Dr Samira Lakhal-Littleton
Contact information
| samira.lakhal-littleton@dpag.ox.ac.uk | |
| Tel | 01865 272543 |
Samira Lakhal-Littleton
BHF Intermediate Basic Science Research Fellow and University Research Lecturer
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 two-year stint in the exciting field of exosome nanotechnology, I returned to the iron and oxygen field in 2012, and was awarded a four-year British Heart Foundation Intermediate Basic Science Research Fellowship. 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.
Key Publications
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Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function.
Lakhal-Littleton S. et al, (2015), Proc Natl Acad Sci U S A, 112, 3164 - 3169
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Regulation of hepcidin expression at high altitude.
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.
Lakhal S. et al, (2011), J Biol Chem, 286, 4090 - 4097
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Regulation of growth differentiation factor 15 expression by intracellular iron.
Lakhal S. et al, (2009), Blood, 113, 1555 - 1563
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Hepcidin demonstrates a biphasic association with anemia in acute Plasmodium falciparum malaria.
Casals-Pascual C. et al, (2012), Haematologica, 97, 1695 - 1698
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IDO induces expression of a novel tryptophan transporter in mouse and human tumor cells
Silk JD. et al, (2011), Journal of Immunology, 187, 1617 - 1625
Recent Publications
20-
An essential cell-autonomous role for hepcidin in cardiac iron homeostasis.
Lakhal-Littleton S. et al, (2016), Elife, 5
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Suppression of plasma hepcidin by venesection during steady-state hypoxia.
Talbot NP. et al, (2016), Blood, 127, 1206 - 1207
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IRON-DEPENDENT EPIGENETIC REGULATION BY THE HISTONE DEMETHYLASE KDM4A IN THE HEART
Chung YJ. et al, (2016), AMERICAN JOURNAL OF HEMATOLOGY, 91, E193 - E193
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Induced Disruption of the Iron-Regulatory Hormone Hepcidin Inhibits Acute Inflammatory Hypoferraemia.
Armitage AE. et al, (2016), J Innate Immun, 8, 517 - 528
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Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function.
Lakhal-Littleton S. et al, (2015), Proc Natl Acad Sci U S A, 112, 3164 - 3169
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THE ROLES OF HEPCIDIN AND FERROPORTIN IN AUTOCRINE REGULATION OF IRON LEVELS
Lakhal-Littleton S. et al, (2013), AMERICAN JOURNAL OF HEMATOLOGY, 88, E49 - E49
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Exosomes for targeted siRNA delivery across biological barriers
EL Andaloussi S. et al, (2013), Advanced Drug Delivery Reviews, 65, 391 - 397
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Exosomes for targeted siRNA delivery across biological barriers.
El Andaloussi S. et al, (2013), Adv Drug Deliv Rev, 65, 391 - 397
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Exosome-mediated delivery of siRNA in vitro and in vivo.
El-Andaloussi S. et al, (2012), Nat Protoc, 7, 2112 - 2126
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Hepcidin demonstrates a biphasic association with anemia in acute Plasmodium falciparum malaria.
Casals-Pascual C. et al, (2012), Haematologica, 97, 1695 - 1698
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Microvesicles and exosomes: Opportunities for cell-derived membrane vesicles in drug delivery
Van Dommelen SM. et al, (2012), Journal of Controlled Release, 161, 635 - 644
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Microvesicles and exosomes: opportunities for cell-derived membrane vesicles in drug delivery.
van Dommelen SM. et al, (2012), J Control Release, 161, 635 - 644
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Regulation of hepcidin expression at high altitude.
Talbot NP. et al, (2012), Blood, 119, 857 - 860
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Intranasal exosomes for treatment of neuroinflammation? Prospects and limitations.
Lakhal S. and Wood MJ., (2011), Mol Ther, 19, 1754 - 1756
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Exosome nanotechnology: an emerging paradigm shift in drug delivery: exploitation of exosome nanovesicles for systemic in vivo delivery of RNAi heralds new horizons for drug delivery across biological barriers.
Lakhal S. and Wood MJ., (2011), Bioessays, 33, 737 - 741
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Delivery of siRNA to the brain by systemic injection of targeted exosomes
Alvarez-Erviti L. et al, (2011), HUMAN GENE THERAPY, 22, A42 - A42
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Exosomes and the blood-brain barrier: implications for neurological diseases.
Wood MJ. et al, (2011), Ther Deliv, 2, 1095 - 1099
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IDO induces expression of a novel tryptophan transporter in mouse and human tumor cells
Silk JD. et al, (2011), Journal of Immunology, 187, 1617 - 1625
-
IDO induces expression of a novel tryptophan transporter in mouse and human tumor cells.
Silk JD. et al, (2011), J Immunol, 187, 1617 - 1625
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Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes.
Alvarez-Erviti L. et al, (2011), Nat Biotechnol, 29, 341 - 345