Lakhal-Littleton Group

01865272543
samira.lakhal-littleton@dpag.ox.ac.uk

Iron and pathophysiology: From basic mechanisms to clinical translation

Mechanistic links between iron deficiency and heart failure

our research

Unique biochemical properties underpin the essential functions of iron in oxygen transport and oxidative phosphorylation. Those same properties also underpin its propensity to participate in Fenton-type reactions, producing cell-damaging reactive oxygen species. Thus, tight control of iron levels within tissues is paramount for normal physiological function, particularly in tissues of high oxygen demand/flux.

Our research focusses on understanding the impact of too little or too much iron on the cardiovascular system, and on translating that understanding into better management of iron status in cardiovascular disorders. Examples of our recent translational work include:

Discovering the impact of intravenous iron therapies on iron levels in different tissues

Vera-Aviles, M., Kabir, S. N., Shah, A., Polzella, P., Lim, D. Y., Buckley, P., Ball, C., Swinkels, D., Matlung, H., Blans, C., Holdship, P., Nugent, J., Anderson, E., Desborough, M., Piechnik, S., Ferreira, V., & Lakhal-Littleton, S✉. (2024). Intravenous iron therapy results in rapid and sustained rise in myocardial iron content through a novel pathway. European heart journal, 45(42), 4497–4508. https://doi.org/10.1093/eurheartj/ehae359 *This work was highlighted in a special issue by the editor https://doi.org/10.1093/eurheartj/ehae752 and an accompanying editorial was invited https://doi.org/10.1093/eurheartj/ehae560.
Piechnik, S. K., Polzella, P., Shah, A., Vera-Aviles, M., Kabir, S. N., Desborough, M., Ferreira, V. M., & Lakhal-Littleton, S✉. (2025). Myocardial iron intake following intravenous iron therapy with ferric carboxymaltose is sustained at 1 year despite recurrence of iron deficiency. British journal of haematology, 206(1), 349–352. https://doi.org/10.1111/bjh.19915

Placing basic discoveries into clinical context;

Lakhal-Littleton, S✉., & Cleland, J. G. F. (2024). Iron deficiency and supplementation in heart failure. Nature reviews. Cardiology, 21(7), 463–486. https://doi.org/10.1038/s41569-024-00988-1
Lakhal-Littleton S✉. (2025). Anaemia, neurohormonal activation, and myocardial iron depletion in heart failure: can this vicious circle be broken?. European heart journal, 46(16), 1524–1527. https://doi.org/10.1093/eurheartj/ehae798
Lakhal-Littleton, S✉., (2025) Iron deficiency in heart failure. Iron in Clinical Practice. edited by Sue Pavord and Noemi Roy. ISBN: 978-1-394-21090-9. https://www.wiley.com/en-us/Iron+in+Clinical+Practice-p-9781394210909
Cleland, J. G. F., Pellicori, P., & Lakhal-Littleton, S. (2024). Low Serum Ferritin Might Predict Incident Heart Failure: But Why and Is It Clinically Useful?. JACC. Heart failure, 12(3), 549–551. https://doi.org/10.1016/j.jchf.2023.12.01

Revealing the impact of inflammation on spleen iron trapping after intravenous iron therapy

Nunez, J., Mollar, A., Vera-Aviles, M., Kabir, S., Shah, A., Polzella, P., Desborough, M., Cardells, I., Miñana, G., Del Canto, I., Ferreira, V., Piechnik, S., Maceira, A., & Lakhal-Littleton, S✉. (2025). Baseline serum ferritin predicts myocardial iron uptake following intravenous iron therapy - a hypothesis-generating study. European journal of heart failure, 10.1002/ejhf.3730. Advance online publication. https://doi.org/10.1002/ejhf.3730

Mechanistically defining the impact of iron status on long-term outcomes of myocardial infarction

Vera-Aviles, M., Kabir, S.N., Christodoulou, M.D., Shanmuganathan, M., Kotronias, R., Cleland, J.G.F., OxAMI investigators, Channon, K.M., Lakhal-Littleton, S✉.(2025) Hypoferremia reduces long-term risk of major adverse cardiovascular events after STEMI by averting the myocardial reactive iron storm. medRxiv 2025.01.13.25320244; doi: https://doi.org/10.1101/2025.01.13.25320244

Our team

Samira Lakhal-Littleton

MRC Senior Non-Clinical Research Fellow, Principal Investigator, Professor of Cell Physiology and Tutorial Fellow in Medicine
Mayra Vera-Aviles

Postdoctoral Research Scientist
Charlotte Ball

DPhil Student
Zepeng Cao

DPhil Student
Dillon Lim

DPhil Student
Poppy Buckley

Biomedical Sciences Part C (Masters) Student
Syeeda Kabir

Postdoctoral Research Scientist
Dean Chaumoo

FHS Student
Abdalrahman Alabdallah