Christopher J. Schofield

Chris Schofield attended St Anselm's College catholic grammar school in Merseyside, then studied for a Bachelor of Science in chemistry at the University of Manchester and graduated with a first class honour (1979–1982). In 1982, he moved to Oxford to study for a DPhil with Professor Jack E. Baldwin. In 1985, he became a Departmental Demonstrator in the Dyson Perrins Laboratory, Oxford University followed by his appointment as a Lecturer in Chemistry and a Fellow of Hertford College in 1990. In 1998, he became professor of Chemistry, and in 2011 he was appointed the Head of Organic Chemistry{{Cite web|url=http://selectbiosciences.com/conferences/biographies.aspx?conf=ewc2012&speaker=100755|title=SELECTBIO – Epigenetics Speaker Biography|website=SELECTBIO|access-date=2016-08-08}} at the Department of Chemistry, University of Oxford. In 2013, he was elected a Fellow of the Royal Society, FRS.{{Cite web|url=https://royalsociety.org/people/christopher-schofield-12241/|title=Christopher Schofield|publisher=royalsociety.org|access-date=2016-08-08}}

The work in laboratory of Chris Schofield focuses on different areas of research, including:

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric α,β-transcriptional complex{{Cite journal|last1=Wilkins|first1=Sarah E.|last2=Abboud|first2=Martine I.|last3=Hancock|first3=Rebecca L.|last4=Schofield|first4=Christopher J.|date=19 April 2016|title=Targeting Protein–Protein Interactions in the HIF System|journal=ChemMedChem|language=en|volume=11|issue=8|pages=773–786|doi=10.1002/cmdc.201600012|issn=1860-7187|pmc=4848768|pmid=26997519}} that mediates the cellular response to oxygen availability in multi-cellular organisms,{{Cite journal|last1=Jaakkola|first1=Panu|last2=Mole|first2=David R.|last3=Tian|first3=Ya-Min|last4=Wilson|first4=Michael I.|last5=Gielbert|first5=Janine|last6=Gaskell|first6=Simon J.|last7=Kriegsheim|first7=Alexander von|last8=Hebestreit|first8=Holger F.|last9=Mukherji|first9=Mridul|date=20 April 2001|title=Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation|journal=Science|language=en|volume=292|issue=5516|pages=468–472|doi=10.1126/science.1059796|issn=0036-8075|pmid=11292861|bibcode=2001Sci...292..468J|s2cid=20914281|doi-access=free}} ranging from the simplest known animal Trichoplax adhaerens to humans.{{Cite journal|last1=Epstein|first1=Andrew C. R.|last2=Gleadle|first2=Jonathan M.|last3=McNeill|first3=Luke A.|last4=Hewitson|first4=Kirsty S.|last5=O'Rourke|first5=John|last6=Mole|first6=David R.|last7=Mukherji|first7=Mridul|last8=Metzen|first8=Eric|last9=Wilson|first9=Michael I.|date=5 October 2001|title=C. elegans EGL-9 and Mammalian Homologs Define a Family of Dioxygenases that Regulate HIF by Prolyl Hydroxylation|journal=Cell|volume=107|issue=1|pages=43–54|doi=10.1016/S0092-8674(01)00507-4|pmid=11595184|doi-access=free}}{{Cite journal|last1=Ge|first1=Wei|last2=Wolf|first2=Alexander|last3=Feng|first3=Tianshu|last4=Ho|first4=Chia-hua|last5=Sekirnik|first5=Rok|last6=Zayer|first6=Adam|last7=Granatino|first7=Nicolas|last8=Cockman|first8=Matthew E.|last9=Loenarz|first9=Christoph|date=1 December 2012|title=Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans|journal=Nature Chemical Biology|language=en|volume=8|issue=12|pages=960–962|doi=10.1038/nchembio.1093|issn=1552-4450|pmc=4972389|pmid=23103944}}{{Cite journal|last1=Tian|first1=Ya-Min|last2=Yeoh|first2=Kar Kheng|last3=Lee|first3=Myung Kyu|last4=Eriksson|first4=Tuula|last5=Kessler|first5=Benedikt M.|last6=Kramer|first6=Holger B.|last7=Edelmann|first7=Mariola J.|last8=Willam|first8=Carsten|last9=Pugh|first9=Christopher W.|date=15 April 2011|title=Differential Sensitivity of Hypoxia Inducible Factor Hydroxylation Sites to Hypoxia and Hydroxylase Inhibitors|journal=Journal of Biological Chemistry|language=en|volume=286|issue=15|pages=13041–13051|doi=10.1074/jbc.M110.211110|issn=0021-9258|pmc=3075650|pmid=21335549|doi-access=free}} Investigating the structures and mechanisms of the HIF prolyl hydroxylases is a current focus of the work.{{Cite journal|last1=Loenarz|first1=Christoph|last2=Schofield|first2=Christopher J.|date=1 March 2008|title=Expanding chemical biology of 2-oxoglutarate oxygenases|journal=Nature Chemical Biology|language=en|volume=4|issue=3|pages=152–156|doi=10.1038/nchembio0308-152|issn=1552-4450|pmid=18277970}} The group solved crystal structures of PHD2{{Cite journal|last1=McDonough|first1=Michael A.|last2=Li|first2=Vivian|last3=Flashman|first3=Emily|last4=Chowdhury|first4=Rasheduzzaman|last5=Mohr|first5=Christopher|last6=Liénard|first6=Benoît M. R.|last7=Zondlo|first7=James|last8=Oldham|first8=Neil J.|last9=Clifton|first9=Ian J.|date=27 June 2006|title=Cellular oxygen sensing: Crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)|journal=Proceedings of the National Academy of Sciences|language=en|volume=103|issue=26|pages=9814–9819|doi=10.1073/pnas.0601283103|issn=0027-8424|pmc=1502536|pmid=16782814|bibcode=2006PNAS..103.9814M|doi-access=free}} - one of the human prolyl hydroxylases - and discovered that the HIF asparaginyl hydroxylase also catalyses hydroxylation of conserved motifs,{{Cite journal|last1=Yang|first1=Ming|last2=Chowdhury|first2=Rasheduzzaman|last3=Ge|first3=Wei|last4=Hamed|first4=Refaat B.|last5=McDonough|first5=Michael A.|last6=Claridge|first6=Timothy D. W.|last7=Kessler|first7=Benedikt M.|last8=Cockman|first8=Matthew E.|last9=Ratcliffe|first9=Peter J.|date=1 April 2011|title=Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post-translational hydroxylation of histidinyl residues within ankyrin repeat domains|journal=FEBS Journal|language=en|volume=278|issue=7|pages=1086–1097|doi=10.1111/j.1742-4658.2011.08022.x|issn=1742-4658|pmc=3569879|pmid=21251231}} the ankyrin repeat domain.

