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Samira Lakhal-Littleton
BSc DPhil
Associate Professor of Cell Physiology and MRC Senior Non-Clinical Research Fellow
- Principal Investigator
- Tutorial Fellow in Medicine Brasenose College Oxford
My research to date has revolved around nutrient homeostasis in cells and systems biology. In recent years, I developed a more specialised interest in iron homeostasis. In particular, I aim to understand how iron is controlled in various systems and the importance of such control for normal physiological function.
Following a degree in Human Genetics at University College London, I joined the University of Oxford in 2004 as a DPhil student in the laboratory of Prof Cerundolo at the Weatherall Institute of Molecular Medicine. At the time, I was interested in the role of amino acid metabolism in the regulation of immune responses and tumour immune surveillance. It was during that time, while working on a tryptophan-degrading enzyme that is iron-dependent, that I developed interest in iron homeostasis.
In 2007, I went on to undertake my first postdoctoral project in the laboratory of Prof Ratcliffe, focussing on the interplay between Hypoxia Inducible Factors (HIFs) and iron homeostasis. HIFs, master transcription factors whose function is regulated by both oxygen and iron levels, in turn regulate cellular and systemic iron levels. My research findings defined some of the molecular mechanisms underlying the relationship between HIFs, hypoxia and iron homeostasis, e.g I discovered that the iron regulatory genes TMPRSS6 and GDF15 are both responsive to hypoxia. I also collaborated with human physiologists in a bid to understand how the major iron regulatory hormone hepcidin is regulated by altitude hypoxia and iron status. TMPRSS6, GDF15 and Hepcidin are all implicated in diseases of deregulated iron metabolism.
Following a period of maternity leave, I returned to the iron and oxygen field in 2012, and was awarded a four-year British Heart Foundation Intermediate Basic Science Research Fellowship. In 2019, I was elected to the Board of Directors of the Internal BioIron Society. My current work focuses on dissecting iron regulation in the heart, the kidney, the placenta and the vasculature, by utilising novel animal models of tissue-specific alterations in iron metabolism.
In 2020, I was awarded an MRC Senior Non-Clinical Research Fellowship, to address the clinical implications of local iron control in the setting of chronic heart failure.
Recent publications
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Intravenous iron therapy results in rapid and sustained rise in myocardial iron content through a novel pathway.
Journal article
Vera-Aviles M. et al, (2024), Eur Heart J
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Iron deficiency and supplementation in heart failure
Journal article
Lakhal-Littleton S. and Cleland JGF., (2024), Nature Reviews Cardiology
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Low Serum Ferritin Might Predict Incident Heart Failure
Journal article
Cleland JGF. et al, (2024), JACC: Heart Failure
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The complex relationship between iron status and anemia in pregnant and postpartum women in India: analysis of two Indian study cohorts of uncomplicated pregnancies
Journal article
NAIR M. et al, (2023), American Journal of Hematology
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Protective Role for Smooth Muscle Cell Hepcidin in Abdominal Aortic Aneurysm.
Journal article
Loick P. et al, (2023), Arterioscler Thromb Vasc Biol
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Minimal effect of conditional ferroportin KO in the neural retina implicates ferrous iron in retinal iron overload and degeneration.
Journal article
Liu Y. et al, (2022), Exp Eye Res, 218
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Hepcidin sequesters iron to sustain nucleotide metabolism and mitochondrial function in colorectal cancer epithelial cells.
Journal article
Schwartz AJ. et al, (2021), Nat Metab, 3, 969 - 982
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Maternal iron deficiency perturbs embryonic cardiovascular development in mice
Journal article
SPARROW D. et al, (2021), Nature Communications