Research Guides

Department of Chemistry University of Oxford

Professor James McCullagh

Research in the McCullagh Group focusses on the application of mass spectrometry and separation science to solve complex chemical problems manifesting at the interface of chemistry with biology, medicine and the environment. Our research centres around the comprehensive identification and quantification of small molecules in complex systems (chemical profiling) which includes biomarker discovery and targeted quantitiation with particular focus on disease processes. We also use stable isotope tracer techniques to understand the origin of compounds and carbon flow in natural and synthetic systems. This leads to a diverse range of applications which have included a project with the wine industry to identify chemical biomarkers associated with grape variety and geographic origin. We also have a long running collaboration with the Research Lab for Archaeology in Oxford which focusses on the discovery of chemical biomarkers of prehistoric diet.

Our main area of focus however is the development and applicaiton of metabolic profiling to understand changes in metabolism in pathology and disease processes. Projects currently include changes in metabolism associated with cancers expressing isocitrate dehydrogenase (IDH) mutations. These mutations produce high levels of 2-hydroxyglutate but the biological importance of these  mutations, within the context of tumour development, is not well understood. We are also interested in altered metabolism in Cardiovascular Disease, Diabetes  and are currently working with the ME association to investigate metabolic changes associated with chronic fatigue syndrome (ME/CFS).

We collaborate with a wide range of researchers in both academia and industry and have regular D.Phil. and Part II students in the group. Please contact Prof. James McCullagh discuss ideas for projects and collaboration. 

Chiara Bardella, Osama Al-Dalahmah, Daniel Krell, Pijus Brazauskas, Khalid Al-Qahtani, Marketa Tomkova, Julie Adam, Sébastien Serres, Helen Lockstone, Luke Freeman-Mills, Inga Pfeffer, Nicola Sibson, Robert Goldin, Benjamin Schuster-Böeckler, Patrick J. Pollard, Tomoyoshi Soga, James S. McCullagh, Christopher J. Schofield, Paul Mulholland, Olaf Ansorge, Skirmantas Kriaucionis, Peter J. Ratcliffe, Francis G. Szele, Ian Tomlinson. Expression of Idh1R132H in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis. Cell,  2016, Volume 30, Issue 4, p578–594.

Emir U, Larkin S, de Pennington N, Voets N, Plaha P, Stacey R, Al-Qahtani K,  Mccullagh J,  Schofield C, Clare S,  Jezzard P, Cadoux-Hudson T & Ansorge O. Non-invasive quantification of 2-hydroxyglutarate in human gliomas with IDH1 and IDH2 mutations. Cancer Research 2016, 1;76)1):43-9.

Uche FI, Drijfhout FP, McCullagh J, Richardson A, Li WW. Cytotoxicity Effects and Apoptosis Induction by Bisbenzylisoquinoline Alkaloids from Triclisia subcordata. Phytother Res. 2016; 30(9):1533-9.

Anthony H. Lynch, N. Kruger, Robert E.M. Hedges and James S.O. McCullagh* Variability in the 13C/12C isotope ratios of individual amino acids in plant proteins. Phytochemistry 2016, Vol 125; pp27-34.

Adam Berrington, Natalie L. Voets, Puneet Plaha, Sarah J. Larkin, James Mccullagh, Richard Stacey, Muhammed Yildirim, Christopher J. Schofield, Peter Jezzard, Tom Cadoux-Hudson, Olaf Ansorge, and Uzay E. Emir. Improved Localization for 2-Hydroxyglutarate Detection at 3 T Using Long-TE Semi-LASER. Tomography, 2016, Vol2; (2), p94.

Tarhonskaya H, Hardy AP, Howe EA, Loik ND, Kramer HB, McCullagh JS, Schofield CJ, Flashman E. Kinetic Investigations of the Role of Factor Inhibiting Hypoxia-inducible Factor (FIH) as an Oxygen Sensor. The Journal of Biological Chemistry 290 (32):19726-19742 Aug 2015.