A current focus of the group is modification of histones, in particular oxygenase catalysed N-demethylation of histone methylated-lysine residues{{Cite journal|last1=Langley|first1=Gareth W.|last2=Brinkø|first2=Anne|last3=Münzel|first3=Martin|last4=Walport|first4=Louise J.|last5=Schofield|first5=Christopher J.|last6=Hopkinson|first6=Richard J.|date=25 November 2015|title=Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues|journal=ACS Chemical Biology|language=EN|volume=11|issue=3|pages=755–762|doi=10.1021/acschembio.5b00738|pmid=26555343|s2cid=19124771 |url=https://ora.ox.ac.uk/objects/uuid:443e77bb-ab24-4fd3-be98-fb6aa1a1b8b9}} – in collaboration with the Structural Genomics Consortium. The histone demethylases{{Cite journal|last1=Walport|first1=Louise J.|last2=Hopkinson|first2=Richard J.|last3=Chowdhury|first3=Rasheduzzaman|last4=Schiller|first4=Rachel|last5=Ge|first5=Wei|last6=Kawamura|first6=Akane|last7=Schofield|first7=Christopher J.|date=23 June 2016|title=Arginine demethylation is catalysed by a subset of JmjC histone lysine demethylases|journal=Nature Communications|language=en|volume=7|pages=11974|doi=10.1038/ncomms11974|pmc=4931022|pmid=27337104|bibcode=2016NatCo...711974W}}{{Cite journal|last1=Ng|first1=Stanley S.|last2=Kavanagh|first2=Kathryn L.|last3=McDonough|first3=Michael A.|last4=Butler|first4=Danica|last5=Pilka|first5=Ewa S.|last6=Lienard|first6=Benoit M. R.|last7=Bray|first7=James E.|last8=Savitsky|first8=Pavel|last9=Gileadi|first9=Opher|date=5 July 2007|title=Crystal structures of histone demethylase JMJD2A reveal basis for substrate specificity|journal=Nature|language=en|volume=448|issue=7149|pages=87–91|doi=10.1038/nature05971|issn=0028-0836|pmid=17589501|bibcode=2007Natur.448...87N|s2cid=4331492}} are of interest both with respect to their links to diseases, including cancer{{Cite journal|last1=Kawamura|first1=Akane|last2=Loenarz|first2=Christoph|last3=Schofield|first3=Christopher J.|date=1 September 2011|title=Mutations to metabolic enzymes in cancer herald a need to unify genetics and biochemistry|journal=Cell Cycle|volume=10|issue=17|pages=2819–2820|doi=10.4161/cc.10.17.16745|issn=1538-4101|pmid=21857150|doi-access=free}}{{Cite journal|last1=Rotili|first1=Dante|last2=Tomassi|first2=Stefano|last3=Conte|first3=Mariarosaria|last4=Benedetti|first4=Rosaria|last5=Tortorici|first5=Marcello|last6=Ciossani|first6=Giuseppe|last7=Valente|first7=Sergio|last8=Marrocco|first8=Biagina|last9=Labella|first9=Donatella|date=19 December 2013|title=Pan-Histone Demethylase Inhibitors Simultaneously Targeting Jumonji C and Lysine-Specific Demethylases Display High Anticancer Activities|journal=Journal of Medicinal Chemistry|language=EN|volume=57|issue=1|pages=42–55|doi=10.1021/jm4012802|pmid=24325601|hdl=11573/542432 }} and inflammatory diseases,{{Cite journal|last1=Kruidenier|first1=Laurens|last2=Chung|first2=Chun-wa|last3=Cheng|first3=Zhongjun|last4=Liddle|first4=John|last5=Che|first5=KaHing|last6=Joberty|first6=Gerard|last7=Bantscheff|first7=Marcus|last8=Bountra|first8=Chas|last9=Bridges|first9=Angela|date=16 August 2012|title=A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response|journal=Nature|language=en|volume=488|issue=7411|pages=404–408|doi=10.1038/nature11262|issn=0028-0836|pmc=4691848|pmid=22842901|bibcode=2012Natur.488..404K}} as well as the role of methylation in transcriptional regulation.