Alan Stewart Group – Metal ions in Medicine
Group Highlights
Our work is centred on how metal ions, such as Zn2+, Ca2+ and Co2+ are transported through the blood and how their mishandling can lead to disease. A key part of my group’s activity is the study of their interactions with circulatory proteins. At a cell and systems level, we are interested in how these interactions have a functional impact. We commonly utilise methods that examine the movement of Zn2+ and Ca2+ ions within cells and across membranes or measure their direct physiological functional outputs (e.g. coagulatory processes). Over the last few years, we have also worked closely with colleagues across the North Haugh particularly, the Mass Spectrometry Facility in St Andrews in the utilisation of quantitative proteomics clinical studies.
Please visit our group website: https://metalion.wp.st-andrews.ac.uk/
Effects of fatty acid binding at the FA2 site on the primary zinc site of human serum albumin. (A) Structure of HSA with 5 molecules of myristate bound (PDB: 1BJ5). (B) Overlay of the main zinc-binding site in the myristate-bound structure (in green; PDB: 1BJ5) and the zinc-bound structure (in blue; PDB: 5IJF). A structural change is induced by fatty acid binding. This triggers the zinc-coordinating residue His67 to move 8 Å away from the other two coordinating side chains. Figure taken from Sobczak et al. (2021) Chem. Sci. 12: 4079-4093.
Research
Bilateral BBSRC-FAPESP: A “speciomic” toolkit to investigate fatty acid-mediated changes in plasma zinc speciation and their physiological effects.
Tenovus Scotland: Assessment of the predictive value of plasma proteins in oesophageal adenocarcinoma treatment
British Heart Foundation: Plasma non-esterified fatty acids and fibrin clot formation in obesity – a relationship forged in zinc?
British Heart Foundation: Role of plasma fatty acid and zinc dynamics in platelet functioning: Implications for pathological clotting
Group Members
Dr Remi Fritzen; Research Fellow
Dongmei Wu; PhD student
Jordan Marsh; PhD student
Stephen Hierons; PhD student
Hasnain Ahmed; PhD student
Amy Davies; Visiting Scholar
Publications
Chapters
Exploring ICP-MS as a versatile technique: from imaging to chemical speciation analysis
Amais, R. S., de Andrade, A. M., Santos da Silva, A. B., Freitas, D. C., Francischini, D. D. S., Stewart, A. J. & Arruda, M. A. Z., 24 May 2022, ICP-MS and trace element analysis as tools for better understanding medical conditions. Arruda, M. A. Z. & de Jesus, J. R. (eds.). Amsterdam: Elsevier, p. 141-177 37 p. (Comprehensive analytical chemistry; vol. 97).
Research output: Chapter in Book/Report/Conference proceeding › Chapter
The formation and Zn2+-dependence of histidine-rich glycoprotein-containing immune complexes.
Kassaar, O., Powis, S. J. & Stewart, A. J., Dec 2012, Advances in Medicine and Biology. Berhardt, L. V. (ed.). Nova Science Publishers, Vol. 58. p. 153-166 14 p.
Research output: Chapter in Book/Report/Conference proceeding › Chapter
Articles
Abnormal plasma/serum magnesium, copper and zinc concentrations associate with the future development of cardiovascular diseases
Lin, B., Alexander, R., Fritzen, R., Mills, S., Stewart, A. J. & McCowan, C., 25 Apr 2025, In: Nutrients. 17, 9, p. 1-14 14 p., 1447.
Research output: Contribution to journal › Article › peer-review
Investigating the conformational landscape of human histidine-rich glycoprotein using amide HDX-MS
Hierons, S. J., Lin, B., Fritzen, R., Blindauer, C. A., Ajjan, R. A., Masson, G. R. & Stewart, A. J., Nov 2025, In: Biochemical Journal. 482, 22, p. 1721-1735 15 p.
Research output: Contribution to journal › Article › peer-review
Properties of the major Zn2+-binding site of human alpha-fetoprotein, a potential foetal plasma zinc carrier
Lu, J., Hierons, S. J., Arya, S., Fritzen, R., Polepalli, S., Khazaipoul, S., Stewart, A. J. & Blindauer, C. A., 4 Feb 2025, In: Chemical Communications. 61, 10, p. 2099-2102 4 p.
Research output: Contribution to journal › Article › peer-review
Quantitative proteomics identifies plasma protein alterations that associate with metabolic and thrombotic profile changes after bariatric surgery
Ahmed, H., Fernandes, M. F., Abbas, K., Synowsky, S. A., Shirran, S. L., Ajjan, R. A. & Stewart, A. J., May 2025, In: Diabetes, Obesity and Metabolism. 27, 5, p. 2647-2657 11 p.