Al-Qahtani K,  Jabeen B, Sekirnik R, Riaz N, D.W. Claridge T, J. Schofield C, and. McCullagh J* The Broad Spectrum 2-Oxoglutarate Oxygenase Inhibitor N-oxalylglycine is present in Rhubarb and Spinach Leaves. 2014. Phytochemistry, Sept 2015. 117:456-461.

Valli A, Rodriguez M, Moutsianas L, Fischer R,Fedele V, Huang H, Van Stiphout R, Jones D1, Mccarthy M, Vinaixa M, Igarashi K, Sato M, Soga T, Buffa F, Mccullagh J, Yanes O, Harris AL, and Kessler B. Hypoxia induces a HIF1α-dependent lipogenic phenotype in colorectal cancer cells. 2014. Oncotarget 2015;10;6(4):1920‐41.

Anthony H. Lynch, N. Kruger, Robert E.M. Hedges and James S.O. McCullagh.* Variability in the 13C/12C isotope ratios of individual amino acids in plant proteins. 2014. Under review: Phytochemistry.

Tarhonskaya H, Chowdhury R, Leung IK, Loik ND, McCullagh JS, Claridge TD, Schofield CJ, Flashman E. Investigating the contribution of the active site environment to the slow reaction of hypoxia-inducible factor prolyl hydroxylase domain 2 with oxygen. The Biochemical journal. 2014; 463(3):363-372 Nov 2014.

Rachel Schiller, Dr. Giuseppe Scozzafava, Dr. Anthony Tumber, Dr. James R. Wickens, Jacob T. Bush, Dr. Ganesha Rai, Dr. Clarisse Lejeune, Dr. Hwanho Choi, Dr. Tzu-Lan Yeh, Mun Chiang Chan, Dr. Bryan T. Mott, Dr. James S. O. McCullagh, Dr. David J. Maloney, Prof. Christopher J. Schofield, Dr. Akane Kawamura. A Cell-Permeable Ester Derivative of the JmjC Histone Demethylase Inhibitor IOX1. ChemMedChem. DOI: 10.1002/cmdc.201300428.

Gong L, McCullagh JSO*. Comparing ion-pairing reagents and sample dissolution solvents for ion-pairing reversed-phase liquid chromatography/electrospray ionization mass spectrometry analysis of oligonucleotides. Rapid Communications in Mass Spectrometry 28 (4):339-350 28 Feb 2014.

Tianshu Feng, Atsushi Yamamoto, Sarah E Wilkins, Elizaveta Sokolova, Luke A Yates, Martin Münzel, Pooja Singh, Richard J Hopkinson, Roman Fischer, Matthew E Cockman, Jake Shelley, David C Trudgian, Johannes Schödel, James S O McCullagh, Wei Ge, Benedikt M Kessler, Robert J Gilbert, Ludmila Y Frolova, Elena Alkalaeva, Peter J Ratcliffe, Christopher J Schofield, Mathew L Coleman. Optimal Translational Termination Requires C4 Lysyl Hydroxylation of eRF1. Molecular cell. 2014, 20;53(4):645-54

Feng T, Yamamoto A, Wilkins SE, Sokolova E, Yates LA, Münzel M, Singh P, Hopkinson RJ, Fischer R, Cockman ME, et al. Optimal translational termination requires C4 lysyl hydroxylation of eRF1. Molecular cell 2014, 53(4):645-654.

Chooi KP, Galan SR, Raj R, McCullagh J, Mohammed S, Jones LH, Davis BG. Synthetic phosphorylation of p38α recapitulates protein kinase activity. Journal of the American Chemical Society, 2014, 136(5):1698-1701.

Tarhonskaya H, Rydzik AM, Leung IK, Loik ND, Chan MC, Kawamura A, McCullagh JS, Claridge TD, Flashman E, Schofield CJ. Non-enzymatic chemistry enables 2-hydroxyglutarate-mediated activation of 2-oxoglutarate oxygenases. Nature communications 2014, 5:3423.