{{Cite journal|last1=Lercher|first1=Lukas|last2=McDonough|first2=Michael A.|last3=El-Sagheer|first3=Afaf H.|last4=Thalhammer|first4=Armin|last5=Kriaucionis|first5=Skirmantas|last6=Brown|first6=Tom|last7=Schofield|first7=Christopher J.|s2cid=6489226|date=23 January 2014|title=Structural insights into how 5-hydroxymethylation influences transcription factor binding|journal=Chemical Communications|language=en|volume=50|issue=15|doi=10.1039/C3CC48151D|pmid=24287551|issn=1364-548X|pages=1794–1796|url=https://zenodo.org/record/894684}} Recent areas of interest include the fat mass and obesity protein{{Cite journal|last1=Church|first1=Chris|last2=Lee|first2=Sheena|last3=Bagg|first3=Eleanor A. L.|last4=McTaggart|first4=James S.|last5=Deacon|first5=Robert|last6=Gerken|first6=Thomas|last7=Lee|first7=Angela|last8=Moir|first8=Lee|last9=Mecinović|first9=Jasmin|date=14 August 2009|title=A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene|journal=PLOS Genet|volume=5|issue=8|pages=e1000599|doi=10.1371/journal.pgen.1000599|issn=1553-7404|pmid=19680540|pmc=2719869 |doi-access=free }}{{Cite journal|last1=Aik|first1=WeiShen|last2=Demetriades|first2=Marina|last3=Hamdan|first3=Muhammad K. K.|last4=Bagg|first4=Eleanor. A. L.|last5=Yeoh|first5=Kar Kheng|last6=Lejeune|first6=Clarisse|last7=Zhang|first7=Zhihong|last8=McDonough|first8=Michael A.|last9=Schofield|first9=Christopher J.|date=23 April 2013|title=Structural Basis for Inhibition of the Fat Mass and Obesity Associated Protein (FTO)|journal=Journal of Medicinal Chemistry|language=EN|volume=56|issue=9|pages=3680–3688|doi=10.1021/jm400193d|pmid=23547775}} which was shown to be a nucleic acid demethylase{{Cite journal|last1=Gerken|first1=Thomas|last2=Girard|first2=Christophe A.|last3=Tung|first3=Yi-Chun Loraine|last4=Webby|first4=Celia J.|last5=Saudek|first5=Vladimir|last6=Hewitson|first6=Kirsty S.|last7=Yeo|first7=Giles S. H.|last8=McDonough|first8=Michael A.|last9=Cunliffe|first9=Sharon|date=30 November 2007|title=The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase|journal=Science|language=en|volume=318|issue=5855|pages=1469–1472|doi=10.1126/science.1151710|issn=0036-8075|pmc=2668859|pmid=17991826|bibcode=2007Sci...318.1469G}} and JMJD6{{Cite journal|last1=Church|first1=Chris|last2=Lee|first2=Sheena|last3=Bagg|first3=Eleanor A. L.|last4=McTaggart|first4=James S.|last5=Deacon|first5=Robert|last6=Gerken|first6=Thomas|last7=Lee|first7=Angela|last8=Moir|first8=Lee|last9=Mecinović|first9=Jasmin|date=14 August 2009|title=A Mouse Model for the Metabolic Effects of the Human Fat Mass and Obesity Associated FTO Gene|journal=PLOS Genet|volume=5|issue=8|pages=e1000599|doi=10.1371/journal.pgen.1000599|issn=1553-7404|pmc=2719869|pmid=19680540 |doi-access=free }}{{Cite journal|last1=Mantri|first1=Monica|last2=Krojer|first2=Tobias|last3=Bagg|first3=Eleanor A.|last4=Webby|first4=Celia J.|last5=Butler|first5=Danica S.|last6=Kochan|first6=Grazyna|last7=Kavanagh|first7=Kathryn L.|last8=Oppermann|first8=Udo|last9=McDonough|first9=Michael A.|date=13 August 2010|title=Crystal Structure of the 2-Oxoglutarate- and Fe(II)-Dependent Lysyl Hydroxylase JMJD6|journal=Journal of Molecular Biology|volume=401|issue=2|pages=211–222|doi=10.1016/j.jmb.2010.05.054|pmid=20685276}} which is a lysyl hydroxylase modifying RNA splicing protein.

