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| Name |
| Arezes, João |
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| Nationality |
| Portuguese |
| E-Mail |
| jtarezes@gmail.com |
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| 1st Degree |
| Biochemistry |
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| University (1st Degree) |
| Porto |
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| Master Degree |
| Biochemistry |
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| University (Master Degree) |
| Porto |
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| About the PhD |
| Field of Research |
| Iron Biology / Infection |
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| Thesis Title |
| The role of hepcidin in host defense against Vibrio vulnificus infections |
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| Abstract |
| Hereditary hemochromatosis, an iron overload disease caused by a deficiency in the iron-regulatory hormone hepcidin, is associated with lethal infections by siderophilic bacteria. To elucidate the mechanisms of this susceptibility,... |
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| Hereditary hemochromatosis, an iron overload disease caused by a deficiency in the iron-regulatory hormone hepcidin, is associated with lethal infections by siderophilic bacteria. To elucidate the mechanisms of this susceptibility, we infected wild-type and hepcidin-deficient mice with the siderophilic bacterium Vibrio vulnificus and found that hepcidin deficiency results in increased bacteremia and decreased survival of infected mice, which can be partially ameliorated by dietary iron depletion. Additionally, timely administration of hepcidin agonists to hepcidin-deficient mice induces hypoferremia that decreases bacterial loads and rescues these mice from death, regardless of initial iron levels. Studies of Vibrio vulnificus growth ex vivo show that high iron sera from hepcidin-deficient mice support extraordinarily rapid bacterial growth and that this is inhibited in hypoferremic sera. Our findings demonstrate that hepcidin-mediated hypoferremia is a host defense mechanism against siderophilic pathogens and suggest that hepcidin agonists may improve infection outcomes in patients with hereditary hemochromatosis or thalassemia. |
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| Supervisor(s) |
| Elizabeta Nemeth, PhD |
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| Co-Supervisor(s) |
| Tomas Ganz, MD, PhD; Graça Porto, MD, PhD |
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| University |
| University of California, Los Angeles |
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| City |
| Los Angeles |
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| Country |
| USA |
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| Date of Thesis Defence |
| 2015-11-20 |
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| After the PhD (Current Situation) |
| Position |
| Postdoctoral Scientist |
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| Institution |
| Weatherall Institute of Molecular Medicine, University of Oxford |
| View Institution website |
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| City |
| Oxford |
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| Country |
| United kingdom |
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| Relevant Publications |
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| Hepcidin-Induced Hypoferremia Is a Critical Host Defense Mechanism against the Siderophilic Bacterium Vibrio vulnificus, Cell Host & Microbe, 2015, 17, 47-57 |
| View Publication |
| Publications |
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| Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Aquisition of Oligomeric Ferric Citrate Species, PLOS One, 2013, 8(11):e79870 |
| View Publication |
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| Physiological implications of NTBI uptake by T lymphocytes, Frontiers in Pharmacology, 2014, 5:24 |
| View Publication |
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| Hepcidin and iron disorders: new biology and clinical approaches, International Journal of Laboratory Hematology, 2015, |
| View Publication |
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| Endogenous hepcidin and its agonist mediate resistance to selected infections by clearing non–transferrin-bound iron, Blood 2017 130:245-257 |
| View Publication |
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| Hepcidin is regulated by promoter-associated histone acetylation and HDAC3, Nature Communications 8, Article number: 403 (2017) |
| View Publication |
| Last Update |
| 2017-10-11 16:01:44 |
| The responsibility for this page contents is entirely of the student/alumnus. |
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Program financially supported by
the National Foundation for
Science and Technology
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