and low molecular weight derivatives, possessing reduced anticoagulant and other serine protease inhibition activities. JOURNAL OF MEDICINAL CHEMISTRY, 1453-1458, vol. 51. doi>2008.
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The activities of the cell surface expressed glycosaminoglycan heparan sulfate and its analogue heparin are dictated by biosynthesis, sequence and conformation. CONNECTIVE TISSUE RESEARCH, 140-144, vol. 49.2008.
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Influence of substitution pattern and cation binding on conformation and activity in heparin derivatives. GLYCOBIOLOGY, 983-993, vol. 17(9). doi>2007.
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High sensitivity separation and detection of heparin / heparan sulfate disaccharides. JOURNAL OF CHROMATOGRAPHY A, 52, vol. 1135(1). doi>2006.
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Attachment of glycosaminoglycan oligosaccharides to thiol-derivatised gold surfaces. CHEMICAL COMMUNICATIONS, 2700, vol. 7(23). doi>2004.
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In vitro investigations on the effects of different polysaccharides structure and form on common carp (Cyprinus carpio) immune properties. PH.D. project publication.2017.
Chapters
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Revealing the hidden dimensions of GAGs in solution and protein complexes with saccharide libraries, FTIR and SRCD. In GLYCOBIOLOGY. SAMSON C and MARKHAM O (Eds.). BLOXHAM, UK: SCION.2007.
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Sequencing and separation of heparan sulfate. In Chemistry and Biology of Heparin and Heparan sulfate. GARG H, LINHARDT R, HALES C (Eds.). NEW YORK, USA: ELSEVIER B.V..2005.
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Surface-Based Studies of Heparin/Heparan Sulfate-Protein Interactions. In Chemistry and Biology of Heparin and Heparan sulfate. GARG H, LINHARDT R, HALES C (Eds.). NEW YORK, USA: ELSEVIER B.V..2005.
Other
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12th International Congress of Parasitology (ICOPA).
Funding
Dr Skidmore’s current research grants include:
- Principal applicant and student supervisor: “Novel glycotherapeutics for Alzheimer's disease”. (Co-Is: Prof S Allin, Dr EA Yates, Dr MJ McKenzie, Dr P Horrocks) Medical Research Council industrial CASE studentship MR/J012246/1 with Charnwood Molecular Ltd, £109,288
- Co-applicant and co-author: “Novel semi-synthetic carbohydrates as potential therapeutics for severe malaria” (PI: Dr EA Yates) Medical Research Council £554,479
- Co-applicant and co-author: “Chemically modified low molecular weight heparins as potent disruptors of rosetting in severe malaria”. (PI: Dr EA Yates) Wellcome £59,769
- Collaborator : “Investigation into Plasmodium falciparum rosetting mechanisms and development of rosette-disrupting interventions to treat or prevent severe malaria”. PI Alex Rowe – Wellcome Trust Senior Research Fellowship.
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