The 2-oxoglutarate (2OG)-dependent oxygenases are a superfamily of non-haem iron dependent oxygenases,{{Cite journal|last1=Clifton|first1=Ian J.|last2=McDonough|first2=Michael A.|last3=Ehrismann|first3=Dominic|last4=Kershaw|first4=Nadia J.|last5=Granatino|first5=Nicolas|last6=Schofield|first6=Christopher J.|date=1 April 2006|title=Structural studies on 2-oxoglutarate oxygenases and related double-stranded β-helix fold proteins|journal=Journal of Inorganic Biochemistry|series=High-valent iron intermediates in biologyHigh-valent iron intermediates in biology|volume=100|issue=4|pages=644–669|doi=10.1016/j.jinorgbio.2006.01.024|pmid=16513174}} most of which use the Krebs cycle intermediate, 2OG, as a co-substrate.{{Cite journal|last1=Welford|first1=Richard W.D.|last2=Kirkpatrick|first2=Joanna M.|last3=McNeill|first3=Luke A.|last4=Puri|first4=Munish|last5=Oldham|first5=Neil J.|last6=Schofield|first6=Christopher J.|date=5 December 2005|title=Corrigendum to "Incorporation of oxygen into the succinate co-product of iron(II) and 2-oxoglutarate dependent oxygenases from bacteria, plants and humans (FEBS 29930)" [FEBS Lett. 579 (2005) 5170–5174]|journal=FEBS Letters|language=en|volume=579|issue=29|pages=6688|doi=10.1016/j.febslet.2005.11.001|issn=1873-3468|doi-access=free|bibcode=2005FEBSL.579.6688W |hdl=10536/DRO/DU:30095401|hdl-access=free}} The group are interested in understanding these enzymes{{Cite journal|last1=Loenarz|first1=Christoph|last2=Mecinović|first2=Jasmin|last3=Chowdhury|first3=Rasheduzzaman|last4=McNeill|first4=LukeA.|last5=Flashman|first5=Emily|last6=Schofield|first6=ChristopherJ.|date=23 February 2009|title=Evidence for a Stereoelectronic Effect in Human Oxygen Sensing|journal=Angewandte Chemie International Edition|language=en|volume=48|issue=10|pages=1784–1787|doi=10.1002/anie.200805427|issn=1521-3773|pmid=19180614}} for their ability to catalyse synthetically difficult or 'impossible' reactions (e.g. the stereoselective hydroxylation of unactivated carbon-hydrogen bonds), for their diverse physiological roles, and for their links to disease.{{Cite journal|last1=Astuti|first1=Dewi|last2=Ricketts|first2=Christopher J.|last3=Chowdhury|first3=Rasheduzzaman|last4=McDonough|first4=Michael A.|last5=Gentle|first5=Dean|last6=Kirby|first6=Gail|last7=Schlisio|first7=Susanne|last8=Kenchappa|first8=Rajappa S.|last9=Carter|first9=Bruce D.|date=1 February 2011|title=Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility|url=http://erc.endocrinology-journals.org/content/18/1/73|journal=Endocrine-Related Cancer|language=en|volume=18|issue=1|pages=73–83|doi=10.1677/ERC-10-0113|issn=1351-0088|pmc=3006001|pmid=20959442}} The research focuses on members of the family that are linked to disease, or can be targeted for the treatment of disease.{{Cite journal|last1=Rose|first1=Nathan R.|last2=McDonough|first2=Michael A.|last3=King|first3=Oliver N. F.|last4=Kawamura|first4=Akane|last5=Schofield|first5=Christopher J.|date=14 July 2011|title=Inhibition of 2-oxoglutarate dependent oxygenases|journal=Chemical Society Reviews|language=en|volume=40|issue=8|doi=10.1039/C0CS00203H|issn=1460-4744|pages=4364–97|pmid=21390379}}{{Cite journal|last1=Aik|first1=WeiShen|last2=Scotti|first2=John S.|last3=Choi|first3=Hwanho|last4=Gong|first4=Lingzhi|last5=Demetriades|first5=Marina|last6=Schofield|first6=Christopher J.|last7=McDonough|first7=Michael A.|date=1 April 2014|title=Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation|journal=Nucleic Acids Research|language=en|volume=42|issue=7|pages=4741–4754|doi=10.1093/nar/gku085|issn=0305-1048|pmc=3985658|pmid=24489119}} Techniques involved in this interdisciplinary research include proteomics,{{Cite journal|last1=Mackeen|first1=Mukram M.|last2=Kramer|first2=Holger B.|last3=Chang|first3=Kai-Hsuan|last4=Coleman|first4=Matthew L.|last5=Hopkinson|first5=Richard J.|last6=Schofield|first6=Christopher J.|last7=Kessler|first7=Benedikt M.|date=21 July 2010|title=Small-Molecule-Based Inhibition of Histone Demethylation in Cells Assessed by Quantitative Mass Spectrometry|journal=Journal of Proteome Research|language=EN|volume=9|issue=8|pages=4082–4092|doi=10.1021/pr100269b|pmc=4681095|pmid=20583823}} X-ray crystallography,{{Cite journal|last1=Clifton|first1=Ian J.|last2=Hsueh|first2=Li-Ching|last3=Baldwin|first3=Jack E.|last4=Harlos|first4=Karl|last5=Schofield|first5=Christopher J.