Research groups
Colleges
Samira Lakhal-Littleton
Associate Professor of Physiology and MRC Senior Non-Clinical Research Fellow
- Principal Investigator
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.
Key publications
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Intracellular iron deficiency in pulmonary arterial smooth muscle cells induces pulmonary arterial hypertension in mice.
Journal article
Lakhal-Littleton S. et al, (2019), Proc Natl Acad Sci U S A, 116, 13122 - 13130
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The interplay between iron and oxygen homeostasis with a particular focus on the heart.
Journal article
Lakhal-Littleton S. and Robbins PA., (2017), J Appl Physiol (1985), 123, 967 - 973
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An essential cell-autonomous role for hepcidin in cardiac iron homeostasis.
Journal article
Lakhal-Littleton S. et al, (2016), Elife, 5
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Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function.
Journal article
Lakhal-Littleton S. et al, (2015), Proc Natl Acad Sci U S A, 112, 3164 - 3169
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Induced Disruption of the Iron-Regulatory Hormone Hepcidin Inhibits Acute Inflammatory Hypoferraemia.
Journal article
Armitage AE. et al, (2016), J Innate Immun, 8, 517 - 528
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Regulation of hepcidin expression at high altitude.
Journal article
Talbot NP. et al, (2012), Blood, 119, 857 - 860
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Regulation of type II transmembrane serine proteinase TMPRSS6 by hypoxia-inducible factors: new link between hypoxia signaling and iron homeostasis.
Journal article
Lakhal S. et al, (2011), J Biol Chem, 286, 4090 - 4097
Recent publications
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Fetal liver hepcidin secures iron stores in utero.
Journal article
Kämmerer L. et al, (2020), Blood, 136, 1549 - 1557
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Dendritic cell-derived hepcidin sequesters iron from the microbiota to promote mucosal healing.
Journal article
Bessman NJ. et al, (2020), Science, 368, 186 - 189
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Ferroportin-mediated iron export from vascular endothelial cells in retina and brain.
Journal article
Baumann BH. et al, (2019), Exp Eye Res, 187
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Liver-Specific, but Not Retina-Specific, Hepcidin Knockout Causes Retinal Iron Accumulation and Degeneration.
Journal article
Baumann BH. et al, (2019), Am J Pathol, 189, 1814 - 1830
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Iron Deficiency as a Therapeutic Target in Cardiovascular Disease.
Journal article
Lakhal-Littleton S., (2019), Pharmaceuticals (Basel), 12
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IMPACTS OF MATERNAL IRON DEFICIENCY ON THE MOUSE PLACENTAL-HEART AXIS
Conference paper
Kalisch-Smith J. et al, (2019), PLACENTA, 83, E47 - E48
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Ferroportin promotes iron import through the retinal vascular endothelium
Conference paper
Shu W. et al, (2019), INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 60