Research output: Contribution to journal › Article › peer-review
Changes in fibrin clot properties in patients after Roux en-Y gastric bypass surgery
Abbas, K., Hierons, S. J., Pechlivani, N., Phoenix, F., Alexander, R., King, R., Ajjan, R. A. & Stewart, A. J., Feb 2024, In: Research and Practice in Thrombosis and Haemostasis. 8, 2, 8 p., e102361.
Research output: Contribution to journal › Article › peer-review
EPR spectroscopic characterisation of native CuII-binding sites in human serum albumin
Ackermann, K., Wu, D., Stewart, A. J. & Bode, B. E., 28 Aug 2024, In: Dalton Transactions. 53, 32, p. 13529-13536 8 p.
Research output: Contribution to journal › Article › peer-review
Metallomic analysis of urine from individuals with and without Covid-19 infection reveals extensive alterations in metal homeostasis
da Silva Leal, K. N., da Silva, A. B. S., Fonseca, E. K. B., de Oliveira Moreira, O. B., de Lemos, L. M., de Oliviera, M. A. L., Stewart, A. J. & Arruda, M. A. Z., Dec 2024, In: Journal of Trace Elements in Medicine and Biology. 86, 11 p., 127557.
Research output: Contribution to journal › Article › peer-review
Optimizing the performance of single-cell ICP-MS for Fe and Zn determination in human umbilical vascular endothelial cells
Leal, K. N. S., da Silva, A. B. S., Aragão, A. Z. B., Ramos, C. H. I., Stewart, A. J. & Arruda, M. A. Z., 1 Jul 2024, In: Microchemical Journal. 202, 10 p., 110696.
Research output: Contribution to journal › Article › peer-review
Recent advances in metalloproteomics
Coverdale, J. P. C., Polepalli, S., Arruda, M. A. Z., Santos Da Silva, A. B., Stewart, A. J. & Blindauer, C. A., 13 Jan 2024, In: Biomolecules. 14, 1, 31 p., 104.
Research output: Contribution to journal › Review article › peer-review
Targeted removal of the FA2 site on human albumin prevents fatty acid-mediated inhibition of Zn2+-binding
Wu, D., Hierons, S. J., Polepalli, S., Gucwa, M., Fritzen, R., Markiewicz, M., Sabín, J., Minor, W., Murzyn, K., Blindauer, C. A. & Stewart, A. J., 1 Jun 2024, In: Journal of Lipid Research. 65, 6, 12 p., 100560.
Research output: Contribution to journal › Article › peer-review
Other publications
FXR activation aids fibrinolysis: targeting PAI-1 in obesity
Stewart, A. J., 13 Nov 2025, In: Blood. 146, 20, p. 2381-2382 2 p.
Research output: Contribution to journal › Comment/debate › peer-review
The importance of understanding why the Co2+-binding ability of albumin is reduced in ischemia
Stewart, A. J. & Blindauer, C. A., Apr 2025, In: International Journal of Gynecology & Obstetrics. 169, 1, p. 441-442 2 p.
Research output: Contribution to journal › Letter › peer-review
Editorial: Insulin resistance and cardiovascular disease
Stewart, A. J., Tuncay, E., Pitt, S. J. & Rainbow, R. D., 4 Aug 2023, In: Frontiers in Endocrinology. 14, 3 p., 1266173.
Research output: Contribution to journal › Editorial › peer-review
Response to Qian and Colvin: zinc-mediated regulation of the cardiac ryanodine receptor occurs via multiple binding sites
Woodier, J., Rainbow, R. D., Stewart, A. J. & Pitt, S. J., 19 Feb 2016, In: Journal of Biological Chemistry. 291, 8, p. 4267
Research output: Contribution to journal › Letter › peer-review
The reduced Co2+-binding ability of ischaemia-modified albumin is unlikely to be because of oxidative modification of the N-terminus
Stewart, A. J. & Blindauer, C. A., Dec 2015, In: Liver International. 35, 12, p. 2622-2623 2 p.
Research output: Contribution to journal › Letter › peer-review
Albumin research in the 21st century
Peters Jr, T. & Stewart, A. J., Dec 2013, In: Biochimica et Biophysica Acta - General Subjects. 1830, 12, p. 5351-5353 3 p.
Research output: Contribution to journal › Editorial
Design of mutated forms of human serum albumin with altered metal binding characteristics for pharmacological or cell culture uses.
Berezenko, S. (Inventor), Sadler, P. J. (Inventor), Stewart, A. J. (Inventor), Blindauer, C. A. (Inventor) & Bunyan, K. E. (Inventor), 5 Feb 2004, IPC No. C07K 14/765 (2006.01), Patent No. WO/2004/011499
Research output: Patent
Contact
Dr Alan J. Stewart PhD FRSB FRSC
Reader in Molecular Medicine
School of Medicine
Medical and Biological Sciences Building
University of St Andrews
St Andrews
Fife, KY16 9TF
United Kingdom
E-mail: [email protected]
Tel: +44 (0)1334 463546
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