|date=15 December 2001|title=Structure of proline 3-hydroxylase|journal=European Journal of Biochemistry|language=en|volume=268|issue=24|pages=6625–6636|doi=10.1046/j.0014-2956.2001.02617.x|issn=1432-1033|pmid=11737217|doi-access=free}} nuclear magnetic resonance (NMR) spectroscopy,{{cite journal |vauthors=Mbenza NM, Vadakkedath PG, McGillivray DJ, Leung IK | title = NMR studies of the non-haem Fe(II) and 2-oxoglutarate-dependent oxygenases | journal = J. Inorg. Biochem. | volume = 177 | pages =384–394 |date=December 2017 | pmid = 28893416 | doi = 10.1016/j.jinorgbio.2017.08.032 }}{{cite journal |vauthors=Khan A, Leśniak RK, Brem J, Rydzik AM, Choi H, Leung IK, McDonough MA, Schofield CJ, Claridge TD | title = Development and application of ligand-based NMR screening assays for γ-butyrobetaine hydroxylase | journal = Med. Chem. Commun. | volume = 7 | issue = 5 | pages = 873–880 |date=February 2016 | doi = 10.1039/C6MD00004E | doi-access = free | hdl = 2292/30083 | hdl-access = free }}{{cite journal |vauthors=Leung IK, Demetriades M, Hardy AP, Lejeune C, Smart TJ, Szöllössi A, Kawamura A, Schofield CJ, Claridge TD | title = Reporter ligand NMR screening method for 2-oxoglutarate oxygenase inhibitors | journal = J. Med. Chem. | volume = 56 | issue = 2 | pages = 547–555 |date=January 2013 | pmid = 23234607 | doi = 10.1021/jm301583m | pmc=4673903}}{{cite journal |vauthors=Leung IK, Flashman E, Yeoh KK, Schofield CJ, Claridge TD | title = Using NMR solvent water relaxation to investigate metalloenzyme-ligand binding interactions | journal = J. Med. Chem. | volume = 53 | issue = 2 | pages = 867–875 |date=January 2010 | pmid = 20025281 | doi = 10.1021/jm901537q }}{{cite journal |vauthors=Rydzik AM, Leung IK, Thalhammer A, Kochan GT, Claridge TD, Schofield CJ | title = Fluoromethylated derivatives of carnitine biosynthesis intermediates - synthesis and applications | journal = Chem. Commun. | volume = 50 | issue = 10 | pages = 1175–1177 |date=February 2014 | pmid = 24317009 | doi = 10.1039/c3cc47581f | doi-access = free }} biological mass spectrometry,{{Cite journal|last1=Mecinović|first1=Jasmin|last2=Chowdhury|first2=Rasheduzzaman|last3=Flashman|first3=Emily|last4=Schofield|first4=Christopher J.|date=15 October 2009|title=Use of mass spectrometry to probe the nucleophilicity of cysteinyl residues of prolyl hydroxylase domain 2|journal=Analytical Biochemistry|volume=393|issue=2|pages=215–221|doi=10.1016/j.ab.2009.06.029|pmid=19563769}} molecular biology,{{Cite journal|last1=Tan|first1=SuatCheng|last2=Carr|first2=CarolynA.|last3=Yeoh|first3=KarKheng|last4=Schofield|first4=ChristopherJ.|last5=Davies|first5=KayE.|last6=Clarke|first6=Kieran|date=1 April 2012|title=Identification of valid housekeeping genes for quantitative RT-PCR analysis of cardiosphere-derived cells preconditioned under hypoxia or with prolyl-4-hydroxylase inhibitors|journal=Molecular Biology Reports|volume=39|issue=4|pages=4857–4867|doi=10.1007/s11033-011-1281-5|issn=0301-4851|pmc=3294216|pmid=22065248}} enzyme kinetics,{{cite journal |vauthors=Rydzik AM, Leung IK, Kochan GT, Thalhammer A, Oppermann U, Claridge TD, Schofield CJ | title = Development and application of a fluoride-detection-based fluorescence assay for γ-butyrobetaine hydroxylase | journal = ChemBioChem | volume = 13 | issue = 11 | pages = 1559–1563 |date=July 2012 | pmid = 22730246 | doi = 10.1002/cbic.201200256 | s2cid = 13956474 }}{{Cite journal|last1=Flashman|first1=Emily|last2=Bagg|first2=Eleanor A. L.|last3=Chowdhury|first3=Rasheduzzaman|last4=Mecinović|first4=Jasmin|last5=Loenarz|first5=Christoph|last6=McDonough|first6=Michael A.|last7=Hewitson|first7=Kirsty S.|last8=Schofield|first8=Christopher J.|date=15 February 2008|title=Kinetic Rationale for Selectivity toward N- and C-terminal Oxygen-dependent Degradation Domain Substrates Mediated by a Loop Region of Hypoxia-Inducible Factor Prolyl Hydroxylases|journal=Journal of Biological Chemistry|language=en|volume=283|issue=7|pages=3808–3815|doi=10.1074/jbc.M707411200|issn=0021-9258|pmid=18063574|doi-access=free}} protein-directed dynamic combinatorial chemistry{{cite journal |vauthors=Demetriades M, Leung IK, Chowdhury R, Chan MC, McDonough MA, Yeoh KK, Tian YM, Claridge TD, Ratcliffe PJ, Woon EC, Schofield CJ | title = Dynamic combinatorial chemistry employing boronic acids/boronate esters leads to potent oxygenase inhibitors | journal = Angew. Chem. Int. Ed. | volume = 51 | issue = 27 | pages = 6672–6675 |date=July 2012 | pmid = 22639232 | doi = 10.1002/anie.201202000 }}{{cite journal |vauthors=Leung IK, Brown T Jr, Schofield CJ, Claridge TD | title = An approach to enzyme inhibition employing reversible boronate ester formation | journal = Med. Chem. Commun. | volume = 2 | issue = 5 | pages = 390–395 |date=March 2011 | doi = 10.1039/C1MD00011J }} and organic synthesis/medicinal chemistry.{{Cite journal|last1=Chan|first1=Mun Chiang|last2=Atasoylu|first2=Onur|last3=Hodson|first3=Emma|last4=Tumber|first4=Anthony|last5=Leung|first5=Ivanhoe K. H.|last6=Chowdhury|first6=Rasheduzzaman|last7=Gómez-Pérez|first7=Verónica|last8=Demetriades|first8=Marina|last9=Rydzik|first9=Anna M.|date=6 July 2015|title=Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain|journal=PLOS ONE|volume=10|issue=7|pages=e0132004|doi=10.1371/journal.pone.0132004|issn=1932-6203|pmc=4492579|pmid=26147748|bibcode=2015PLoSO..1032004C|doi-access=free}}{{Cite journal|last1=Thinnes|first1=C. C.|last2=Tumber|first2=A.|last3=Yapp|first3=C.|last4=Scozzafava|first4=G.|last5=Yeh|first5=T.|last6=Chan|first6=M. C.|last7=Tran|first7=T. A.|last8=Hsu|first8=K.|last9=Tarhonskaya|first9=H.|date=8 October 2015|title=Betti reaction enables efficient synthesis of 8-hydroxyquinoline inhibitors of 2-oxoglutarate oxygenases|journal=Chemical Communications|language=en|volume=51|issue=84|doi=10.1039/C5CC06095H|pmid=26345662|issn=1364-548X|pages=15458–15461}}