Nalawade-Chavan S, McCullagh J, Hedges R. New hydroxyproline radiocarbon dates from Sungir, Russia, confirm early mid upper palaeolithic burials in Eurasia. PLoS One 2014; 9 (1):e76896

Nalawade-Chavan S, Hedges R, Ramsey CB, Higham T, McCullagh J, Bonsall C, Boroneanţ A. Compound-specific radiocarbon dating of essential and nonessential amino acids: Towards determination of dietary reservoir effects in humans. Radiocarbon, 2013, 55(2-3):709-719.

Anat Marom, James S O McCullagh, Thomas F G Higham, Robert E M Hedges. Hydroxyproline dating: Experiments on the 14C analysis of contaminated and low collagen bones. RADIOCARBON, Vol 55, Nr 2–3, 2013, p 698–708

Yang M, Hardy AP, Chowdhury R, Loik ND, Scotti JS, McCullagh JS, Claridge TD, McDonough MA, Ge W, Schofield CJ. Substrate Selectivity Analyses of Factor Inhibiting Hypoxia-Inducible Factor. Angew Chem Int Ed Engl. 2013.

Elena M Sanchez-Fernandez, Hanna Tarhonskaya, Khalid Al Qahtani, Richard J Hopkinson, James S.O. McCullagh, Christopher J Schofield, Emily Flashman. Investigations on the Oxygen Dependence of a 2-Oxoglutarate Histone Demethylase. Biochemical Journal. 2013; 449, 491-6.

Marom A, Higham TFG, Sinitsyn AA, REM HedgesMcCullagh JSO.* Single amino acid radiocarbon dating of Upper Palaeolithic modern humans. Proceedings of the National Academy of Sciences. 18th April 2012.

Mantri M, Webby CJ, Loik ND, Hamed RB, Nielsen ML, McDonough MA, McCullagh JSO, Boettger A, Schofield CJ, Wolf A. Self-hydroxylation of the splicing factor lysyl hydroxylase, JMJD6. MedChemComm 2012, 3(1):80-85.

Tripp JA and McCullagh JS. Preparative HPLC separation of underivatized amino acids for isotopic analysis. 828: 339-350. In Method in Molecular Biology Series 828: Amino acid analysis, eds Alterman MA and Hunziker P. Springer 2012.

Wei Ge, Alexander Wolf, Tianshu Feng, Chia-hua Ho, Rok Sekirnik, Adam Zayer, Nicolas Granatino, Matthew E. Cockman , Christoph Loenarz1 , Nikita D.Loik , Adam P. Hardy , Timothy D.W. Claridge, Mukram M. Mackeen, James S. Mccullagh, Yuliya Gordiyenko, Armin Thalhammer, Atsushi Yamamoto, Ming Yang, Yi Liu, Zhihong Zhang, Marion Schmidt-Zachmann, Benedikt M. Kessler, Peter J. Ratcliffe, Gail M. Preston, Mathew L. Coleman and Christopher J. Schofield. Oxygenase catalysed Ribosome Hydroxylation is conserved from Prokaryotes to Humans. Nature Chemical Biology. 2012; 8, 960-2.

Sanchez-Fernandez EM, Tarhonskaya H, Al-Qahtani K, Hopkinson J, McCullagh JSO, Candela-Lena JI, Schofield CJ, Flashman E. Kinetic investigations on the reaction of a 2-oxoglutarate dependent histone demethylase with oxygen. FEBS JOURNAL. 2012, 279:478-478.

Honch NV, McCullagh JS, Hedges REM. Variation of bone collagen amino acid δ13C values in archaeological humans and fauna with different dietary regimes: developing frameworks of dietary discrimination. Am. J. Phys. Anthropol. 2012; 148 (4): 495-511.

Jean-Philippe Godin & James S. O. McCullagh.* Current applications and challenges for liquid chromatography coupled to isotope ratio mass spectrometry (LC/IRMS). Rapid Communications in Mass Spectrometry. 2011, 25, 3019–3028.

Anthony H. Lynch, James S. O. McCullagh*, and Robert E. M. Hedges. Liquid chromatography/isotope ratio mass spectrometry measurement of δ13C of amino acids in plant proteins. Rapid Communications in Mass Spectrometry. 2011, 25, 2981–2988.

