Basic & Clinical Research on Iron Biology
ABOUT

Iron Biology stands as a fast growing field of knowledge, spanning from the basic understanding of cell and systems homeostasis to applications in most medical fields. The BCRIB fits the model of a “translational research” group where scientists involved in fundamental research cooperate intimately with practicing clinicians potentiating the group’s capacity to elucidate basic principles of iron biology and put forward new approaches to address iron-related disorders.

RESEARCH

Achievements:

Focusing on the reciprocal interactions between iron, inflammation and immunity, we generated knowledge that may ultimately improve the management of iron-related disorders, in particular hereditary hemochromatosis (HH), a MHC class I-linked genetic disease with high prevalence in Portugal. We found novel associations of lymphocyte and iron phenotypes with particular MHC-linked microhaplotypes, as well as abnormal effector memory CD8+ T cells and increased expression of calprotectin S100A9 in HH patients. We demonstrated that T cells are able to take up non-transferrin-bound iron, thus acting as circulating “buffers” against systemic iron toxicity. This finding offered a first mechanistic explanation for the previously described association of iron overload with defective numbers of circulating CD8+ T cells in HH patients. In mouse models of HH, we found that the antioxidant response coordinated by transcription factor Nrf2 is essential for protecting the liver against iron toxicity. We also investigated the role of stromal lymphocytes in breast cancer, and proposed a role for lymphocytes as iron donor cells in the transition of in situ to invasive carcinoma. We are part of a clinical and research integrated centre for HH (with the Hematology Service at CHP-Hospital Santo António and the Centre for Predictive and Preventive Genetics, CGPP) that integrated the European Reference Network on Rare Hematological Disorders (EuroBloodNet) in 2017.

Ongoing projects:

• further explore the association between genetics of MHC and lymphocyte numbers, and approach evolutionary aspects of the HFE mutations;

• identify novel genetic and environmental modifiers of disease expression in HH acting either as modifiers of body iron levels or as modifiers of the cellular response to iron-induced stress;

• determine the impact of extracellular iron on cartilage stability in the context of HH arthropathy.

Energy dispersive X-ray (EDX) elemental analysis showing Iron (Fe, green) accumulation in a carbon-rich (C, red) intracellular region of a human monocyte