Most clinically used antibiotics are based upon natural products. The most important family of antibiotics contains a β-lactam ring, and includes the penicillin,{{Cite journal|last1=van Berkel|first1=Sander S.|last2=Nettleship|first2=Joanne E.|last3=Leung|first3=Ivanhoe K. H.|last4=Brem|first4=Jürgen|last5=Choi|first5=Hwanho|last6=Stuart|first6=David I.|last7=Claridge|first7=Timothy D. W.|last8=McDonough|first8=Michael A.|last9=Owens|first9=Raymond J.|date=15 August 2013|title=Binding of (5 S )-Penicilloic Acid to Penicillin Binding Protein 3|journal=ACS Chemical Biology|language=EN|volume=8|issue=10|pages=2112–2116|doi=10.1021/cb400200h|pmid=23899657}} cephalosporin, clavam,{{Cite journal|last1=MacKenzie|first1=Alasdair K.|last2=Kershaw|first2=Nadia J.|last3=Hernandez|first3=Helena|last4=Robinson|first4=Carol V.|last5=Schofield|first5=Christopher J.|last6=Andersson|first6=Inger|date=19 January 2007|title=Clavulanic Acid Dehydrogenase: Structural and Biochemical Analysis of the Final Step in the Biosynthesis of the β-Lactamase Inhibitor Clavulanic Acid † , ‡|journal=Biochemistry|language=en|volume=46|issue=6|pages=1523–1533|doi=10.1021/bi061978x|pmid=17279617}} and carbapenem{{Cite journal|last1=Borowski|first1=Tomasz|last2=Broclawik|first2=Ewa|last3=Schofield|first3=Christopher J.|last4=Siegbahn|first4=Per E. M.|date=30 April 2006|title=Epimerization and desaturation by carbapenem synthase (CarC). A hybrid DFT study|journal=Journal of Computational Chemistry|language=en|volume=27|issue=6|pages=740–748|doi=10.1002/jcc.20384|pmid=16521121|s2cid=21775977|issn=1096-987X|doi-access=free}} antibiotics. The group's biosynthetic work has focused on the clavams{{Cite journal|last1=Mackenzie|first1=Alasdair K.|last2=Valegård|first2=Karin|last3=Iqbal|first3=Aman|last4=Caines|first4=Matthew E. C.|last5=Kershaw|first5=Nadia J.|last6=Jensen|first6=Susan E.|last7=Schofield|first7=Christopher J.|last8=Andersson|first8=Inger|date=19 February 2010|title=Crystal Structures of an Oligopeptide-Binding Protein from the Biosynthetic Pathway of the β-Lactamase Inhibitor Clavulanic Acid|journal=Journal of Molecular Biology|volume=396|issue=2|pages=332–344|doi=10.1016/j.jmb.2009.11.045|pmid=19941870}} and carbapenems, with a particular focus being on the mechanism and structures of enzymes that catalyse chemically 'interesting' steps.{{Cite journal|last1=Long|first1=Alexandra J.|last2=Clifton|first2=Ian J.|last3=Roach|first3=Peter L.|last4=Baldwin|first4=Jack E.|last5=Schofield|first5=Christopher J.|last6=Rutledge|first6=Peter J.|date=15 June 2003|title=Structural studies on the reaction of isopenicillin N synthase with the substrate analogue delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-alpha-aminobutyrate|journal=Biochemical Journal|language=en|volume=372|issue=3|pages=687–693|doi=10.1042/bj20021627|issn=0264-6021|pmid=12622704|pmc=1223433}}{{Cite journal|last1=Sleeman|first1=Mark C|last2=MacKinnon|first2=Colin H|last3=Hewitson|first3=Kirsty S|last4=Schofield|first4=Christopher J|date=25 February 2002|title=Enzymatic Synthesis of Monocyclic β-Lactams|journal=Bioorganic & Medicinal Chemistry Letters|volume=12|issue=4|pages=597–599|doi=10.1016/S0960-894X(01)00806-X|pmid=11844680}} The biggest threat to the continued use of β-lactam antibiotics is that of bacterial resistance. Schofield is currently working on the design and synthesis of enzyme inhibitors{{Cite journal|last1=Liénard|first1=Benoît M. R.|last2=Hüting|first2=Rebekka|last3=Lassaux|first3=Patricia|last4=Galleni|first4=Moreno|last5=Frère|first5=Jean-Marie|last6=Schofield|first6=Christopher J.|date=19 January 2008|title=Dynamic Combinatorial Mass Spectrometry Leads to Metallo-β-lactamase Inhibitors|journal=Journal of Medicinal Chemistry|language=EN|volume=51|issue=3|pages=684–688|doi=10.1021/jm070866g|pmid=18205296}}{{Cite journal|last1=Brem|first1=Jürgen|last2=Berkel|first2=Sander S. van|last3=Zollman|first3=David|last4=Lee|first4=Sook Y.