A5083448140- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
- Trace Elements in Health
- Erythrocyte Function and Pathophysiology
- Erythropoietin and Anemia Treatment
- Bone health and treatments
- Vibrio bacteria research studies
- RNA modifications and cancer
- Hepatitis B Virus Studies
- Business and Management Studies
- Multiple Myeloma Research and Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Liver Disease Diagnosis and Treatment
MRC Weatherall Institute of Molecular Medicine
2017-2020
University of Oxford
2016-2020
John Radcliffe Hospital
2018-2020
MRC Human Immunology Unit
2017-2020
Medical Research Council
2017-2018
Universidade do Porto
2013-2015
University of California, Los Angeles
2015
BackgroundHow specific nutrients influence adaptive immunity is of broad interest. Iron deficiency the most common micronutrient worldwide and imparts a significant burden global disease; however, its effects on remain unclear.MethodsWe used hepcidin mimetic several genetic models to examine effect low iron availability T cells in vitro immune responses vaccines viral infection mice. We examined humoral human patients with raised serum caused by mutant TMPRSS6. tested supplementation...
Hepcidin regulates systemic iron homeostasis. Suppression of hepcidin expression occurs physiologically in deficiency and increased erythropoiesis but is pathologic thalassemia hemochromatosis. Here we show that epigenetic events govern expression. Erythropoiesis suppress via erythroferrone-dependent -independent mechanisms, respectively, vivo, both involve reversible loss H3K9ac H3K4me3 at the locus. In vitro, pan-histone deacetylase inhibition elevates expression, vivo maintains...
Abstract Multiple myeloma is an incurable, bone marrow-dwelling malignancy that disrupts homeostasis causing skeletal damage and pain. Mechanisms underlying myeloma-induced destruction are poorly understood current therapies do not restore lost mass. Using transcriptomic profiling of isolated lining cell subtypes from a murine model, we find morphogenetic protein (BMP) signalling upregulated in stromal progenitor cells. BMP has previously been reported to be dysregulated disease. Inhibition...
In iron overload disorders a significant fraction of circulates in the plasma as low molecular weight complexes not bound to transferrin, known non-transferrin-bound (NTBI). By catalyzing formation free radicals, NTBI accumulation results oxidative stress and cellular damage causing organ toxicity. is rapidly preferentially cleared from circulation by liver myocardium, main disease targets conditions. We have recently demonstrated that human peripheral blood T lymphocytes take up vitro, with...
Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In overload disorders, however, concentrations exceed transferrin binding capacity appears complexed with low molecular weight molecules, known non-transferrin-bound (NTBI). NTBI responsible for the toxicity associated iron-overload pathologies but mechanisms leading uptake are not fully understood. Here we show...