A.M. Pollard, P. Ditchfield, J.S.O. McCullagh, T.G. Allen, M. Gibson, C. Boston, S. Clough, N. Marquez-Grant, and R.A. Nicholson. ‘‘These Boots Were Made For Walking’’: The Isotopic Analysis of a C4 Roman Inhumation From Gravesend, Kent, UK. Amercian Journal of Physical Anthropology. (2011): 146:446–456.

McCullagh J*, Godin JP, Schierbeek H, Preston T. Liquid Chromatography-Isotope Ratio Mass Spectrometry Review. Rapid communications in mass spectrometry, 2011, 25(20):2969-2970.

Lingzhi Gong and James S.O. McCullagh.* Analysis of oligonucleotides by hydrophilic interaction liquid chromatography coupled to negative ion electrospray ionization mass spectrometry. Journal of Chromatography A, 1218 (2011) 5480-5486.

Gaye-Siessegger, Focken, U. J., McCullagh J.S.O.* The effect of dietary amino acid abundance and isotopic composition on the growth rate, metabolism and tissue d13C of rainbow trout. British Journal of Nutrition (2011), doi:10.1017/S0007114510005696

McCullagh J.S.O.*, (2010) Mixed mode chromatography isotope ratio mass spectrometry. Rapid Communications in Mass Spectrometry. (2010) 24; 483-494.

Monica Mantri, Nikita D. Loik, Refaat B. Hamed, Timothy D. W. Claridge, James S. O. McCullagh, Christopher J. Schofield. The 2-Oxoglutarate Dependent Oxygenase JMJD6 Catalyses Oxidation of Lysine Residues to give 5S-Hydroxylysine Residues. ChemBioChem, (2011), 12, 531-534.

McCullagh J.S.O, Marom A and Hedges R.E.M. Radiocarbon dating of individual amino acids from archaeological bone collagen. Radiocarbon. vol 52, Nr 2-3, 2010, p 620-634.

Raghavan, M., McCullagh J.S.O and Hedges R.E.M. Amino acid δ13C analysis of hair keratin using liquid chromatography/isotope ratio mass spectrometry: Palaeodietary implications from intra-individual comparisons with bone collagen. Rapid Communications in Mass Spectrometry. (2010) 24; 541-548.

Schneider R, Jensen SA, Whitman P, McCullagh JSO, Redfield C and Handford PA. Biophysical Characterisation of Fibulin-5 Proteins Associated with Disease. J Mol Biol. 2010;401(4):605-17.

McCullagh J.S.O. Mass Spectrometry. Chapter 13 in ‘The organic Chemist’s Handbook’ (2nd edition).

James McCullagh, Julia Gaye-Siessegger and Ulfert Focken. Determination of underivatized amino acid d13C by liquid chromatography/isotope ratio mass spectrometry for nutritional studies: the effect of dietary non-essential amino acid profile on the isotopic signature of individual amino acids in fish. Rapid Commun. Mass Spectrom. 2008; 22: 1817–1822

McCullagh, J.S.O and Hedges REM. ‘The Spectrometry Handbook’. Invited contribution (Chapter 33: Mass Spectrometry in Archaeology).

McCullagh J.S.O. (2007) Isotopic Analysis at the Molecular Level: A Frontier in Palaeodietary Reconstruction. In Crossing Frontiers, OUP, Monograph, Oxford.

James S.O. McCullagh,* Dieter Juchelka and Robert E. M. Hedges. Analysis of amino acid 13C abundance from humanand faunal bone collagen using liquid chromatography/isotope ratio mass spectrometry. Rapid Commun. Mass Spectrom. 2006; 20: 2761–2768.

Tripp, J.A., McCullagh, J.S.O. and Hedges, R.E.M., Preparative separation of underivatized amino acids for compound-specific stable isotope analysis and radiocarbon dating of hydrolyzed bone collagen. Journal of Separation Science, (2006) 29(1), 41-48.

McCullagh, J.S.O., Tripp, J.A. and Hedges, R.E.M., Carbon isotope analysis of bulk keratin and single amino acids from British and North American hair. Rapid Communications in Mass Spectrometry, (2005) 19(22). 3227-3231.