|last5=Gileadi|first5=Opher|last6=McHugh|first6=Peter J.|last7=Walsh|first7=Timothy R.|last8=McDonough|first8=Michael A.|last9=Schofield|first9=Christopher J.|date=1 January 2016|title=Structural Basis of Metallo-β-Lactamase Inhibition by Captopril Stereoisomers|journal=Antimicrobial Agents and Chemotherapy|language=en|volume=60|issue=1|pages=142–150|doi=10.1128/AAC.01335-15|issn=0066-4804|pmc=4704194|pmid=26482303}}{{Cite journal|last1=Liénard|first1=Benoît M. R.|last2=Horsfall|first2=Louise E.|last3=Galleni|first3=Moreno|last4=Frère|first4=Jean-Marie|last5=Schofield|first5=Christopher J.|date=15 February 2007|title=Inhibitors of the FEZ-1 metallo-β-lactamase|journal=Bioorganic & Medicinal Chemistry Letters|volume=17|issue=4|pages=964–968|doi=10.1016/j.bmcl.2006.11.053|pmid=17157014}}{{Cite journal|last1=Brem|first1=Jürgen|last2=Cain|first2=Ricky|last3=Cahill|first3=Samuel|last4=McDonough|first4=Michael A.|last5=Clifton|first5=Ian J.|last6=Jiménez-Castellanos|first6=Juan-Carlos|last7=Avison|first7=Matthew B.|last8=Spencer|first8=James|last9=Fishwick|first9=Colin W. G.|date=8 August 2016|title=Structural basis of metallo-β-lactamase, serine-β-lactamase and penicillin-binding protein inhibition by cyclic boronates|journal=Nature Communications|language=en|volume=7|pages=12406|doi=10.1038/ncomms12406|pmid=27499424|pmc=4979060|bibcode=2016NatCo...712406B}} for the metallo β-lactamases{{Cite journal|last1=Makena|first1=Anne|last2=Düzgün|first2=Azer Ö|last3=Brem|first3=Jürgen|last4=McDonough|first4=Michael A.|last5=Rydzik|first5=Anna M.|last6=Abboud|first6=Martine I.|last7=Saral|first7=Ayşegül|last8=Çiçek|first8=Ayşegül Ç|last9=Sandalli|first9=Cemal|date=1 March 2016|title=Comparison of Verona Integron-Borne Metallo-β-Lactamase (VIM) Variants Reveals Differences in Stability and Inhibition Profiles|journal=Antimicrobial Agents and Chemotherapy|language=en|volume=60|issue=3|pages=1377–1384|doi=10.1128/AAC.01768-15|issn=0066-4804|pmc=4775916|pmid=26666919}} – there are no clinically used inhibitor{{Cite journal|last1=Abboud|first1=Martine I.|last2=Damblon|first2=Christian|last3=Brem|first3=Jürgen|last4=Smargiasso|first4=Nicolas|last5=Mercuri|first5=Paola|last6=Gilbert|first6=Bernard|last7=Rydzik|first7=Anna M.|last8=Claridge|first8=Timothy D. W.|last9=Schofield|first9=Christopher J.|date=11 July 2016|title=Interaction of Avibactam with Class B Metallo-β-lactamases|journal=Antimicrobial Agents and Chemotherapy|language=en|pages=AAC.00897–16|doi=10.1128/AAC.00897-16|issn=0066-4804|pmid=27401561|volume=60|issue=10|pmc=5038302}} of these enzymes but they pose a significant threat as they catalyse the hydrolysis of almost all clinically used β-lactam antibiotics.{{Cite journal|last1=Makena|first1=Anne|last2=Brem|first2=Jürgen|last3=Pfeffer|first3=Inga|last4=Geffen|first4=Rebecca E. J.|last5=Wilkins|first5=Sarah E.|last6=Tarhonskaya|first6=Hanna|last7=Flashman|first7=Emily|last8=Phee|first8=Lynette M.|last9=Wareham|first9=David W.|date=1 February 2015|title=Biochemical characterization of New Delhi metallo-β-lactamase variants reveals differences in protein stability|journal=Journal of Antimicrobial Chemotherapy|language=en|volume=70|issue=2|pages=463–469|doi=10.1093/jac/dku403|issn=0305-7453|pmc=4291237|pmid=25324420}} A particular interest involves human metallo β-lactamases which share the same fold.{{Cite journal|last1=Pettinati|first1=Ilaria|last2=Brem|first2=Jürgen|last3=McDonough|first3=Michael A.|last4=Schofield|first4=Christopher J.|date=1 May 2015|title=Crystal structure of human persulfide dioxygenase: structural basis of ethylmalonic encephalopathy|journal=Human Molecular Genetics|language=en|volume=24|issue=9|pages=2458–2469|doi=10.1093/hmg/ddv007|issn=0964-6906|pmc=4383860|pmid=25596185}}

2015-2020: Wellcome Trust Advanced Investigator Award (with Sir Peter Ratcliffe)

2013: Fellow of the Royal Society (London); Member of EMBO; Fellow of the Royal Society of Biology, UK; Member of the Biochemical Society; Member of the Society for Experimental Biology, UK

2012: Finalist – Biotechnology and Biological Sciences Research Council 'Innovator of the Year'{{Cite web|url=http://www.bbsrc.ac.uk/about/governance-structure/panels/research-panel/|title=Research Advisory Panel – BBSRC|last=Council|first=Biotechnology and Biological Sciences Research|website=bbsrc.ac.uk|language=en|access-date=2017-02-25}}

2011: Royal Society of Chemistry, Jeremy Knowles Award, UK;{{Cite web|url=http://www.rsc.org/ScienceAndTechnology/Awards/JeremyKnowlesAward/2011winner.asp|title=Jeremy Knowles Award 2011 Winner|publisher=rsc.org|access-date=2017-02-25}} Highly cited paper awards (e.g. Biochemical Journal, Bioorganic & Medicinal Chemistry Letters)

2009 – 2014: PI of ERC Advanced Investigator Grant SPA GA 2008 233240 (with Sir Peter Ratcliffe); Molecular Mechanism of Oxygen Sensing by Enzymes (MOOSE)

2000: Fellow of the Royal Society of Chemistry (London)

{{Reflist}}

• http://schofield.chem.ox.ac.uk/
• http://research.chem.ox.ac.uk/christopher-schofield.aspx

{{Authority control}}

{{DEFAULTSORT:Schofield, Christopher J.}}

Category:1960 births

Category:Alumni of St John's College, Oxford

Category:Alumni of the University of Manchester Institute of Science and Technology

Category:British chemists

Category:Fellows of Hertford College, Oxford

Category:Fellows of the Royal Society

Category:Fellows of the Royal Society of Chemistry

Category:People educated at St. Anselm's College

Category:Living people